Trial Outcomes & Findings for METIMMOX: Colorectal Cancer METastasis - Shaping Anti-tumor IMMunity by OXaliplatin (NCT NCT03388190)
NCT ID: NCT03388190
Last Updated: 2026-02-13
Results Overview
To determine PFS, in terms of failure of treatment strategy, on sequential treatment with the Nordic FLOX regimen and nivolumab compared with the standard-of-care Nordic FLOX regimen in previously untreated MSS mCRC. \*PFS: radiologic assessment every 8 weeks (following 4 cycles of FLOX or the alternative 2 cycles each of FLOX and nivolumab), according to the Response Evaluation Criteria in Solid Tumors (RECIST) and the RECIST consensus guideline for assessment of response to immune-modulating therapies (iRECIST), wherein complete response = disappearance of the lesion, partial response = at least a 30% decrease in the sum of diameters of target lesions, progressive disease = at least 20% increase in the sum of diameters of target lesions, and stable disease = no shrinkage or increase in size (per Watanabe H, Okada M, Kaji Y, et al. Gan To Kagaku Ryoho. 2009;36(13):2495-2501).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
80 participants
Primary outcome timeframe
Through study completion (up to 37 months)
Results posted on
2026-02-13
Participant Flow
Participant milestones
| Measure |
Control Arm
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
38
|
38
|
|
Overall Study
COMPLETED
|
38
|
38
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Control Arm
n=38 Participants
The control arm will consist of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy is reintroduced and administered for another 8 cycles before a new break. This schedule will be continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=38 Participants
The experimental arm will consist of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy is reintroduced and administered for another total of 8 individual cycles before a new break. This schedule will be continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
Total
n=76 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.0 years
n=38 Participants
|
60.5 years
n=38 Participants
|
64.5 years
n=76 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=38 Participants
|
20 Participants
n=38 Participants
|
35 Participants
n=76 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=38 Participants
|
18 Participants
n=38 Participants
|
41 Participants
n=76 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: Through study completion (up to 37 months)To determine PFS, in terms of failure of treatment strategy, on sequential treatment with the Nordic FLOX regimen and nivolumab compared with the standard-of-care Nordic FLOX regimen in previously untreated MSS mCRC. \*PFS: radiologic assessment every 8 weeks (following 4 cycles of FLOX or the alternative 2 cycles each of FLOX and nivolumab), according to the Response Evaluation Criteria in Solid Tumors (RECIST) and the RECIST consensus guideline for assessment of response to immune-modulating therapies (iRECIST), wherein complete response = disappearance of the lesion, partial response = at least a 30% decrease in the sum of diameters of target lesions, progressive disease = at least 20% increase in the sum of diameters of target lesions, and stable disease = no shrinkage or increase in size (per Watanabe H, Okada M, Kaji Y, et al. Gan To Kagaku Ryoho. 2009;36(13):2495-2501).
Outcome measures
| Measure |
Control Arm
n=38 Participants
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=38 Participants
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Primary - Progression-free Survival (PFS)
|
9.2 Months of progression-free survival
Interval 6.3 to 12.7
|
9.2 Months of progression-free survival
Interval 4.5 to 15.0
|
SECONDARY outcome
Timeframe: Through study completion (up to 37 months)To determine the number of participants (incidence; safety) with treatment-related adverse events and their grading (tolerability), as assessed by CTCAE v4.0, of sequential treatment with the Nordic FLOX regimen and nivolumab compared with the standard-of-care Nordic FLOX regimen. A lower adverse event score is better, where a score of 0 is best (no adverse event), 3 is severe, and 5 is death caused by the treatment. Stage 2 adverse events were not specifically reported unless related to hepatic toxicity events due to the potential effects of the drug on the patient (safety profile).
Outcome measures
| Measure |
Control Arm
n=38 Participants
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=38 Participants
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Secondary 1 - Incidence (Safety) and Grading (Tolerability) of Treatment-related Adverse Events
Patients displaying a Grade 2 Adverse Event
|
0 participants showing an adverse event
|
2 participants showing an adverse event
|
|
Secondary 1 - Incidence (Safety) and Grading (Tolerability) of Treatment-related Adverse Events
Patients displaying a Grade 3 Adverse Event
|
26 participants showing an adverse event
|
37 participants showing an adverse event
|
|
Secondary 1 - Incidence (Safety) and Grading (Tolerability) of Treatment-related Adverse Events
Patients displaying a Grade 4 Adverse Event
|
10 participants showing an adverse event
|
11 participants showing an adverse event
|
SECONDARY outcome
Timeframe: Through study completion (up to 37 months)Population: ORR for experimental arm 17/36 (47%) versus 20/31 (65%) in control arm, p=0.16.
To determine the percentage of patients with confirmed complete or partial response of sequential treatment with the Nordic FLOX regimen and nivolumab compared with the standard-of-care Nordic FLOX regimen.
Outcome measures
| Measure |
Control Arm
n=31 Participants
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=36 Participants
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Secondary 2 - Objective Response Rate (ORR)
|
20 Participants
|
17 Participants
|
SECONDARY outcome
Timeframe: Through study completion (up to 37 months)To determine the time from the first documentation of a complete or partial response to disease progression of sequential treatment with the Nordic FLOX regimen and nivolumab compared with the standard-of-care Nordic FLOX regimen.
Outcome measures
| Measure |
Control Arm
n=38 Participants
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=38 Participants
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Secondary 3 - Duration of Response (DOR)
|
9.0 Months with durable response
Interval 2.0 to 11.0
|
15.0 Months with durable response
Interval 7.0 to 18.0
|
SECONDARY outcome
Timeframe: Through study completion (up to 37 months)Population: Number of patients who underwent secondary curative resection (surgery to excise metastases)
To determine the percentage of patients with a confirmed resection of metastatic disease with microscopically free margin (R0) of sequential treatment with the Nordic FLOX regimen and nivolumab compared with the standard-of-care Nordic FLOX regimen.
Outcome measures
| Measure |
Control Arm
n=38 Participants
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=38 Participants
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Secondary 4 - Secondary Curative Resection Rate (SSCRR)
|
5 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Through study completion (up to 37 months)To determine the time from randomization to death of any cause of sequential treatment with the Nordic FLOX regimen and nivolumab compared with the standard-of-care Nordic FLOX regimen.
Outcome measures
| Measure |
Control Arm
n=38 Participants
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=38 Participants
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Secondary 5 - Overall Survival (OS)
|
14.6 Months
Interval 10.6 to 23.2
|
20.7 Months
Interval 15.9 to 24.9
|
SECONDARY outcome
Timeframe: Through study completion (up to 37 months)To monitor and compare QoL alterations during therapy courses using the consensus module EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life, 30 question version). The (patient-reported) EORTC-QLQ-C30 uses 5 functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea and vomiting), a global health status/quality of life scale and a number of other questions which assess items such as dyspnoea, loss of appetite, insomnia, constipation and diarrhoea, as well as the perceived financial impact of having cancer. Scales range from 0 to 100, and a higher score means a higher response rate, where a high score on the functional or global health status questions represents a high or healthy level of functioning, quality of life or, alternatively, more symptoms or issues (symptom scale/items). \[Scoring information summarised from the EORTC QLQ-C30 Scoring manual, 3rd edition\]
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion (up to 37 months)To monitor and compare QoL alterations during therapy courses using the consensus module EORTC QLQ-CIPN20 (European Organisation for Research and Treatment of Cancer Quality of Life, 20 question Chemotherapy Induced Peripheral Neuropathy questionnaire). The EORTC QLQ-CIPN20 uses 20 questions assessing the quality of sensory, motor and autonomic symptoms on a 4-point Likert scale. Answers range from 1 (not at all) to 4 (very much). Patients indicate their perception of each item, and the scores are aggregated by quality, with a maximum of 32 points for motor, 36 for sensory, and either 12 (men) or 8 (women) in autonomic, where women would not answer a question about erectile function. Scores are then added together to give an overall score. The higher the score, the more symptoms the patient is experiencing.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion (up to 37 months)To monitor and compare QoL alterations during therapy courses using the consensus module EQ-5D-5L (EuroQoL's 5-dimension, 5-level questionnaire). The EQ-5D-5L questionnaire is a "standardised measure of health status developed by the EuroQol group to provide a simple, generic measure of health for clinical and economic appraisal". The questionnaire uses 5 dimensions (5D) - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. There are 5 response levels: no issues, slight problems, moderate problems, severe problems and unable to function/extreme problems. These answers are geared appropriately to the specific question being asked. Responses are coded from 0 for no problems to 5 for unable to function, and are combined to give a 5-digit code that will describe the patient's state of health. For example, 21111 would mean slight problems with mobility, but no other issues in the other dimensions. (summarised from the EQ-5D-5L user guide, v3.0).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Through study completion (up to 37 months)To compare costs for the resource use (in diagnostic work-up, treatment, and any adverse events) for the sequential therapy with that of the standard-of-care, applying a model specifically developed for CRC.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Through study completion (up to 37 months)Population: Data not collected; Due to the COVID pandemic we could not collect enough samples.
To monitor the individual patients' levels of PTEN (phosphatase and tensin homolog) phosphatase activity in peripheral blood mononuclear cells throughout study treatment.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Through study completion (maximum of 37 months)Population: Individuals dropping out either withdrew consent or died from their disease. During treatment patients were seen every two weeks, with blood samples drawn for experimental purposes every other visit; off treatment, they were seen every two months, with blood samples taken at those visits.
To monitor the individual patients' levels of plasma tumor DNA throughout study treatment. Measure is variant allele frequency (VAF, in %) relative to baseline.
Outcome measures
| Measure |
Control Arm
n=9 Participants
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=3 Participants
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
Baseline Visit (Time of Inclusion, before start of treatment)
|
77.8 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 100.0
|
66.7 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 100.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
1 Month after first treatment
|
92.5 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 221.9
|
2.3 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 6.8
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
2 months after first treatment
|
97.9 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 400.5
|
0.6 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 1.75
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
3 months after first treatment
|
46.2 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 110.4
|
1.7 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 5.23
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
4 months after first treatment
|
46.2 Variant Allele Frequency (VAF, in %)
Interval 4.0 to 100.0
|
3.7 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 8.1
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
6 months after first treatment
|
—
|
8.0 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 24.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
8 months after first treatment
|
—
|
0.9 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 2.56
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
10 months after first treatment
|
—
|
0 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 0.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
12 months after first treatment
|
—
|
0.0 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 0.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
14 months after first treatment
|
—
|
3.6 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 10.9
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
16 months after first treatment
|
—
|
0.0 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 0.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
18 months after first treatment
|
—
|
0.0 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 0.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
20 months after first treatment
|
—
|
1.4 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 4.2
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
22 months after first treatment
|
—
|
15.7 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 31.4
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
23 months after first treatment
|
—
|
1.5 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 2.9
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
24 months after first treatment
|
—
|
20.3 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 41.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
25 months after first treatment
|
—
|
0.0 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 0.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
26 months after first treatment
|
—
|
0.0 Variant Allele Frequency (VAF, in %)
Interval 0.0 to 0.0
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
28 months after first treatment
|
—
|
0.2 Variant Allele Frequency (VAF, in %)
Interval 0.2 to 0.2
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
29 months after first treatment
|
—
|
3.5 Variant Allele Frequency (VAF, in %)
Interval 3.5 to 3.5
|
|
Exploratory 2 - Circulating Biomarkers of Tumor Response
30 months after first treatment
|
—
|
1.1 Variant Allele Frequency (VAF, in %)
Interval 1.1 to 1.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Through study completion (maximum of 37 months)Measures of circulating immune factors and T cell phenotypes in serial serum/plasma/whole blood samples collected corresponding to each change of therapy in the sequential regimen.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Through study completion (up to 37 months)To monitor the individual patients' changes in liver/peritoneal functional MR signals throughout study treatment. The COVID pandemic stopped the collection of data for this trial due to lack of available staff and equipment, as well as analysts. Therefore, no data will be presented for this outcome.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Through study completion (month 37)Population: Only one participant's samples were analysed due to patients declining to participate. Liver and peritoneal metastatic tumor tissue samples were taken at several timepoints during one experimental patient's treatment.
To monitor the individual patients' changes in liver/peritoneal tissue composition throughout study treatment.
Outcome measures
| Measure |
Control Arm
n=1 Participants
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Exploratory 5 - Histologic and Molecular Tumor Biomarkers
At Baseline (Apr 2019)
|
22185 Number of T-cell receptor sequences
|
—
|
|
Exploratory 5 - Histologic and Molecular Tumor Biomarkers
At time of 1st relapse surgery (Jan 2021)
|
82263 Number of T-cell receptor sequences
|
—
|
|
Exploratory 5 - Histologic and Molecular Tumor Biomarkers
At time of 2nd relapse surgery (Nov 2021)
|
7252 Number of T-cell receptor sequences
|
—
|
Adverse Events
Control Arm
Serious events: 35 serious events
Other events: 0 other events
Deaths: 33 deaths
Experimental Arm
Serious events: 32 serious events
Other events: 2 other events
Deaths: 34 deaths
Serious adverse events
| Measure |
Control Arm
n=38 participants at risk
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=38 participants at risk
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Cardiac disorders
Cardiac asystole
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Cardiac disorders
Dehydration
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Cardiac disorders
Edema
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Cardiac disorders
Arterial hypertension
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Gastrointestinal disorders
Diarrhea
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
7.9%
3/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Gastrointestinal disorders
Ileus
|
7.9%
3/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
7.9%
3/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Gastrointestinal disorders
Nausea
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Blood and lymphatic system disorders
Anemia
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
18.4%
7/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Blood and lymphatic system disorders
Neutropenia
|
57.9%
22/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
39.5%
15/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Blood and lymphatic system disorders
Venous thromboembolism
|
10.5%
4/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
18.4%
7/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Infections and infestations
Fever
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Infections and infestations
Infection
|
13.2%
5/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
13.2%
5/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Nervous system disorders
Fatigue
|
10.5%
4/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
7.9%
3/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Nervous system disorders
Pain
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Nervous system disorders
Paresthesia
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Nervous system disorders
Spinal cord compression
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Renal and urinary disorders
Renal failure
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Product Issues
Infusion-related reaction
|
5.3%
2/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Immune system disorders
Arthritis
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Immune system disorders
Hyperglycaemia
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
10.5%
4/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Immune system disorders
Hypophysitis
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Immune system disorders
Increased hepatic enzymes
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
10.5%
4/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Immune system disorders
Pneumonitis
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
2.6%
1/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
|
Immune system disorders
Rash
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
7.9%
3/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
Other adverse events
| Measure |
Control Arm
n=38 participants at risk
The control arm consisted of intermittent treatment with the Nordic FLOX regimen in terms of 8 cycles before break until disease progression, when therapy was reintroduced and administered for another 8 cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occured first.
FLOX: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
|
Experimental Arm
n=38 participants at risk
The experimental arm consisted of repeat 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 8 individual cycles before break until disease progression, when therapy was reintroduced and administered for another total of 8 individual cycles before a new break. This schedule was continued until progressive disease on ongoing therapy (PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.
Nivolumab: FLOX: Intravenous oxaliplatin 85 mg/m2 on day 1; bolus 5-fluorouracil 500 mg/m2 and bolus Leucovorin on days 1 and 2; IV administration every 2 weeks.
Nivolumab: 240 mg flat dose; IV administration every 2 weeks.
|
|---|---|---|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, Increased hepatic enzymes
|
0.00%
0/38 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
5.3%
2/38 • Number of events 2 • All patients were monitored for any adverse events throughout the trial and for 1 year after study completion (up to 37 months).
Definitions do not differ from the clinicaltrials.gov definition.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place