Trial Outcomes & Findings for Chemotherapy for Patients With Osteosarcoma (NCT NCT00523419)
NCT ID: NCT00523419
Last Updated: 2011-06-28
Results Overview
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) = at least a 20% increase in sum of longest diameter of target lesions; Stable Disease (SD) = small changes that do not meet above criteria. Tumor Response Rate(%) = sum of number of PR + CR observed/number of participants qualified for tumor response analysis \* 100.
COMPLETED
PHASE2
32 participants
Baseline to 21 months
2011-06-28
Participant Flow
Participant milestones
| Measure |
Pemetrexed
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Overall Study
STARTED
|
32
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
32
|
Reasons for withdrawal
| Measure |
Pemetrexed
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
Progressive Disease
|
22
|
|
Overall Study
Death due to Study Disease
|
4
|
|
Overall Study
Death due to Adverse Event
|
2
|
Baseline Characteristics
Chemotherapy for Patients With Osteosarcoma
Baseline characteristics by cohort
| Measure |
Pemetrexed
n=32 Participants
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Age Continuous
|
42.1 years
STANDARD_DEVIATION 16.28 • n=99 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=99 Participants
|
|
Region of Enrollment
France
|
13 participants
n=99 Participants
|
|
Region of Enrollment
Spain
|
3 participants
n=99 Participants
|
|
Region of Enrollment
Germany
|
6 participants
n=99 Participants
|
|
Region of Enrollment
United Kingdom
|
1 participants
n=99 Participants
|
|
Region of Enrollment
Italy
|
9 participants
n=99 Participants
|
|
Best Response of Last Prior Treatment Regimen for Osteosarcoma
Complete Response
|
1 participants
n=99 Participants
|
|
Best Response of Last Prior Treatment Regimen for Osteosarcoma
Partial Response
|
3 participants
n=99 Participants
|
|
Best Response of Last Prior Treatment Regimen for Osteosarcoma
Stable Disease
|
10 participants
n=99 Participants
|
|
Best Response of Last Prior Treatment Regimen for Osteosarcoma
Progressive Disease
|
15 participants
n=99 Participants
|
|
Best Response of Last Prior Treatment Regimen for Osteosarcoma
Not Applicable
|
3 participants
n=99 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status
ECOG Performance Status 0
|
16 participants
n=99 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status
ECOG Performance Status 1
|
14 participants
n=99 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status
ECOG Performance Status 2
|
1 participants
n=99 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) performance status
ECOG Performance Status Not Available
|
1 participants
n=99 Participants
|
|
Histopathological Diagnosis of Osteosarcoma at Study Entry
|
32 participants
n=99 Participants
|
|
Number of Target Lesions
0 Target Lesions
|
1 participants
n=99 Participants
|
|
Number of Target Lesions
1 Target Lesion
|
9 participants
n=99 Participants
|
|
Number of Target Lesions
2 Target Lesions
|
8 participants
n=99 Participants
|
|
Number of Target Lesions
3 Target Lesions
|
4 participants
n=99 Participants
|
|
Number of Target Lesions
4 Target Lesions
|
3 participants
n=99 Participants
|
|
Number of Target Lesions
5 Target Lesions
|
7 participants
n=99 Participants
|
|
Number of non target lesions
0 Non Target Lesions
|
10 participants
n=99 Participants
|
|
Number of non target lesions
1 Non Target Lesion
|
15 participants
n=99 Participants
|
|
Number of non target lesions
2 Non Target Lesions
|
5 participants
n=99 Participants
|
|
Number of non target lesions
3 Non Target Lesions
|
1 participants
n=99 Participants
|
|
Number of non target lesions
5 Non Target Lesions
|
1 participants
n=99 Participants
|
|
Pathological Diagnosis of Osteosarcoma at Study Entry
|
32 participants
n=99 Participants
|
|
Time from last diagnosis to enrollment
|
13.3 days
STANDARD_DEVIATION 12.10 • n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline to 21 monthsPopulation: Participants who qualified for tumor response analysis are those with histological evidence of high grade locally advanced or metastatic osteosarcoma and treatment with at least 1 dose of study drug. Three participants died before the first tumor assessment and 1 participant discontinued without any tumor assessments and were considered Unknown.
Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) = at least a 20% increase in sum of longest diameter of target lesions; Stable Disease (SD) = small changes that do not meet above criteria. Tumor Response Rate(%) = sum of number of PR + CR observed/number of participants qualified for tumor response analysis \* 100.
Outcome measures
| Measure |
Pemetrexed
n=32 Participants
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Percentage of Participants With Tumor Response
Progressive Disease (PD)
|
68.8 percentage of participants
Interval 50.0 to 83.9
|
|
Percentage of Participants With Tumor Response
Unknown
|
12.5 percentage of participants
Interval 3.5 to 29.0
|
|
Percentage of Participants With Tumor Response
Response Rate
|
3.1 percentage of participants
Interval 0.1 to 16.2
|
|
Percentage of Participants With Tumor Response
Complete Response (CR)
|
0 percentage of participants
Interval 0.0 to 0.0
|
|
Percentage of Participants With Tumor Response
Partial Response (PR)
|
3.1 percentage of participants
Interval 0.1 to 16.2
|
|
Percentage of Participants With Tumor Response
Stable Disease (SD)
|
15.6 percentage of participants
Interval 5.3 to 32.8
|
SECONDARY outcome
Timeframe: Baseline to 21 monthsPopulation: Since this outcome measure was not analyzed due to the study design, zero participants were analyzed.
When the protocol was written, time to treatment failure (TTTF) was included as a secondary endpoint. However, it was subsequently realized that due to the design of the study, participants are treated until disease progression or discontinuation from study treatment, not for a fixed number of cycles. Therefore, it was concluded that analysis of TTTF was inappropriate with the current study design and the analysis was not conducted, since it would be essentially the same as Progression-Free Survival.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to 21 monthsPopulation: Since this outcome measure was not analyzed due to the inadequate number of responders, zero participants were analyzed.
It was planned to examine methylthioadenosine phosphorylase (MTAP) gene deletion, folate receptor alpha (FRα) and folylpoly-gamma-glutamate synthetase (FPGS) expression, and to correlate the results with the clinical data to determine the association between these factors and clinical outcome to treatment. However, due to the small number of participants with partial response (n=1), the planned statistical analyses that would correlate responders/non responders with pharmacogenomics data are no longer valid and the analyses were not conducted.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to 21 monthsPopulation: Full analysis population: all participants who were treated with at least one dose of the study regimen
Pharmacology toxicity was defined as serious and non-serious adverse events. Summaries of these adverse events are located in the Reported Adverse Event Section.
Outcome measures
| Measure |
Pemetrexed
n=32 Participants
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Number of Participants With Adverse Events (Pharmacology Toxicity)
Serious Adverse Events
|
11 participants
|
|
Number of Participants With Adverse Events (Pharmacology Toxicity)
All Other Nonserious Adverse Events
|
26 participants
|
SECONDARY outcome
Timeframe: Baseline to 31 monthsPopulation: Tumor response population: participants with best overall response of complete response (CR) and partial response (PR).
The duration of a complete response (CR) or partial response (PR) was defined as the time from the first objective status assessment of CR or PR to the first date of progression or death as a result of any cause: CR was achieved if all tumor lesions disappeared; PR was achieved if there was \>=30% decrease in sum of the longest diameter (LD) of target lesions (reference: baseline sum LDs) or complete disappearance of target lesions with persistence (but not worsening) of \>=1 nontarget lesions and no appearance of new lesions.
Outcome measures
| Measure |
Pemetrexed
n=1 Participants
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Duration of Response
|
9.5 months
Interval 4.0 to
|
SECONDARY outcome
Timeframe: Baseline to 10.4 monthsPopulation: Full analysis population: all participants who were treated with at least one dose of the study regimen.
PFS was from date of study enrollment to first date of objectively determined progressive disease (PD) or death from any cause. For participants who did not die as of data cut-off date and who did not have objective PD, PFS was censored at date of last objective progression-free disease assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from study drug) before objectively determined disease progression or death, PFS was censored at date of last objective progression-free disease assessment, before post-discontinuation chemotherapy.
Outcome measures
| Measure |
Pemetrexed
n=32 Participants
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Progression-Free Survival (PFS)
|
1.4 months
Interval 1.4 to 1.7
|
SECONDARY outcome
Timeframe: Baseline to 27.6 monthsPopulation: Full analysis population: all participants who were treated with at least one dose of the study regimen.
OS was the duration from enrollment to death. For participants who lived, OS was censored at the last contact.
Outcome measures
| Measure |
Pemetrexed
n=32 Participants
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Overall Survival (OS) Time
|
5.5 months
Interval 2.3 to 10.5
|
Adverse Events
Pemetrexed
Serious adverse events
| Measure |
Pemetrexed
n=32 participants at risk
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Blood and lymphatic system disorders
Febrile bone marrow aplasia
|
3.1%
1/32 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.1%
1/32 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.1%
1/32 • Number of events 1
|
|
Cardiac disorders
Pericardial effusion
|
6.2%
2/32 • Number of events 2
|
|
General disorders
General physical health deterioration
|
3.1%
1/32 • Number of events 1
|
|
General disorders
Pyrexia
|
3.1%
1/32 • Number of events 1
|
|
General disorders
Sudden death
|
3.1%
1/32 • Number of events 1
|
|
Infections and infestations
Catheter related infection
|
3.1%
1/32 • Number of events 1
|
|
Infections and infestations
Sepsis
|
3.1%
1/32 • Number of events 1
|
|
Infections and infestations
Staphylococcal infection
|
3.1%
1/32 • Number of events 1
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
3.1%
1/32 • Number of events 1
|
|
Nervous system disorders
Nerve compression
|
3.1%
1/32 • Number of events 1
|
|
Renal and urinary disorders
Haematuria
|
3.1%
1/32 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
3.1%
1/32 • Number of events 1
|
|
Renal and urinary disorders
Ureteric obstruction
|
3.1%
1/32 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
3.1%
1/32 • Number of events 1
|
|
Reproductive system and breast disorders
Pelvic pain
|
3.1%
1/32 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.1%
1/32 • Number of events 1
|
|
Surgical and medical procedures
Vertebroplasty
|
3.1%
1/32 • Number of events 1
|
Other adverse events
| Measure |
Pemetrexed
n=32 participants at risk
Participants received pemetrexed 500 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion of 10 minutes on Day 1 of each 21-day cycle
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
18.8%
6/32 • Number of events 7
|
|
Blood and lymphatic system disorders
Leukopenia
|
9.4%
3/32 • Number of events 5
|
|
Blood and lymphatic system disorders
Neutropenia
|
9.4%
3/32 • Number of events 6
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.2%
2/32 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
15.6%
5/32 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
2/32 • Number of events 9
|
|
Gastrointestinal disorders
Nausea
|
12.5%
4/32 • Number of events 14
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
2/32 • Number of events 2
|
|
General disorders
Asthenia
|
25.0%
8/32 • Number of events 14
|
|
General disorders
Fatigue
|
12.5%
4/32 • Number of events 4
|
|
General disorders
Oedema peripheral
|
12.5%
4/32 • Number of events 4
|
|
General disorders
Pain
|
6.2%
2/32 • Number of events 2
|
|
Infections and infestations
Nasopharyngitis
|
6.2%
2/32 • Number of events 2
|
|
Investigations
Alanine aminotransferase increased
|
21.9%
7/32 • Number of events 8
|
|
Investigations
Aspartate aminotransferase increased
|
12.5%
4/32 • Number of events 4
|
|
Investigations
Blood alkaline phosphatase increased
|
6.2%
2/32 • Number of events 2
|
|
Metabolism and nutrition disorders
Anorexia
|
6.2%
2/32 • Number of events 5
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
9.4%
3/32 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
6.2%
2/32 • Number of events 10
|
|
Nervous system disorders
Headache
|
6.2%
2/32 • Number of events 6
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
6.2%
2/32 • Number of events 4
|
|
Psychiatric disorders
Depression
|
6.2%
2/32 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
6.2%
2/32 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
4/32 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.2%
2/32 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.2%
2/32 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Erythema
|
12.5%
4/32 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.4%
3/32 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.4%
3/32 • Number of events 4
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60