Trial Outcomes & Findings for Temsirolimus/AZD 6244 for Treatment-naive With BRAF Mutant Unresectable Stage IV (NCT NCT01166126)
NCT ID: NCT01166126
Last Updated: 2014-05-15
Results Overview
Anti-tumor response (CR+PR) was defined by Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
4 participants
Primary outcome timeframe
1 year
Results posted on
2014-05-15
Participant Flow
Up to 35 subjects with a histologic diagnosis of unresectable Stage IV melanoma were to be enrolled into this study over 24 months.
11 of 15 patients consented were not eligible to receive the study drug after screening.
Participant milestones
| Measure |
Treatment (Temsirolimus and Selumetinib)
Treatment Phase: This period begins with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.
The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.
|
|---|---|
|
Overall Study
STARTED
|
4
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Temsirolimus/AZD 6244 for Treatment-naive With BRAF Mutant Unresectable Stage IV
Baseline characteristics by cohort
| Measure |
Treatment (Temsirolimus and Selumetinib)
n=4 Participants
Treatment Phase: This period begins with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.
The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=39 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=39 Participants
|
|
Age, Continuous
|
52.5 years
n=39 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=39 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=39 Participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: All participants
Anti-tumor response (CR+PR) was defined by Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Outcome measures
| Measure |
Treatment (Temsirolimus and Selumetinib)
n=4 Participants
Treatment Phase: This period began with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.
The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.
|
|---|---|
|
Number of Participants With Complete Response (CR) and Partial Response (PR)
Partial Response
|
0 participants
|
|
Number of Participants With Complete Response (CR) and Partial Response (PR)
Complete Response
|
0 participants
|
PRIMARY outcome
Timeframe: 1 year post last treatmentThe one-year overall survival of the combination of temsirolimus and AZD6244 Hydrogen Sulfate.
Outcome measures
| Measure |
Treatment (Temsirolimus and Selumetinib)
n=4 Participants
Treatment Phase: This period began with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.
The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.
|
|---|---|
|
Number of Participants With Overall Survival (OS) at One Year
|
0 participants
|
SECONDARY outcome
Timeframe: 6 months from day 1 of treatmentPatients will be evaluated by physical examination and imaging assessments (brain MRI and CT scans of the chest, abdomen and pelvis). Disease progression will be defined by RECIST criteria on physical exam or diagnostic imaging assessments that are attributed to metastatic melanoma. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Outcome measures
| Measure |
Treatment (Temsirolimus and Selumetinib)
n=4 Participants
Treatment Phase: This period began with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.
The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.
|
|---|---|
|
Number of Participants With Progression Free Survival (PFS) at 6 Months.
|
1 participants
|
SECONDARY outcome
Timeframe: 1 yearToxicities assessed using NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0.
Outcome measures
| Measure |
Treatment (Temsirolimus and Selumetinib)
n=4 Participants
Treatment Phase: This period began with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.
The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.
|
|---|---|
|
Number of Participants With Related Serious Adverse Events (SAEs)
|
0 participants
|
Adverse Events
Treatment (Temsirolimus and Selumetinib)
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment (Temsirolimus and Selumetinib)
n=4 participants at risk
Treatment Phase: This period begins with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.
The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.
|
|---|---|
|
Ear and labyrinth disorders
Vertigo
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
General disorders
Fever
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benigh, malignant and unspecified (incl cysts and polyps) - other
|
25.0%
1/4 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Treatment (Temsirolimus and Selumetinib)
n=4 participants at risk
Treatment Phase: This period begins with the first intravenous (through the vein) infusion of TEMSIROLIMUS and the first AZD6244 administration by mouth (visit 2, Week 1) and will continue until Week 8 (Visit 4).
Investigators planned for as many as 38 patients to receive the same dosage of TEMSIROLIMUS injected in the veins once a week for 8 weeks, and the AZD6244 would be given as capsules by mouth twice a day for 8 weeks. That is one cycle. The TEMSIROLIMUS and AZD6244 would be given to participants as an outpatient, unless admission to the hospital was needed for treatment of related side effects or underlying disease. The subsequent cycles of TEMSIROLIMUS and AZD6244 would be given every 8 weeks. The TEMSIROLIMUS would be injected in a vein over 30 minutes.
The continuation phase would begin with visits at weeks 12 in patients who received at least two cycles of treatments.
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
100.0%
4/4 • Number of events 4 • 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
100.0%
4/4 • Number of events 20 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
75.0%
3/4 • Number of events 8 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
2/4 • Number of events 6 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Ascites
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal disorders - other
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • Number of events 2 • 1 year
|
|
General disorders
Fatigue
|
100.0%
4/4 • Number of events 8 • 1 year
|
|
General disorders
Fever
|
75.0%
3/4 • Number of events 5 • 1 year
|
|
General disorders
Edima - limbs
|
50.0%
2/4 • Number of events 3 • 1 year
|
|
General disorders
Pain
|
50.0%
2/4 • Number of events 4 • 1 year
|
|
General disorders
Chills
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
General disorders
Edema - face
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
General disorders
General disorders and administration site conditions - other
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Nervous system disorders
Dizziness
|
50.0%
2/4 • Number of events 2 • 1 year
|
|
Nervous system disorders
Dysgeusia
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Nervous system disorders
Headache
|
25.0%
1/4 • Number of events 2 • 1 year
|
|
Nervous system disorders
Paresthesia
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Nervous system disorders
Seizure
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
75.0%
3/4 • Number of events 3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
75.0%
3/4 • Number of events 9 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
50.0%
2/4 • Number of events 4 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
50.0%
2/4 • Number of events 9 • 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
1/4 • Number of events 3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Investigations
Lipase increased
|
50.0%
2/4 • Number of events 2 • 1 year
|
|
Investigations
Alkaline phosphatase increased
|
25.0%
1/4 • Number of events 2 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Investigations
Cholesterol high
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Investigations
Neutrophil count decreased
|
25.0%
1/4 • Number of events 14 • 1 year
|
|
Investigations
Serum amylase increased
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
50.0%
2/4 • Number of events 5 • 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
25.0%
1/4 • Number of events 2 • 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Psychiatric disorders
Anxiety
|
50.0%
2/4 • Number of events 2 • 1 year
|
|
Psychiatric disorders
Insomnia
|
50.0%
2/4 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
75.0%
3/4 • Number of events 3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
50.0%
2/4 • Number of events 5 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
25.0%
1/4 • Number of events 2 • 1 year
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - other
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Ear and labyrinth disorders
Tinnitus
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Ear and labyrinth disorders
Vertigo
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Hepatobiliary disorders
Hepatic pain
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Hepatobiliary disorders
Hepatobiliary disorders - other
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Infections and infestations
Tooth infection
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
1/4 • Number of events 2 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
25.0%
1/4 • Number of events 1 • 1 year
|
|
Vascular disorders
Hypertension
|
25.0%
1/4 • Number of events 2 • 1 year
|
Additional Information
Ragini Kudchadkar, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-8581
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60