Trial Outcomes & Findings for Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas (NCT NCT00996346)
NCT ID: NCT00996346
Last Updated: 2015-09-01
Results Overview
The MTD is the dose preceding that at which at least 2 out of 3 patients in the treatment group experience a dose limiting toxicity (DLT). DLT is defined as grade 3 neutropenia on retreatment day, a grade 4 febrile neutropenia, a drug-related grade 3 or 4 non-hematologic toxicity (except fatigue, nausea, vomiting or grade 3 hypersensitivity reaction) or a grade 2 or greater motor or sensory neuropathy
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
17 participants
Primary outcome timeframe
Up to 1 month
Results posted on
2015-09-01
Participant Flow
Subjects were recruited between October, 2009, and May, 2011
Participant milestones
| Measure |
Irinotecan&Temsirolimus:Arm 1, Level 1
Arm 1, Level 1: Irinotecan intravenously at 80 mg/m2 + Temsirolimus intravenously at 15 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
One cycle is four weeks.
|
Irinotecan&Temsirolimus:Arm 1, Level 2
Arm 1, Level 2: Irinotecan intravenously at 80 mg/m2 + Temsirolimus intravenously at 20 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
One cycle is four weeks.
|
Irinotecan&Temsirolimus:Arm 2, Level 1
Arm 1, Level 2: Irinotecan intravenously at 50 mg/m2 + Temsirolimus intravenously at 25 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
8
|
3
|
|
Overall Study
COMPLETED
|
6
|
8
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas
Baseline characteristics by cohort
| Measure |
Irinotecan&Temsirolimus:Arm 1, Level 1
n=6 Participants
Arm 1, Level 1: Irinotecan intravenously at 80 mg/m2 + Temsirolimus intravenously at 15 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
One cycle is four weeks.
|
Irinotecan&Temsirolimus:Arm 1, Level 2
n=8 Participants
Arm 1, Level 2: Irinotecan intravenously at 80 mg/m2 + Temsirolimus intravenously at 20 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
One cycle is four weeks.
|
Irinotecan&Temsirolimus:Arm 2, Level 1
n=3 Participants
Arm 1, Level 2: Irinotecan intravenously at 50 mg/m2 + Temsirolimus intravenously at 25 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
60.5 years
n=99 Participants
|
47.5 years
n=107 Participants
|
56 years
n=206 Participants
|
56 years
n=7 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=99 Participants
|
8 participants
n=107 Participants
|
3 participants
n=206 Participants
|
17 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Up to 1 monthThe MTD is the dose preceding that at which at least 2 out of 3 patients in the treatment group experience a dose limiting toxicity (DLT). DLT is defined as grade 3 neutropenia on retreatment day, a grade 4 febrile neutropenia, a drug-related grade 3 or 4 non-hematologic toxicity (except fatigue, nausea, vomiting or grade 3 hypersensitivity reaction) or a grade 2 or greater motor or sensory neuropathy
Outcome measures
| Measure |
Irinotecan&Temsirolimus:All Arms
n=17 Participants
Data from the dose escalation in all three arms is used to calculate the maximum tolerated dose (MTD).
In all three arms, Irinotecan and temsirolimus will be repeated weekly x 3 doses followed by one week of rest. One course will be four weeks.
The treatment consists of:
Irinotecan at 50 - 80 mg/m2 weekly, for three weeks + Temsirolimus at 15 - 25 mg weekly, for three weeks.
The specific doses of Irinotecan are 50, 65, or 80 mg/m2 The specific doses of Temsirolimus are 15, 20, or 25 mg
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Irinotecan
|
80 milligrams/meter squared
|
PRIMARY outcome
Timeframe: Up to 1 monthThe MTD is the dose preceding that at which at least 2 out of 3 patients in the treatment group experience a dose limiting toxicity (DLT). DLT is defined as grade 3 neutropenia on retreatment day, a grade 4 febrile neutropenia, a drug-related grade 3 or 4 non-hematologic toxicity (except fatigue, nausea, vomiting or grade 3 hypersensitivity reaction) or a grade 2 or greater motor or sensory neuropathy
Outcome measures
| Measure |
Irinotecan&Temsirolimus:All Arms
n=17 Participants
Data from the dose escalation in all three arms is used to calculate the maximum tolerated dose (MTD).
In all three arms, Irinotecan and temsirolimus will be repeated weekly x 3 doses followed by one week of rest. One course will be four weeks.
The treatment consists of:
Irinotecan at 50 - 80 mg/m2 weekly, for three weeks + Temsirolimus at 15 - 25 mg weekly, for three weeks.
The specific doses of Irinotecan are 50, 65, or 80 mg/m2 The specific doses of Temsirolimus are 15, 20, or 25 mg
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Temsirolimus
|
20 milligrams
|
Adverse Events
Irinotecan&Temsirolimus:Arm 1, Level 1
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Irinotecan&Temsirolimus:Arm 1, Level 2
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Irinotecan&Temsirolimus:Arm 2, Level 1
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Irinotecan&Temsirolimus:Arm 1, Level 1
n=6 participants at risk
Arm 1, Level 1: Irinotecan intravenously at 80 mg/m2 + Temsirolimus intravenously at 15 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
One cycle is four weeks.
|
Irinotecan&Temsirolimus:Arm 1, Level 2
n=8 participants at risk
Arm 1, Level 2: Irinotecan intravenously at 80 mg/m2 + Temsirolimus intravenously at 20 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
One cycle is four weeks.
|
Irinotecan&Temsirolimus:Arm 2, Level 1
n=3 participants at risk
Arm 1, Level 2: Irinotecan intravenously at 50 mg/m2 + Temsirolimus intravenously at 25 mg on a weekly basis for 3 consecutive doses followed by one week of rest.
|
|---|---|---|---|
|
General disorders
Allergic reaction
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
General disorders
Rhinitis (Runny nose)
|
50.0%
3/6 • Number of events 3
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Hemoglobin levels decreased
|
16.7%
1/6 • Number of events 1
|
37.5%
3/8 • Number of events 4
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Hemolysis (red blood cell destruction)
|
0.00%
0/6
|
50.0%
4/8 • Number of events 6
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Leukocytes decreased
|
16.7%
1/6 • Number of events 1
|
75.0%
6/8 • Number of events 16
|
66.7%
2/3 • Number of events 2
|
|
Blood and lymphatic system disorders
Lymphocytes decreased
|
0.00%
0/6
|
100.0%
8/8 • Number of events 22
|
66.7%
2/3 • Number of events 2
|
|
Blood and lymphatic system disorders
Neutrophils decreased
|
33.3%
2/6 • Number of events 3
|
25.0%
2/8 • Number of events 10
|
66.7%
2/3 • Number of events 2
|
|
Blood and lymphatic system disorders
Platelets decreased
|
50.0%
3/6 • Number of events 4
|
25.0%
2/8 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
|
Cardiac disorders
Hypotension
|
0.00%
0/6
|
25.0%
2/8 • Number of events 3
|
0.00%
0/3
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/6
|
25.0%
2/8 • Number of events 2
|
0.00%
0/3
|
|
General disorders
Fatigue
|
66.7%
4/6 • Number of events 5
|
37.5%
3/8 • Number of events 4
|
66.7%
2/3 • Number of events 2
|
|
General disorders
Fever
|
33.3%
2/6 • Number of events 2
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
General disorders
Weight loss
|
0.00%
0/6
|
0.00%
0/8
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Dermatology/Skin - Other
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/3
|
|
General disorders
Rigors/chills
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Alopecia (Hair loss)
|
0.00%
0/6
|
12.5%
1/8 • Number of events 2
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Pruritus (Itching)
|
0.00%
0/6
|
25.0%
2/8 • Number of events 3
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/6
|
25.0%
2/8 • Number of events 2
|
66.7%
2/3 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal distention
|
0.00%
0/6
|
0.00%
0/8
|
66.7%
2/3 • Number of events 4
|
|
Gastrointestinal disorders
Anorexia (Loss of appetite)
|
33.3%
2/6 • Number of events 3
|
12.5%
1/8 • Number of events 1
|
66.7%
2/3 • Number of events 3
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/6
|
0.00%
0/8
|
66.7%
2/3 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6
|
0.00%
0/8
|
66.7%
2/3 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis oral
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
25.0%
2/8 • Number of events 2
|
100.0%
3/3 • Number of events 5
|
|
Gastrointestinal disorders
Nausea
|
33.3%
2/6 • Number of events 3
|
50.0%
4/8 • Number of events 4
|
66.7%
2/3 • Number of events 4
|
|
General disorders
Hemorrhage nasal
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Myositis (Muscle inflammation)
|
0.00%
0/6
|
12.5%
1/8 • Number of events 2
|
0.00%
0/3
|
|
Infections and infestations
Throat Infection
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Edema: limbs
|
0.00%
0/6
|
12.5%
1/8 • Number of events 2
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Edema: head and neck
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/6
|
37.5%
3/8 • Number of events 5
|
0.00%
0/3
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Investigations
Creatinine increased
|
0.00%
0/6
|
37.5%
3/8 • Number of events 5
|
0.00%
0/3
|
|
Investigations
Hypercalcemia
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Investigations
Hyperglycemia
|
33.3%
2/6 • Number of events 4
|
75.0%
6/8 • Number of events 7
|
66.7%
2/3 • Number of events 2
|
|
Investigations
Hypoalbuminemia
|
0.00%
0/6
|
50.0%
4/8 • Number of events 6
|
33.3%
1/3 • Number of events 1
|
|
Investigations
Hypocalcemia
|
0.00%
0/6
|
0.00%
0/8
|
33.3%
1/3 • Number of events 1
|
|
Investigations
Hypokalemia
|
16.7%
1/6 • Number of events 1
|
12.5%
1/8 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Investigations
Hypomagnesemia
|
0.00%
0/6
|
37.5%
3/8 • Number of events 4
|
0.00%
0/3
|
|
Investigations
Hyponatremia
|
0.00%
0/6
|
50.0%
4/8 • Number of events 4
|
0.00%
0/3
|
|
Investigations
Hypophosphatemia
|
0.00%
0/6
|
12.5%
1/8 • Number of events 2
|
0.00%
0/3
|
|
Investigations
INR (Prothrombin time)
|
16.7%
1/6 • Number of events 3
|
12.5%
1/8 • Number of events 2
|
0.00%
0/3
|
|
Investigations
Laboratory test abnormal
|
0.00%
0/6
|
37.5%
3/8 • Number of events 4
|
0.00%
0/3
|
|
Investigations
Prothromboplastin time
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/6
|
0.00%
0/8
|
33.3%
1/3 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Extraocular muscle disorder
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Gait abnormal
|
0.00%
0/6
|
12.5%
1/8 • Number of events 2
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/6
|
0.00%
0/8
|
33.3%
1/3 • Number of events 1
|
|
Psychiatric disorders
Cognitive disturbance
|
0.00%
0/6
|
0.00%
0/8
|
33.3%
1/3 • Number of events 1
|
|
Psychiatric disorders
Depression
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Psychiatric disorders
Dizziness
|
0.00%
0/6
|
0.00%
0/8
|
66.7%
2/3 • Number of events 3
|
|
General disorders
Headache
|
16.7%
1/6 • Number of events 2
|
37.5%
3/8 • Number of events 3
|
33.3%
1/3 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Eye disorders
Vision blurred
|
16.7%
1/6 • Number of events 2
|
12.5%
1/8 • Number of events 1
|
33.3%
1/3 • Number of events 2
|
|
General disorders
Ear, nose and throat examination abnormal
|
16.7%
1/6 • Number of events 1
|
12.5%
1/8 • Number of events 2
|
0.00%
0/3
|
|
General disorders
Abdominal pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Back pain
|
33.3%
2/6 • Number of events 2
|
0.00%
0/8
|
0.00%
0/3
|
|
General disorders
Joint pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
0.00%
0/3
|
|
General disorders
Pain in extremity
|
16.7%
1/6 • Number of events 1
|
37.5%
3/8 • Number of events 9
|
0.00%
0/3
|
|
General disorders
Bone pain
|
0.00%
0/6
|
12.5%
1/8 • Number of events 3
|
0.00%
0/3
|
|
General disorders
Chest pain
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
General disorders
Chest wall pain
|
0.00%
0/6
|
0.00%
0/8
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Pharyngolaryngeal pain
|
0.00%
0/6
|
12.5%
1/8 • Number of events 1
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
16.7%
1/6 • Number of events 3
|
12.5%
1/8 • Number of events 4
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1
|
0.00%
0/8
|
33.3%
1/3 • Number of events 2
|
|
Vascular disorders
Thrombosis
|
16.7%
1/6 • Number of events 3
|
0.00%
0/8
|
0.00%
0/3
|
Additional Information
Monte Shaheen, MD / Study Principal Investigator
University of New Mexico Cancer Center
Phone: 505-925-0404
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place