A Phase 1 interventional study of Irinotecan&Temsirolimus:Arm1, Level 1 and Irinotecan&Temsirolimus:Arm 1, Level 2 in Sarcoma, sponsored by New Mexico Cancer Research Alliance. Terminated at 1 site in United States. Open to participants aged 10 Years and older. Per ClinicalTrials.gov, last updated 2015-09-01.
Sponsored by New Mexico Cancer Research Alliance · Phase 1, Interventional, and Treatment
Refractory soft tissue sarcoma remains a difficult malignancy to treat. The mammalian target of rapamycin (mTOR) is an enzyme that plays an important role in cancer cell survival. mTOR inhibitors, like temsirolimus, have shown activity in sarcoma. Irinotecan is a chemotherapy drug that has also been used to treat sarcoma. However, it is unknown whether combining these two drugs would result in improved efficacy with acceptable toxicity.
Therefore, the goal of this phase I study is to determine the maximum tolerated dose (MTD) and toxicity profile of combination temsirolimus and irinotecan both administered intravenously on a weekly basis to refractory soft tissue sarcoma patients.
Mammalian target of rapamycin (mTOR) inhibitors are anti-neoplastic agents with a wide potential range of clinical applications. The topoisomerase I inhibitor irinotecan is a potent DNA damaging drug. mTOR appears to enhance cancer cell survival following DNA damage, so it's reasonable to expect that mTOR inhibition combined with irinotecan may result in synergistic activity.
This is a single arm, non-randomized phase I trial of temsirolimus (an mTOR inhibitor) and irinotecan (a topoisomerase I inhibitor) in refractory soft tissue sarcoma patients. Successive groups of three patients will be entered at escalating dose levels. Irinotecan and temsirolimus will be administered weekly for three weeks followed by one week of rest. One course will therefore be four weeks. No intra-patient dose escalation will be allowed. Each patient will be treated until disease progression or intolerable side effects develop. Dose limiting toxicities will be assessed and the maximum tolerated dose will be reported.
Note that this trial was originally designed as a phase I/II study, but only the phase I portion was completed and will be reported.
1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.
This study's enrollment of 17 is below the median of 40 across 1,283 interventional studies indexed under Sarcoma.
Browse Sarcoma studies →New Mexico Cancer Research Alliance is the lead sponsor of 70 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients with brain metastases are eligible if they have been appropriately treated,are asymptomatic and no longer require corticosteroids.
Exclusion Criteria:
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.
Drug: Irinotecan&Temsirolimus:Arm1, Level 1
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.
Drug: Irinotecan&Temsirolimus:Arm 1, Level 2
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. One cycle is four weeks.
Drug: Irinotecan&Temsirolimus:Arm 2, Level 1
Irinotecan is given first over 60 minutes followed by temsirolimus over 30 minutes. No intrapatient dose escalations are allowed. Treatment continues until disease progression or intolerable side effects develop.
Also known as: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Irinotecan is given first over 60 minutes followed by temsirolimus over 30 minutes. No intrapatient dose escalations are allowed. Treatment continues until disease progression or intolerable side effects develop.
Also known as: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Irinotecan is given first over 60 minutes followed by temsirolimus over 30 minutes. No intrapatient dose escalations are allowed. Treatment continues until disease progression or intolerable side effects develop.
Also known as: Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Maximum Tolerated Dose (MTD) of Irinotecan
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
Time frame: Up to 1 month
Maximum Tolerated Dose (MTD) of Temsirolimus
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
Time frame: Up to 1 month
Subjects were recruited between October, 2009, and May, 2011
| Milestone | Irinotecan&Temsirolimus:Arm 1, Level 1 | Irinotecan&Temsirolimus:Arm 1, Level 2 | Irinotecan&Temsirolimus:Arm 2, Level 1 |
|---|---|---|---|
| Started | 6 | 8 | 3 |
| Completed | 6 | 8 | 3 |
| Not completed | 0 | 0 | 0 |
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
| milligrams/meter squared | Irinotecan&Temsirolimus:All Arms |
|---|---|
| Maximum Tolerated Dose (MTD) of Irinotecan | 80 |
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
| milligrams | Irinotecan&Temsirolimus:All Arms |
|---|---|
| Maximum Tolerated Dose (MTD) of Temsirolimus | 20 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Irinotecan&Temsirolimus:Arm 1, Level 1 | — | 0/6 (0%) | 6/6 (100%) |
| Irinotecan&Temsirolimus:Arm 1, Level 2 | — | 0/8 (0%) | 8/8 (100%) |
| Irinotecan&Temsirolimus:Arm 2, Level 1 | — | 0/3 (0%) | 3/3 (100%) |
| Event | Irinotecan&Temsirolimus:Arm 1, Level 1 | Irinotecan&Temsirolimus:Arm 1, Level 2 | Irinotecan&Temsirolimus:Arm 2, Level 1 |
|---|---|---|---|
| Lymphocytes decreasedBlood and lymphatic system disorders | 0/6 | 8/8 | 2/3 |
| VomitingGastrointestinal disorders | 0/6 | 2/8 | 3/3 |
| Leukocytes decreasedBlood and lymphatic system disorders | 1/6 | 6/8 | 2/3 |
| HyperglycemiaInvestigations | 2/6 | 6/8 | 2/3 |
| Neutrophils decreasedBlood and lymphatic system disorders | 2/6 | 2/8 | 2/3 |
| FatigueGeneral disorders | 4/6 | 3/8 | 2/3 |
| RashSkin and subcutaneous tissue disorders | 0/6 | 2/8 | 2/3 |
| Abdominal distentionGastrointestinal disorders | 0/6 | 0/8 | 2/3 |
| Anorexia (Loss of appetite)Gastrointestinal disorders | 2/6 | 1/8 | 2/3 |
| ConstipationGastrointestinal disorders | 0/6 | 0/8 | 2/3 |
| Age, Continuous(years) | Irinotecan&Temsirolimus:Arm 1, Level 1 | Irinotecan&Temsirolimus:Arm 1, Level 2 | Irinotecan&Temsirolimus:Arm 2, Level 1 | Total |
|---|---|---|---|---|
| Median | 60.5 (48 to 69) | 47.5 (25 to 72) | 56 (56 to 64) | 56 (25 to 72) |
| Sex: Female, Male(Participants) | Irinotecan&Temsirolimus:Arm 1, Level 1 | Irinotecan&Temsirolimus:Arm 1, Level 2 | Irinotecan&Temsirolimus:Arm 2, Level 1 | Total |
|---|---|---|---|---|
| Female | 3 | 4 | 1 | 8 |
| Male | 3 | 4 | 2 | 9 |
| Region of Enrollment(participants) | Irinotecan&Temsirolimus:Arm 1, Level 1 | Irinotecan&Temsirolimus:Arm 1, Level 2 | Irinotecan&Temsirolimus:Arm 2, Level 1 | Total |
|---|---|---|---|---|
| United States | 6 | 8 | 3 | 17 |
This study is terminated, as verified in Aug 2015. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
New Mexico Cancer Research Alliance