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Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas

Primary Purpose

Sarcoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Irinotecan&Temsirolimus:Arm1, Level 1
Irinotecan&Temsirolimus:Arm 1, Level 2
Irinotecan&Temsirolimus:Arm 2, Level 1
Sponsored by
New Mexico Cancer Care Alliance
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring INST 0909, Irinotecan, Temsirolimus, refractory sarcomas, 3066K1, 3066K1-1208, 20091334

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • All patients, 10 years of age or older with biopsy proven advanced soft tissue sarcoma, who have failed at least one prior treatment for metastatic disease are eligible if there is measurable or evaluable disease per Response Evaluation Criteria In Solid Tumors (RECIST).
  • Patients must have a life expectancy of at least 12 weeks.
  • Prior surgery or radiotherapy for primary tumor is acceptable but must be completed at least 4 weeks from study entry, and patient should have completely recovered from such procedures.
  • Patients must have a Zubrod performance status of 0-2.
  • Patients (or their legal guardian) must sign an informed consent.
  • Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of ≥ 1500 cells/mm3, hemoglobin > 8 g/dl, platelet count ≥ 100 000/mm3 and absence of a regular red blood cell transfusion requirement.
  • Patients should have a normal hepatic function with a total bilirubin < the upper limit of normal and Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) < 2 times the upper limit of normal, and adequate renal function as defined by a serum creatinine ≤ 1.5 upper limit of normal.
  • Fasting total cholesterol level < 350 mg/dL and triglyceride level < 400 mg/dL is required.
  • Women of childbearing potential must have a negative pregnancy test.
  • Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and at least for 3 months.

Patients with brain metastases are eligible if they have been appropriately treated,are asymptomatic and no longer require corticosteroids.

Exclusion Criteria:

  • Pregnant women or nursing mothers are not eligible.
  • Patients must not receive any other concurrent chemotherapy or radiation during this trial.
  • Patients with severe medical illnesses such as uncontrolled diabetes, active infections, or uncontrolled psychiatric illnesses are not eligible.
  • Patients with known hypersensitivity to temsirolimus or sirolimus, receiving concomitant antitumor therapy, or anticonvulsant therapy, or cardiac antiarrhythmic drugs are not eligible.

Sites / Locations

  • University of New Mexico Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Irinotecan&Temsirolimus:Arm 1, Level 1

Irinotecan&Temsirolimus:Arm 1, Level 2

Irinotecan&Temsirolimus:Arm 2, Level 1

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Full Information

First Posted
October 14, 2009
Last Updated
August 2, 2015
Sponsor
New Mexico Cancer Care Alliance
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00996346
Brief Title
Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas
Official Title
Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Terminated
Why Stopped
Original PI left institution and sponsor decided to end support.
Study Start Date
October 2009 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New Mexico Cancer Care Alliance
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma
Keywords
INST 0909, Irinotecan, Temsirolimus, refractory sarcomas, 3066K1, 3066K1-1208, 20091334

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Irinotecan&Temsirolimus:Arm 1, Level 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Irinotecan&Temsirolimus:Arm 1, Level 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Irinotecan&Temsirolimus:Arm 2, Level 1
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Irinotecan&Temsirolimus:Arm1, Level 1
Other Intervention Name(s)
Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Irinotecan&Temsirolimus:Arm 1, Level 2
Other Intervention Name(s)
Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Irinotecan&Temsirolimus:Arm 2, Level 1
Other Intervention Name(s)
Irinotecan = Camptosar, Campto, or CPT-11, Temsirolimus = Toricel or CCI-779
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of Irinotecan
Description
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
Title
Maximum Tolerated Dose (MTD) of Temsirolimus
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients, 10 years of age or older with biopsy proven advanced soft tissue sarcoma, who have failed at least one prior treatment for metastatic disease are eligible if there is measurable or evaluable disease per Response Evaluation Criteria In Solid Tumors (RECIST). Patients must have a life expectancy of at least 12 weeks. Prior surgery or radiotherapy for primary tumor is acceptable but must be completed at least 4 weeks from study entry, and patient should have completely recovered from such procedures. Patients must have a Zubrod performance status of 0-2. Patients (or their legal guardian) must sign an informed consent. Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of ≥ 1500 cells/mm3, hemoglobin > 8 g/dl, platelet count ≥ 100 000/mm3 and absence of a regular red blood cell transfusion requirement. Patients should have a normal hepatic function with a total bilirubin < the upper limit of normal and Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) < 2 times the upper limit of normal, and adequate renal function as defined by a serum creatinine ≤ 1.5 upper limit of normal. Fasting total cholesterol level < 350 mg/dL and triglyceride level < 400 mg/dL is required. Women of childbearing potential must have a negative pregnancy test. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and at least for 3 months. Patients with brain metastases are eligible if they have been appropriately treated,are asymptomatic and no longer require corticosteroids. Exclusion Criteria: Pregnant women or nursing mothers are not eligible. Patients must not receive any other concurrent chemotherapy or radiation during this trial. Patients with severe medical illnesses such as uncontrolled diabetes, active infections, or uncontrolled psychiatric illnesses are not eligible. Patients with known hypersensitivity to temsirolimus or sirolimus, receiving concomitant antitumor therapy, or anticonvulsant therapy, or cardiac antiarrhythmic drugs are not eligible.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Monte Shaheen, MD
Organizational Affiliation
University of New Mexico Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24216984
Citation
Verschraegen CF, Movva S, Ji Y, Schmit B, Quinn RH, Liem B, Bocklage T, Shaheen M. A phase I study of the combination of temsirolimus with irinotecan for metastatic sarcoma. Cancers (Basel). 2013 Apr 11;5(2):418-29. doi: 10.3390/cancers5020418.
Results Reference
result
Links:
URL
http://www.nmcca.org
Description
New Mexico Cancer Care Alliance
URL
http://cancer.unm.edu
Description
University of New Mexico Cancer Center

Learn more about this trial

Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas

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