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

This study has been terminated.
(Original PI left institution and sponsor decided to end support.)
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier:
NCT00996346
First received: October 14, 2009
Last updated: August 2, 2015
Last verified: August 2015
  Purpose

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.


Condition Intervention Phase
Sarcoma
Drug: Irinotecan&Temsirolimus:Arm1, Level 1
Drug: Irinotecan&Temsirolimus:Arm 1, Level 2
Drug: Irinotecan&Temsirolimus:Arm 2, Level 1
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas

Resource links provided by NLM:


Further study details as provided by New Mexico Cancer Care Alliance:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Irinotecan [ Time Frame: Up to 1 month ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 1 month ] [ Designated as safety issue: Yes ]
    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


Enrollment: 17
Study Start Date: October 2009
Study Completion Date: November 2013
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: Irinotecan&Temsirolimus:Arm1, 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.
Other Names:
  • Irinotecan = Camptosar, Campto, or CPT-11
  • Temsirolimus = Toricel or CCI-779
Experimental: 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.

Drug: Irinotecan&Temsirolimus:Arm 1, Level 2
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.
Other Names:
  • Irinotecan = Camptosar, Campto, or CPT-11
  • Temsirolimus = Toricel or CCI-779
Experimental: 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.

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.
Other Names:
  • Irinotecan = Camptosar, Campto, or CPT-11
  • Temsirolimus = Toricel or CCI-779

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.

  Eligibility

Ages Eligible for Study:   10 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00996346

Locations
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
Sponsors and Collaborators
New Mexico Cancer Care Alliance
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Monte Shaheen, MD University of New Mexico Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier: NCT00996346     History of Changes
Other Study ID Numbers: INST 0909  3066K1  3066K1-1208  20091334  NCI-2011-01940 
Study First Received: October 14, 2009
Results First Received: June 6, 2015
Last Updated: August 2, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by New Mexico Cancer Care Alliance:
INST 0909
Irinotecan
Temsirolimus
refractory sarcomas
3066K1
3066K1-1208
20091334

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Irinotecan
Camptothecin
Everolimus
Sirolimus
Complement Factor H
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on September 29, 2016