Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas
Condition: Sarcoma
MeSH terms: Sarcoma
Intervention: Irinotecan&Temsirolimus:Arm1, Level 1; Irinotecan&Temsirolimus:Arm 1, Level 2; Irinotecan&Temsirolimus:Arm 2, Level 1
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.; 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.; 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 MeSH terms: Sirolimus; Irinotecan; Temsirolimus; MTOR Inhibitors; Complement Factor H
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 10 Years
Healthy volunteers: No
Keywords: INST 0909; Irinotecan; Temsirolimus; refractory sarcomas; 3066K1; 3066K1-1208; 20091334

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.
    

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.