Temsirolimus, Irinotecan Hydrochloride, and Temozolomide in Treating Younger Patients With Relapsed or Refractory Solid Tumors

Inclusion Criteria:

• Histologically confirmed solid tumor at original diagnosis or relapse except for the following, which do not require biopsies:

  • Intrinsic brain stem tumors
  • Optic pathway gliomas
  • Pineal tumors with elevations of serum, CSF alpha-fetoprotein, or beta-HCG
• Recurrent or refractory disease
• Measurable or evaluable disease
• Disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Patients with CNS tumors must have been relatively stable for ≥ 1 week
• Karnofsky performance status (PS) 50-100% (patients > 16 years of age) OR Lansky PS 50-100% (patients ≤ 16 years of age)
• ANC ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3 (transfusion independent)

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age and/or gender as follows:

  • ≤ 0.6 mg/dL (1 to < 2 years of age)
  • ≤ 0.8 mg/dL (2 to < 6 years of age)
  • ≤ 1.0 mg/dL (6 to < 10 years of age)
  • ≤ 1.2 mg/dL (10 to < 13 years of age)
  • ≤ 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
  • ≤ 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 110 U/L
• Serum albumin > 2 g/dL
• PT < 1.2 times ULN
• Serum triglycerides ≤ 300 mg/dL
• Serum cholesterol ≤ 300 mg/dL
• Random or fasting blood glucose normal
• Normal pulmonary function tests, including DLCO, if clinically indicated (e.g., dyspnea at rest, known requirement for supplemental oxygen)
• Patients with seizure disorder allowed provided it is well controlled with non-enzyme-inducing anticonvulsants
• Nervous system disorders resulting from prior therapy ≤ grade 2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
• No history of allergic reactions attributed to compounds of similar composition to irinotecan hydrochloride, temozolomide, or temsirolimus
• No evidence of graft-vs-host disease
• Fully recovered from all prior anticancer therapy
• More than 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosourea)
• At least 14 days since prior long-acting growth factor (e.g., Neulasta) OR 7 days for short-acting growth factor
• At least 7 days since prior biologic agent that is not a monoclonal antibody (e.g., platelet infusions)
• At least 6 weeks since prior immunotherapies (e.g., tumor vaccines)
• At least 3 half-lives since prior monoclonal antibody therapy

• At least 2 weeks since prior local palliative radiotherapy (small port)

  • At least 24 weeks since prior total-body irradiation, craniospinal radiotherapy (RT), or RT to ≥ 50% to the pelvis
  • At least 6 weeks since prior substantial bone marrow RT
• At least 12 weeks since prior stem cell transplantation or stem cell infusion without RT

• Prior irinotecan hydrochloride, temozolomide, and temsirolimus as single agents or a combination of 2 of the 3 drugs, including irinotecan hydrochloride and temozolomide, allowed

  • No prior combination of the 3 agents

• Concurrent corticosteroids allowed provided dose has been stable or decreasing for 7 days

  • Intermittent use of corticosteroids to manage infusional reactions is allowed

• More than 6 weeks since prior major surgery

  • Recent minor surgical procedures (e.g., vascular catheter placement, bone marrow evaluation, or laparoscopic surgery) allowed
• No other concurrent investigational drugs
• No other concurrent anticancer agents, including chemotherapy, RT, immunotherapy, or biologic therapy
• No concurrent enzyme-inducing anticonvulsants

• No concurrent CYP3A4 inducers or inhibitors including any of the following:

  • Erythromycin
  • Clarithromycin
  • Ketoconazole
  • Azithromycin
  • Itraconazole
  • Grapefruit juice
  • St. John wort
• No concurrent therapeutic anticoagulants, including aspirin or low molecular weight heparin
• No concurrent angiotensin-converting enzyme (ACE) inhibitors
• No concurrent cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post-bone marrow transplant or organ rejection post-transplant