A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours

Inclusion Criteria

• •Eligibility Criteria - ALL Patients
• •Patients must have histologically or cytologically confirmed diagnosis of a rare tumour as follows:
• •1. Vascular sarcomas: Angiosarcoma, hemangiosarcoma, hemangiopericytoma, hemangioblastomas;
• •2. Clear cell carcinomas of the ovary, endometrium;
• •3. Medullary thyroid carcinoma;
• •4. Neuroendocrine tumours: paragangliomas and pheochromocytomas only;
• •5. Adrenocorticocarcinoma;
• •6. Thymic carcinoma;
• •7. Fibrolamellar hepatocellular carcinoma;
• •8. Exploratory genetic cohort for sunitinib: Rare tumours with somatic or germline mutations in sunitinib targets such as VEGFR, PDGFR, KIT, RET;
• •9. Exploratory genetic cohort for temsirolimus: Rare tumours arising from known or suspected germline mutations in mTOR pathway such as PTEN, TS1/2, LKB1, NF1/2 or somatic mutations in the mTOR pathway such as mutation or amplification of P13K or AKT;
• •10. Unspecified cohort for exploratory evaluation. The unspecified histologies must also be rare tumours for which there are no traditional phase II clinical trials and for which there are clinical activity or laboratory data to support the likely sensitivity to the agents.
• •11. Ewing's Sarcoma Family of Tumours (ESFT) - relapsed or refractory.
• •* Patients must have unresectable, locally advanced or metastatic disease for which there are no known life prolonging standard therapies.
• •* Patients must have tumour tissue from their primary tumour available
• •* Presence of clinically and/or radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows:
• •Chest x-ray ≥ 20 mm Ct scan (with slice thickness of ≤ 5 mm) - ≥ 10 mm --\> Longest diameter Physical exam (using calipers) - ≥ 10 mm Lymph nodes by ct scan - ≥ 15 mm --\> Measured in short axis
• •All radiology studies must be performed within 21 days prior to registration (within 28 days if negative).
• •* Age ≥ 16 years for cohorts #1-10; age ≥ 5 years for cohort #11 (ESFT) only.
• •* Patients must have a life expectancy of at least 12 weeks.
• •* ECOG performance status 0, 1 or 2.
• •* Previous Therapy Chemotherapy: Patients may have received prior chemotherapy (no limit on number of prior regimens), however no prior treatment with relevant mTOR or VEGFR, KIT, RET, PDGFR inhibitors is permitted (i.e. to be eligible for sunitinib: no prior treatment with VEGFR, KIT, RET or PDGFR inhibitors permitted; to be eligible for temsirolimus: no prior treatment with mTOR inhibitors permitted). A minimum of 28 days (4 weeks) must have elapsed since the last dose of chemotherapy prior to registration. Patients must have recovered from any treatment related toxicities prior to registration.
• •Radiation: Patients may have had prior radiation therapy. A minimum of 28 days (4 weeks) since the last dose of radiation must have elapsed prior to registration (exceptions may be made for low dose, palliative radiotherapy. Patients must have recovered from any acute toxic effects from radiation prior to registration.
• •Previous surgery: is permitted provided that wound healing has occurred and at least 28 days have elapsed prior to registration if surgery was major.
• •Laboratory Requirements:
• •(must be done within 7 days prior to registration) Hematology Absolute granulocytes: ≥ 1.5 x 10\^9/L Platelets: ≥ 100 x 10\^9/L
• •Chemistry:
• •ALL Patients Bilirubin ≤ 1.5 x UNL (upper normal limit) AST and ALT ≤ 2.5 x UNL Serum Creatinine ≤UNL or: Creatinine clearance ≥ 60ml/min
• •Chemistry:
• •TEMSIROLIMUS Arm Only Fasting cholesterol ≤ 9.0 mmol/L Fasting triglycerides ≤ 4.56 mmol/L
• •\* Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft Formula: Females: GFR = 1.04 x (140-age) x weight in kg serum creatinine in μmol/L Males: GFR = 1.23 x (140-age) x weight in kg serum creatinine in μmol/L
• •* Patient or guardian consent must be obtained on all patients according to local Institutional and/or University Human Experimentation Committee requirements. Children \> 8 years old whose parent or guardian has signed consent on their behalf may also sign assent if desired. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, a standard consent form for the trial will not be provided but a sample form is provided. A copy of the initial full board REB approval and approved consent form must be sent to the central office. The patient or their parent/legal guardian must sign the consent form prior to registration. Please note that the consent form for this study must contain a statement which gives permission for the NCIC CTG and monitoring agencies to review patient records.
• •* Patients must be accessible for treatment, response assessment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. (Call the NCIC CTG office at 613-533-6430 if questions arise regarding the interpretation of this criterion.) Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
• •In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient registration.
• •Ineligibility Criteria - ALL Patients