Patients with metastatic RCC MedDRA version: 9.1 Level: LLT Classification code 10050018 Term: Renal cancer metastatic
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TEMSIROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Sponsors
CONSORZIO ONCOTECH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Study subjects must have a histologically/cytologically confirmed diagnosis of metastatic RCC (regardless of nephrectomy status) with well-documented progressive disease (PD) after any of the following: cytokines (± chemotherapy), sunitinib, sorafenib, or bevacizumab (± IFN). 2. No more than one prior systemic treatment for advanced disease is allowed. 3. At least 2 weeks since prior systemic treatment, palliative radiation therapy, and/or surgery must have elapsed and resolution of all toxic effects of prior therapy to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE, version 3.0) Grade 1 must be observed prior to inclusion. 4. At least 1 measurable lesion that can be accurately measured in at least 1 dimension with the longest diameter  10 mm when measured by spiral computerized tomography (CT, 5-mm slice thickness contiguous) or  20 mm when measured by conventional CT (10-mm slice thickness contiguous). Lesion must be  2 times the size of the slice thickness per Response Evaluation Criteria in Solid Tumors (RECIST). 5. Age > 18 years. 6. Screening laboratory values within the following limits:  ANC >=1500/mL  Platelet count >=100,000/mL  Leukocyte count >=2000/uL  Hemoglobin >= 8.0 g/dL (80g/L) without transfusion within 2 weeks of first dose of test article  Serum creatinine =40%) as assessed by electrocardiogram (ECG), echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan 8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 9. Life expectancy of at least 3 months 10. Written, signed, dated, and witnessed IRB or IEC approved informed consent form (ICF) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of a central nervous system (CNS) malignancy or metastatic disease to the CNS or known, active CNS malignancy (primary or metastatic). 2. More than one prior systemic therapy for mRCC other than sunitinib. 3. Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers. Subjects taking CYP3A4 isoenzyme inhibitors and/or inducers not listed in Appendix are eligible, provided they have been on a stable regimen for at least 4 weeks prior to enrollment. 4. Subjects with a non-healing wound or ulcer. 5. Grade >=3 hemorrhage within the past month. 6. Systolic blood pressure of > 160 mm Hg and/or diastolic pressure > 100 mg Hg (anti-hypertensive medications permitted). 7. AHA Class 3/4 heart disease. 8. QTc interval > 450 msec for males and > 470 msec for females and/or any ventricular arrhythmia and/or any uncontrolled atrial arrhythmia. 9. Subjects receiving anticoagulation with warfarin (therapeutic doses of warfarin for catheter patency are permitted). Low molecular weight (LMW) heparin is permitted. 10. Glycosylated hemoglobin A1c (HbA1c) > 10% despite therapy. 11. History of pulmonary hypertension or interstitial lung disease. 12. Subjects receiving immunosuppressive agents within 4 weeks of the screening visit. Replacement doses of corticosteroids and topical/inhaled steroids are permitted. 13. Chronic viral/bacterial/fungal illnesses such as human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. 14. Active infection(s), active antimicrobial therapy or serious intercurrent illness. 15. Subjects with a ?currently active? second malignancy other than non-melanoma skin cancers. Subjects are not considered to have a ?currently active? malignancy if they have completed anti-cancer therapy and are considered by their physician to be at less than 30% risk of relapse. 16. Pregnant or nursing women, women who are of childbearing potential (biologically capable of becoming pregnant) who are not using a medically acceptable contraceptive method, or men who are not using a medically acceptable contraceptive method with partners of childbearing potential. 17. Subjects who do not agree to use medically acceptable contraceptive methods for 3 months after their last dose of Torisel therapy. 18. Any other major illness that, in the investigator?s judgment, will substantially increase the risk associated with the subject?s participation in this study. 19. Known hypersensitivity to any of the components in the Torisel infusion products or other medical reasons for not being able to receive adequate premedication (for example, antihistamines).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PFS rate at 6 months;Secondary Objective: ORR (RECIST criteria) Duration of response Duration of stable disease Toxicity PFS OS Quality of life (EORTC QLQ C-30) Biological/molecular correlates (TBD);Primary end point(s): Medical history Physical Examination CBC (including WBC with differential) Serum electrolytes Serum chemistry Coagulation tests HbA1c Routine urinalysis CT of chest, abdomen and pelvis ECG/ECHO or MUGA Chest x-ray Vital signs Adverse events Concomitant medications | — |
Countries
Italy
Outcome results
None listed