E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with metastatic RCC |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050018 |
E.1.2 | Term | Renal cancer metastatic |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
|
E.2.2 | Secondary objectives of the trial |
ORR (RECIST criteria) Duration of response Duration of stable disease Toxicity PFS OS Quality of life (EORTC QLQ C-30) Biological/molecular correlates (TBD) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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: &#61607; ANC >=1500/mL &#61607; Platelet count >=100,000/mL &#61607; Leukocyte count >=2000/uL &#61607; Hemoglobin >= 8.0 g/dL (80g/L) without transfusion within 2 weeks of first dose of test article &#61607; Serum creatinine <= 2.0 X ULN &#61607; Total bilirubin <= 1.5 X ULN &#61607; AST and ALT <=3 X ULN [&#61603;5 X ULN if liver metastases are present] &#61607; Fasting serum cholesterol <=350 mg/dL (9.0 mmol/L) &#61607; Fasting serum triglycerides <=400 mg/dL (4.56 mmol/L) &#61607; Fasting hemoglobin A1c (HbA1c) < 10% (therapy permitted) &#61607; PTT/INR or PT < 1.3 x ULN &#61607; Urinalysis within normal limits
6. Metabolic, thyroid, and pancreatic function within laboratory limits of normal
7. Adequate cardiac (left ventricular ejection fraction >=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) |
|
E.4 | Principal 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 investigators judgment, will substantially increase the risk associated with the subjects 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). |
|
E.5 End points |
E.5.1 | 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 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 50 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |