| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| first-line treatment for advanced renal cell carcinoma |
|
| 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 | 10050513 |
| E.1.2 | Term | Metastatic renal cell carcinoma |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary endpoint is a comparison of independently assessed progression free survival of subjects with clear
cell type renal cell carcinoma (all risk groups) treated with bevacizumab + temsirolimus (experimental) versus
bevacizumab + interferon-alfa (control) in subjects with advanced renal cell carcinoma. |
|
| E.2.2 | Secondary objectives of the trial |
Safety
Investigator assessed progression free survival.
Objective response rate (CR + PR) per RECIST (independently assessed)
Overall survival |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Male or female subjects >=18 years.
Subject with histologically and/or cytologically confirmed, advanced (stage IV or recurrent) RCC, for whom a
majority component of conventional clear-cell type is mandatory. (Subjects with predominantly papillary or
sarcomatoid features, and subjects with chromophobe, oncocytoma, collecting duct tumors, Bellini tumors or
transitional cell carcinoma are not allowed.)
At least 1 measurable lesion (per RECIST).
Karnofsky Performance Status ³ 70.
Screening laboratory values within the following parameters:
ANC: >1.5 x 109/L (1500/mm3)
Platelet count >=100x 109/L (100,000/mm3)
Hemoglobin ≥8.0 g/dL (80g/L) without transfusion within 2 weeks
of first dose of test article
Serum creatinine <= 1.5 x ULN
Total bilirubin <=1.5 x ULN
AST and ALT <=2.5xULN [<=5 x ULN with liver metastases]
Fasting serum cholesterol <=350 mg/dL (9.0 mmol/L)
Fasting serum triglycerides <= 400 mg/dL (4.56 mmol/L)
HgbA1c < 10% (optimal therapy permitted)
INR and PTT &#8804;1.5 (Anticoagulation is allowed if target INR <3 and INR is therapeutic on a
stable dose of a coumarin type anticoagulation, or if the subject is on a stable dose of LMW heparin for
>2 weeks at time of randomization.)
QTc interval <450 msec for males and <=470 msec for females.
Life expectancy of at least 12 weeks.
Signed and dated institutional review board (IRB) or independent ethics committee (IEC) approved informed
consent form before any protocol-specific screening procedures. |
|
| E.4 | Principal exclusion criteria |
1. Prior systemic treatment for RCC in the neoadjuvant, adjuvant or metastatic setting. Prior treatment with
bevacizumab, temsirolimus, sirolimus, IFN, sunitinib or sorafenib, for any indication.
2. Evidence of current or prior central nervous system (CNS) metastases or any imaging abnormality indicative
of CNS metastases or spinal cord compression.
3. Major surgery (incl. open biopsy) or radiation therapy within 28 days prior to randomization. (Palliative
radiotherapy to painful bone lesions is allowed within 14 days prior to randomization). Subject must have
recovered from prior surgery and radiation.
4. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days
prior to randomization.
5. Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, II, or IV), angina
pectoris requiring nitrate therapy, or myocardial infarction within the last 6 months;
6. Inadequately controlled hypertension (defined as a blood pressure of &#8805; 150 mmHg systolic and/or
&#8805; 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive
encephalopathy.
7. History of stroke or transient ischemic attack within 6 months prior to randomization
8. Significant vascular disease (e.g., aortic aneurysm, aortic dissection), or symptomatic peripheral vascular
disease
9. Known congenital long QT syndrome, history of torsades de pointes or ventricular tachycardia.10. Known pulmonary hypertension or pneumonitis.
11. More than 1 episode of DVT/PE within the last 6 months.
12. Evidence or history of bleeding diathesis or coagulopathy.
13. Chronic daily aspirin >325 mg/day or clopidogrel (>75 mg/day)
14. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to
randomization
15. Any of the following serious, non-healing conditions: wound, ulcer, or bone fracture
16. Proteinuria at screening as demonstrated by either:
- Urine dipstick >=2+ (subjects discovered to have a >= 2+ proteinuria on dipstick urinalysis at baseline
should undergo 24-hour urine collection and must demonstrate <=1g of protein in 24 hours to be eligible.
- 24-hour urine collection demonstrates >=1g of protein in 24 hours.
17. Immunocompromised subjects, including known seropositivity for human immunodeficiency virus (HIV), or
current or chronic hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B
surface antigen [HbsAg] or antibody to hepatitis C virus [anti HCV] with confirmatory testing. Note: Testing
is not mandatory to be eligible for the study.)
18. Chronic treatment with corticosteroids (prednisone &#8805; 12.5 mg/day or dexamethasone &#8805; 2 mg/day) excluding
inhaled steroids.
19. Pregnant or nursing women, women of childbearing potential not using a medically acceptable contraceptive
method, or men not using a medically acceptable contraceptive method with partners of childbearing potential.
A woman of childbearing potential is defined as a woman who is biologically capable of becoming pregnant.
Subjects (men and women) must agree to use medically accepted contraceptive methods for 12 weeks after the
last dose of study drug.
20. Known hypersensitivity to any component of the test articles or excipients, or documented medical condition
that would prohibit adequate pre-medication with antihistamine.
21. Current active second malignancy other than non-melanoma skin cancers and clinically localized prostate
cancer. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer
therapy and are disease-free at least 5 years.
22. Any other significant medical illness, or medically significant abnormal laboratory finding that would, in the
investigator’s judgment, make the subject inappropriate for this study, or would increase the risk associated
with the subjects participation in the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is a comparison of independently assessed progression free survival of subjects with clear
cell type renal cell carcinoma (all risk groups) treated with bevacizumab + temsirolimus (experimental) versus
bevacizumab + interferon-alfa (control) in subjects with advanced renal cell carcinoma. |
|
| 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 | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| esploratorio: valutazioni relative alla salute EQ-5D e FKSI-15 |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 100 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| La fine dello studio coincide con la morte (o ritiro del consenso) dell`ultimo soggetto, o quando lo sponsor decida di terminare lo studio |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
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