E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Recurrent or Metastatic Clear-Cell Renal Cell Carcinoma |
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MedDRA Classification |
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 |
The principal objective of the trial is to compare the progressive disease rate at 16 weeks post-randomization of subjects receiving GW786034 or placebo and to determine the stable disease rate at 12 weeks in the Lead-in phase.
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E.2.2 | Secondary objectives of the trial |
- To Assess progression-free survival (PFS) and duration of response in subjects receiving GW786034. - To Determine the objective response rate (complete and partial responses) at 12 weeks in the Lead-in phase. - To Evaluate the safety and tolerability of GW786034 in this subject population. - To characterize the population pharmacokinetics (PK) parameters of GW786034 when administered daily in this population including an assessment of significant covariates and to assess the potential relationships between the pharmacokinetics of GW786034 and relevant safety and efficacy endpoints. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Histologically or cytologically confirmed diagnosis of renal cell carcinoma of predominantly clear-cell histology (excluding chromophobe, papillary, collecting duct, and undifferentiated tumors) which is metastatic or locally recurrent. - Either no prior systemic therapy or failed only 1 prior cytokine-based or bevacizumab-based therapy (i.e. Interleukin-2 (IL-2), Interferon-alpha, or a combination regimen of IL-2 and Interferon-alpha, or bevacizumab alone or in combination with cytokine therapy). If subjects have received prior therapy, they must have documented evidence by RECIST criteria of disease progression based on radiographic imaging. - Evidence of documented measurable disease by RECIST criteria (lesions that can be accurately measured in at least one dimension with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan). - Male or female at least 21 years of age. A woman is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, a bilateral ophorectomy (ovariectomy), a bilateral tubal ligation or is post-menopausal. b. Childbearing potential, has a negative serum pregnancy test at Screening Period and Day1, and agrees to use adequate contraception (intrauterine device (IUD) with a documented failure rate of less than 1% per year, Vasectomized partner who is sterile prior to the female subject’s entry and is the sole sexual partner for that female, Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, through the clinical trial, and for at least 21 days after the last dose of investigational product, Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide). A man with a female partner of childbearing potential, is eligible to enter and participate in the study if he has either had a prior vasectomy or agrees to use effective contraception during the study. - ECOG Performance Status (PS) of 0 or 1. - Adequate bone marrow function: ANC ≥ 1,000/mm3 (1 X 109/L), Platelet count ≥ 75,000/mm3 (75 X 109/L). - Adequate hepatic function: total bilirubin ≤ 1.5 X ULN, AST (SGOT) ≤ 3.0 X ULN, ALT (SGPT) ≤ 3.0 X ULN. - Adequate renal function as determined by the following tests: Calculated creatinine clearance ≥ 40 mL/min as measured by Cockcroft and Gault Formula for estimated Creatinine Clearance (CLcr) and Urine protein < 1.0 grams/24-hrs. - PT/INR/PTT within 1.2 X ULN. - Able to swallow and retain oral medications. - before patient registration, written informed consent given .
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E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Received prior non-cytokine or non-bevacizumab therapies (e.g., SU011248, PTK- 787, thalidomide, gefitinib, sorafenib (BAY 43-9006), or vaccines). 2. Received chemotherapy for renal cell carcinoma. 3. Has had any major surgery, radiotherapy, or immunotherapy within the last 28 days and/or not recovered from prior therapy. 4. History of hypercalcemia (corrected serum calcium above institution normal) within two months of start of therapy. 5. Women who are pregnant or lactating. 6. Poorly controlled hypertension (SBP of 140 mmHg or higher, or DBP of 90 mmHg or higher). Initiation or adjustment of BP medication is permitted prior to study entry provided that subject has an averaged of three BP readings at a visit less than 140/90 mmHg. These readings need to be collected prior to enrolment. 7. QTc prolongation defined as a QTc interval greater than or equal to 480 msecs or other significant ECG abnormalities. 8. Has Class II, III or IV heart failure as defined by the NYHA functional classification system. A subject who has a history of Class II heart failure and is asymptomatic on treatment may be considered eligible. 9. Any history of cerebrovascular accident [CVA]. 10. History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks. 11. History of venous thrombosis in last 12 weeks. 12. Current use of therapeutic warfarin. Low molecular weight heparin and prophylactic low-dose warfarin are permitted. PT/PTT must meet the inclusion criteria. 13. Use of antiplatelet agents other than aspirin (≤ 325 mg/day). 14. Leptomeningeal or brain metastases. 15. Prior history of malignancies other than renal cell carcinoma (except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or the subject has been free of any other malignacies for > 5 years). 16. Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject safety or obtaining informed consent. 17. History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs. Has any unresolved bowel obstruction or diarrhea. 18. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 19. Is on any specifically prohibited medication or requires any of these medications during treatment with GW786034. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Progressive disease rate, defined as the percentage of all randomized subjects with progressive disease 16 weeks after randomization. • Stable disease rate in the Lead-in Phase, defined as the number of subjects having stable disease (SD) after 12 weeks of therapy, divided by the total number of subjects enrolled. This endpoint will be assessed at the interim analysis. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
randomised discontinuation design (open-label then double-blinded) |
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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 | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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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 | 0 |
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 | 0 |