E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal cell carcinoma of the clear cell type after nephrectomy and no evidence of residual disease |
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E.1.1.1 | Medical condition in easily understood language |
Patients with kidney cancer after complete removal of kidney cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038415 |
E.1.2 | Term | Renal cell carcinoma stage unspecified |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To evaluate disease-free survival and overall survival on cG250 therapy as compared to placebo |
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E.2.2 | Secondary objectives of the trial |
To evaluate quality of life and safety. To perform a population pharmacokinetic analysis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Prior (partial or total) nephrectomy of primary renal cell carcinoma with documented clear cell histology
2. No evidence of macroscopic and microscopic residual disease (enlarged lymph nodes schould be removed)
3. Patients diagnosed of having one of the following (referring to TNM classification, 6th edition UICC, 2002):
- Risk group I: T3aN0/XM0 or T3bN0/XM0 or T3cN0/XM0 or T4N0/XM0
- Risk group II: any T stage and N+ disease and M0
- Risk group III: T1bN0/XM0 or T2N0/XM0, each with grading >=3 (Fuhrman or any other nuclear grading system with at least 3 grades)
4. ECOG of 0-1 (see Appendix II)
5. Not more than 12 weeks between date of nephrectomy and randomization
6. Negative HIV I and II test
7. Negative Hepatitis B surface antigen (HbsAg) or Hepatitis C antibody result
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E.4 | Principal exclusion criteria |
1. Pre-exposure to murine/chimeric antibody therapy
2. Patients who require or are likely to require systemic corticosteroids above Cushing doses for another disease (patients on physiologic corticosteroid replacement therapy may be included in the study at the discretion of the investigator)
3. Prior organ transplantation
4. Laboratory values obtained <= 3 weeks before randomization:
- White blood cells (WBC) <= 3.0 x 108/dl
- Platelet count <= 100 x 108/dl
- Hemoglobin <= 6.2 mmol/l (equals 10 g/dl)
- Total bilirubin >= 1.5 x upper limit of normal (ULN)
- ASAT, ALAT >= 3 x ULN
- Serum creatinine >= 2 x ULN
5. History of prior malignancies within the last 5 years, except for surgically-cured non-melanoma skin cancer, or cervical carcinoma in situ
6. Prior radiation or immunotherapy or chemotherapy within the last 5 years
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objectives are:
- to evaluate the disease-free survival on cG250 therapy as compared to placebo
- to evaluate overall survival on cG250 therapy as compared to placebo.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
disease-free survival: at a specified number of events (please refer to protocol)
overall survival: After 419 OS events or 60 months after the
last patient has been enrolled, whichever is the later |
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E.5.2 | Secondary end point(s) |
- assess quality of life in the treatment and placebo arms (EORTC)
- evaluate safety
- perform a population pharmacokinetic analysis that provides an understanding of cG250 pharmacokinetics in patients receiving cG250 as adjuvant therapy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Quality of life: baseline, weeks 12 and 24, after 12 months
Adverse events: baseline, during treatment, until 30 days after treatment
Laboratory values: baseline, weeks 4, 8, 12, 16, 20, 24 during treatement, after 9 months (hematology and chemistry panel)
Population pharmacokinetic analysis: baseline, weeks 4, 8, 12, 16, 20, 24 during treatement, after 9 months |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 | No |
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 |
Argentina |
Brazil |
Canada |
Czech Republic |
Finland |
France |
Germany |
Norway |
Poland |
Russian Federation |
Sweden |
Ukraine |
United Kingdom |
United States |
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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
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last visit / last patient |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |