E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal cell carcinoma stage unspecified
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MedDRA Classification |
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 determine whether patients randomized to receive adjuvant, autologous HSPPC-96 treatment after surgical resection of locally advanced renal cell carcinoma have improved recurrence-free survival as compared to patients in observation (no adjuvant treatment). |
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E.2.2 | Secondary objectives of the trial |
Determine whether patients randomized to receive adjuvant HSPPC-96 have improved overall survival as compared to patients in observation (no adjuvant treatment).
Fully characterize the safety profile of HSPPC-96. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Pre Surgery Inclusion Criteria 1. Primary-intact resectable renal cell carcinoma, eligible for nephrectomy with curative intent. 2. Tumour size is 5cm or more OR macroscopic nodes OR renal vien thrombus OR vena cava thrombus by radiologic evaluation to meet definition of at least stage I disease. 3. Performance status (ECOG scale) is 1 or less and life expectancy of greater than 3 months. 4. Age 18 years or above. 5. If randomized to HSPPC-96 treatment arm, male or female patients of child bearing potiential must agree to use contraception during the Tomour Evaluation phase of the study and for one month after the last vaccination. 6. Signed written informed consent must be obtained and documented according to ICH-GCP, the local regulatory requirements and the rules followed at each institution. Post-surgery Inclusion Criteria (must be completed within 5 weeks of surgery) 1. Confirmation of renal clear cell histology with > 25% clear cell features as per pathological report determination. 2. Tumour stage, determined using 2002 AJCC TNM staging, considered to be of high risk for recurrence must meet one of the following stage definitions: - Stage I, high grade (Fuhrman grade 3 and 4) - Stage II high grade (Fuhrman grade 3 and 4), OR - Stage III, OR - Stage IV non-metastatic 3. Availability of at least 4 doses of autologous HSPPC-96 (at least 4 injections) for clinical administration produced from the tumour sample provided. 4. Adequate haematopoietic function (granulocytes NLT 1 x 10 9/L; platelets NLT 100 x 10 9/L, haemoglobin > 10 g/L. 5. Adequate renal and hepatic function as per: - Creatinine NMT 1.5 x upper limit of normal - Alkaline phosphatase < 2 x upper limit of normal - Total bilirubin NMT 2 x upper limit of normal - AST and ALT NMT 2 x the upper limit of normal 6. Negative serology tests for HIV-1, HIV-2, HTLV-1, Hepatitis B and Hepatitis C. 7. Performance status (ECOG scale) is 1 or less and life expectancy of greater than three months. 8. Adequate cardiac function maximum of class II per NYHA. 9. Women of childbearing potential must have a negative urine or serum pregnancy test before randomization.
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E.4 | Principal exclusion criteria |
Pre-surgery exclusion criteria: 1. Multifocal tumour of the kidney or bilateral kidney tumours. 2. Prior surgery or chemo-, hormonal-, immuno- or radiotherapy for renal cell cancer. 3. History of primary or secondary immunodeficiency, or patients using immunosuppressive drugs, e.g. systemic corticosteroids, cyclosporin A or any autoimmune disorder. 4. Current malignancies of any type in other sites. 5. History or other malignancy within the last five years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin. 6. Embolization of the renal artery prior to nephrectomy. 7. Known distant metastases, including enlarged distant lymph nodes on radiologic evaluation, either confirmed as malignant via biopsy or will be assumed malignant if not assessed pathologically. 8. Active uncontrolled infection or other serious medical illnesses. 9. Previous splenectomy or intended splenectomy at the time of surgery. 10. Intended use of any other investigational product within four weeks prior to randomization and throughout the Tumour evaluation Phase of the Study.
Post Surgery Exclusion Criteria (must be completed within 5 weeks of surgery) 1. Clinical evidence of metastatic or residual renal cell carcinoma as documented on any of the following required scans: - Abdominal CT scan (with oral and IV contrast) - Pelvic CT scan (with oral and IV contrast) - Chest CT scan (without contrast) 2. Splenectomy performed during nephrectomy. 3. Use of any other investigational product for four weeks prior to randomization and throughout the Tumour Evaluation Phase of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint of recurrence-free survival (RFS): All patients will receive scans of the chest, abdomen and pelvis to determine disease status at baseline (post surgery eligibility time point) and during the tumour evaluation phase.
All images of all randomized patients will be collected in a prospective fashion and reviewed by an independent Clinical Events Committee (CEC) to support the primary study endpoint of RFS. |
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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 | 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 | Information not present in EudraCT |
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 |
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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 | 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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | Information not present in EudraCT |
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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After disease recurrence, follow-up for overall surival will occur in three-month intervals up to six years after randomization of the last patient, or until the specified number of events needed for final analysis for overall survival have been achieved, whichever comes later. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |