A Multi-Center, Randomized, Phase 3 Study of Adjuvant Oncophage versus Observation in Patients with High Risk of Recurrence after Surgical Treatment of Renal Cell Carcinoma

• Conditions: Renal cell carcinoma stage unspecified

• Registration Number: EUCTR2004-004572-36-AT
• Lead Sponsor: Antigenics Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-08-25
• Last Update Posted: 22 April 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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).;Secondary Objective: Determine whether patients randomized to receive adjuvant HSPPC-96 have improved overall survival as compared to patients in observation (no adjuvant treatment).<br><br>Fully characterize the safety profile of HSPPC-96.;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.<br><br>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.