Kidney Cancer
Conditions
Keywords
clear cell renal cell carcinoma, stage I renal cell cancer, stage II renal cell cancer, stage III renal cell cancer, stage IV renal cell cancer
Brief summary
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether monoclonal antibody therapy is effective in treating kidney cancer. PURPOSE: This randomized phase III trial is studying monoclonal antibody therapy to see how well it works in treating patients who have undergone surgery for nonmetastatic primary kidney cancer.
Detailed description
OBJECTIVES: Primary * Evaluate the disease-free and overall survival of patients with primary clear cell renal cell carcinoma at high risk for recurrence treated with chimeric monoclonal antibody cG250 (WX-G250) vs placebo in an adjuvant setting. Secondary * Evaluate the safety of these drugs in these patients. * Assess the quality of life of patients treated with this drug. * Perform pharmacokinetic analysis of WX-G250. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to risk criteria and participating centers (US vs Non-US). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive monoclonal chimeric antibody cG250 (WX-G250) IV over 15 minutes once weekly for 24 weeks. * Arm II: Patients receive placebo IV over 15 minutes once weekly for 24 weeks. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Blood samples are collected for pharmacokinetic analysis. Quality of life is assessed at baseline, at weeks 12 and 24 during treatment, and then at 6 months after completion of study treatment. Patients are followed every 3 months during years 1 and 2, every 6 months during years 3 and 4, and then annually during year 5 and thereafter. PROJECTED ACCRUAL: A total of 864 patients out of the expected 856 (428 per treatment arm) were accrued for this trial.
Interventions
BIOLOGICALgirentuximab
Given IV
OTHERplacebo
Given IV
Sponsors
Heidelberg Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed primary clear cell renal cell carcinoma * Meets 1 of the following high risk criteria: * T3a, N0/NX, M0 OR T3b, N0/NX, M0 OR T3c, N0/NX, M0 OR T4, N0/NX, M0 * Any T stage and N + disease and M0 * T1b, N0/NX, M0 OR T2, N0/NX, M0, each with grade ≥ 3 (Fuhrman or any other nuclear grading system with at least 3 grades) * Prior nephrectomy (total or partial) of primary renal cell carcinoma with documented clear cell histology within the past 12 weeks * No evidence of macroscopic or microscopic residual disease PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * Platelet count \> 100,000/mm\^3 * WBC \> 3,000/mm\^3 * Hemoglobin \> 10 g/dL Hepatic * AST and ALT \< 3 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN * Hepatitis B surface antigen (HbsAg) negative * Hepatitis C antibody negative Renal * Creatinine \< 2.0 times ULN Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV I and II negative * No concurrent unrelated illness which can significantly jeopardize patients' clinical status * No active infection * No inflammation * No medical condition or laboratory abnormalities that would preclude study participation * No other malignancies within the past 5 years except surgically cured nonmelanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * More than 5 years since prior immunotherapy * No prior murine or chimeric antibody therapy Chemotherapy * More than 5 years since prior chemotherapy Endocrine therapy * No concurrent corticosteroids above Cushing dose for another disease * Physiologic corticosteroid replacement therapy allowed at discretion of the primary investigator Radiotherapy * More than 5 years since prior radiotherapy Surgery * See Disease Characteristics * No prior organ transplantation Other * No concurrent immunosuppressive agents (e.g., cyclosporine or tacrolimus)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival | Until signs of recurrence or until 360 local DFS events have occurred (median follow-up of 4.5 years) | Disease Free Survival (DFS) calculated from the date of randomization up to and including the date of documented relapse as confirmed by the CT, death or start of new anti-tumor therapy. |
| Overall Survival | After 419 OS events or 60 months after the last patient has been enrolled, whichever is the later (median follow-up of 4.5 years) | Overall Survival (OS) calculated from the date of randomization to the date of death. Patients with no documented death will be censored at the date of their last study evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life - Global Health Status | At 12 months | Quality of life by EORTC Quality of Life Questionnaire-C30 - Global Health Status at 12 months. A high score for the global health status/QoL represents a high QoL with 0 being the minimum and 100 being the maximum. |
| Pharmacokinetics of WX-G250 | Week 8 | Quantitative determination of cG250 (Girentuximab) trough serum profiles at week 8 (steady state concentration). |
Countries
Argentina, Brazil, Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Patients receive monoclonal chimeric antibody cG250 (WX-G250) IV over 15 minutes as a single loading dose of 50 mg (week 1) followed by weekly infusions of 20 mg of WX-G250 (weeks 2-24).
girentuximab: Given IV | 433 |
| Placebo Patients receive placebo IV over 15 minutes once weekly for 24 weeks.
placebo: Given IV | 431 |
| Total | 864 |
Baseline characteristics
| Characteristic | Intervention | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 9.83 | 57.8 years STANDARD_DEVIATION 10.1 | 58.0 years STANDARD_DEVIATION 9.98 |
| Sex: Female, Male Female | 157 Participants | 133 Participants | 290 Participants |
| Sex: Female, Male Male | 276 Participants | 298 Participants | 574 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 164 / 431 | 166 / 424 |
| serious Total, serious adverse events | 36 / 431 | 36 / 424 |
Outcome results
Primary
Disease-free Survival
Disease Free Survival (DFS) calculated from the date of randomization up to and including the date of documented relapse as confirmed by the CT, death or start of new anti-tumor therapy.
Time frame: Until signs of recurrence or until 360 local DFS events have occurred (median follow-up of 4.5 years)
Population: All patients that were enrolled were included in the ITT population used for efficacy analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Disease-free Survival | 192 Participants |
| Placebo | Disease-free Survival | 197 Participants |
p-value: 0.737Log Rank
Primary
Overall Survival
Overall Survival (OS) calculated from the date of randomization to the date of death. Patients with no documented death will be censored at the date of their last study evaluation.
Time frame: After 419 OS events or 60 months after the last patient has been enrolled, whichever is the later (median follow-up of 4.5 years)
Population: All patients that were enrolled were included in the ITT population used for efficacy analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Overall Survival | 91 Participants |
| Placebo | Overall Survival | 90 Participants |
p-value: 1.012Log Rank
Secondary
Pharmacokinetics of WX-G250
Quantitative determination of cG250 (Girentuximab) trough serum profiles at week 8 (steady state concentration).
Time frame: Week 8
Population: Patients who did sign amendment #3 to the study protocol and received their cG250 infusion as scheduled in the study protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Pharmacokinetics of WX-G250 | 8.7 µg/mL | Standard Deviation 5.8 |
Secondary
Quality of Life - Global Health Status
Quality of life by EORTC Quality of Life Questionnaire-C30 - Global Health Status at 12 months. A high score for the global health status/QoL represents a high QoL with 0 being the minimum and 100 being the maximum.
Time frame: At 12 months
Population: Patients still on study who completed the questionnaire
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Quality of Life - Global Health Status | 71 score on a scale | Standard Deviation 21 |
| Placebo | Quality of Life - Global Health Status | 71 score on a scale | Standard Deviation 20 |
Post Hoc
Disease Free Survival (DFS) for Patients With CAIX Score >= 2.6
This analysis includes patients having a CAIX Expression equal or above the CAIX score of 2.6. The CAIX score is determined on the basis of CAIX expression via immunohistochemistry described by a combination of tumor cell extent and staining intensity. Disease Free Survival (DFS) calculated from the date of randomization up to and including the date of documented relapse as confirmed by the CT, death or start of new anti-tumor therapy.
Time frame: Until signs of recurrence or until 360 local DFS events have occurred (median follow-up of 4.5 years)
Population: This analysis includes patients having a CAIX Expression equal or above the CAIX score of 2.6.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Disease Free Survival (DFS) for Patients With CAIX Score >= 2.6 | 20 Participants |
| Placebo | Disease Free Survival (DFS) for Patients With CAIX Score >= 2.6 | 39 Participants |
p-value: 0.022Log Rank