A Study of Atezolizumab (Anti-PD-L1 antibody) as Adjuvant Therapy in Patients with Renal Cell Carcinoma at High Risk of Developing Metastasis Following Nephrectomy
- Conditions
- Patients at high risk of Renal Cell Carcinoma (RCC) recurrence after nephrectomy and select patients with metastatic RCC recurrence who have undergone complete metastasectomyMedDRA version: 11.0 Level: HLT Classification code 10038408 Term: Renal cell carcinomas System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001881-27-CZ
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 764
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of <= 1
- Able to comply with the study protocol, in the investigator’s judgment
- Pathologically confirmed RCC with a component of either clear cell histology or sarcomatoid histology that has not been previously treated in the adjuvant or neoadjuvant setting. Patients enrolled based on localized disease include those with T2 Grade 4, T3a Grade 3-4, T3b/c any grade, T4 any grade and TxN + any grade are eligible
- Patients with pulmonary (treated with sub-lobar or lobar resection), lymph node, or soft-tissue metachronous recurrence of disease occurring greater than 12 months following nephrectomy who undergo complete resection and have no evidence of disease following metastasectomy are also eligible. Patients with resected CNS, bone or adrenal metastasis are not eligible
- Patients with synchronous isolated solitary ipsilateral or contralateral adrenal and lung metastases treatable with a sub-lobar or lobar resection within 12 weeks of nephrectomy are eligible
- Radical or partial nephrectomy with lymphadenectomy in select patients
- Representative formalin-fixed paraffin-embedded resected tumor specimens in paraffin blocks or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor programmed death ligand-1 (PD-L1) expression prior to study enrollment
- Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization. Confirmation of disease-free status will be assessed by an independent central radiologic review of imaging data
- Absence of brain metastasis, as confirmed by a negative CT with contrast or magnetic resonance imaging scan of the brain, no more than 4 weeks prior to randomization for those enrolled based upon a metastasectomy
- Full recovery from nephrectomy or metastasectomy within 12 weeks from randomization following surgery
- Adequate hematologic and end-organ function within 28 days prior to randomization
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period for at least 5 months after the last dose of study drug, and agreement to refrain from donating eggs during this same period
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 230
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 534
- Bilateral synchronous tumors with inheritable forms of RCC including von Hippel-Lindau
- Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
- Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days or five half-lives of the investigational agent, whichever is longer, prior to enrollment
- Central nervous system metastases or leptomeningeal disease
- Malignancies other than RCC within 5 years prior to Cycle (C) 1, Day (D) 1. Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death <5% at 5 years) are eligible provided they meet all of the following criteria: Malignancy treated with expected curative intent (e.g., adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated surgically with curative intent). No evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers
- Life expectancy of < 24 weeks
- Pregnancy or lactation, or intending to become pregnant during the study
- Serum albumin < 2.5 g/dL
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- History of autoimmune diseases. Patients with a history of autoimmune-related hypothyroidism and Type 1 diabetes mellitus on a stable dose of hormone or insulin replacement may be eligible for this study. Patients with well controlled, limited autoimmune skin conditions may be eligible.
- Patients with prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class III or greater), myocardial infarction within 3 months prior to initiation of study treatment, unstable arrhythmias, or unstable angina
- Patients with a known left ventricular ejection fraction <40%.
- Positive test for human immunodeficiency virus
- Patients with active hepatitis B and hepatitis C
- Active tuberculosis
- Severe infections within 4 weeks prior to initiation of study treatment
- Receipt of therapeutic oral or intravenous antibiotics within 2 weeks prior to initiation of study treatment
- Major surgical procedure within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
- Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicate
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the efficacy of adjuvant treatment with atezolizumab in patients at high risk of RCC recurrence as determined by Independent Review Facility (IRF)-assessed disease free survival (DFS);<br> Secondary Objective: • To evaluate other measures of efficacy of adjuvant treatment with atezolizumab<br> • To evaluate the safety and tolerability of atezolizumab in the adjuvant setting<br> • To characterize the Pharmacokinetic (PK) profile of atezolizumab<br> • To evaluate the immune response to atezolizumab<br> • To explore the potential relationship of the immunogenic response and PK profile<br> ;Primary end point(s): • Independent Review Facility (IRF)-assessed disease free survival (DFS);Timepoint(s) of evaluation of this end point: • Up to 88 months
- Secondary Outcome Measures
Name Time Method