A phase III, multicenter, randomized, placebo-controlled, double-blind 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
- iercelcarcinoomKidney CancerRenal Cell Carcinoma1003836410038430
- Registration Number
- NL-OMON55502
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
- 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. Patient 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 are also eligible. Patients with synchronous adrenal and lung
metastases who have undergone complete resection of residual disease witin 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
- 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
-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 before C1D1
- Any other diseases, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or
condition that contraindicates the use of an investigational drug or that may
affect the interpretation of the results or render the patient at high risk
from treatment complications
- Prior treatment with CD137 agonists, anti-CTLA-4, anti-PD*1, or anti*PD-L1
th
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Investigator-assessed DFS, defined as the time from randomization to the<br /><br>earliest death from any cause or the first documented recurrence event assessed<br /><br>by IRF, defined as any of the following:<br /><br>Local recurrence of RCC<br /><br>New primary RCC<br /><br>Distant metastasis of RCC<br /><br><br /><br></p><br>
- Secondary Outcome Measures
Name Time Method <p>• Overall survival defined as the time from randomization to death from any<br /><br>cause<br /><br>• Investigator assessed DFS in patients with PD-L1 expression status IC1/2/3<br /><br>• Independent Review Facility (IRF)-assessed DFS<br /><br>• IRF assessed DFS in patients with PD-L1 expression status IC1/2/3<br /><br>• IRF-assessed event-free survival (EFS)<br /><br><br /><br>• Disease-specific survival, defined as the time from randomization to death<br /><br>from RCC<br /><br>• Distant metastasis-free survival, defined as the time from randomization to<br /><br>the date of diagnosis of distant (i.e., non-locoregional)<br /><br>metastases assesed by the investigator or death from any cause<br /><br>• 3-year IRF-assessed DFS rate, defined as the probability of patients alive<br /><br>and recurrence free at Year 3 after randomization<br /><br>• 3-year investigator-assessed DFS rate</p><br>