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

Phase 1

• Conditions: Patients at high risk of Renal Cell Carcinoma (RCC) recurrence after nephrectomy and select patients with metastatic RCC recurrence who have undergone complete metastasectomy; MedDRA version: 11.0Level: HLTClassification code 10038408Term: Renal cell carcinomasSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001881-27-IT
• Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 24 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 764

Inclusion Criteria

- 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

Exclusion Criteria

- 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 halflives
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 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 therapeutic antibody or pathway-targeting agents
- Treatment with systemic immunostimulatory agents within 6 weeks or
five half-lives of the drug, whichever is sho

Study & Design

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