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

• Register: EUCTR
• Last refreshed on: 9 January 2023
• Main ID: EUCTR2016-001881-27-FR
• Date of registration: 21/03/2017
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 03/07/2017
• Target sample size: 664
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001881-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Serbia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

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. 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 at the time 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

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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 464

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 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 randomization, 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 randomization
- Receipt of therapeutic oral or intravenous antibiotics within 2 weeks prior to randomization
- Major surgical procedure within 4 weeks prior to randomization 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 therapeutic antibody or pathway-targeting agents



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

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: 11.0 Level: HLT Classification code 10038408 Term: Renal cell carcinomas System Organ Class: 100000004864

Intervention(s)

Product Name: atezolizumab
Product Code: RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: • To evaluate other measures of efficacy of adjuvant treatment with atezolizumab
• To evaluate the safety and tolerability of atezolizumab in the adjuvant setting
• To characterize the Pharmacokinetic (PK) profile of atezolizumab
• To evaluate the immune response to atezolizumab
• To explore the potential relationship of the immunogenic response and PK profile

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)

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(s)

Secondary end point(s): 1. Overall survival
2. Investigator-assessed DFS
3. IRF-assessed DFS in patients with PD-L1 IHC IC 1/2/3 expression
4. Investigator-assessed DFS in patients with IC1/2/3
5. Disease specific survival
6. Distant metastasis-free survival
7. Three year IRF-assessed DFS rate
8. Three year investigator-assessed DFS rate
9. Incidence, nature, and severity of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
10. Changes in vital signs and clinical laboratory results
11. Serum concentration of atezolizumab at specified timepoints
12. Incidence of anti-therapeutic antibodies (ATA) against atezolizumab
13. Relationship between detectable ATA incidence and PK endpoints

Timepoint(s) of evaluation of this end point: 1-10. Up to 88 months
11-12. C1D1, C2D1, C3D1, C4D1, C8D1, treatment discontinuation visit, and >=90 days (up to 120 days) after last dose of atezolizumab
13. Up to 120 days after the last dose of atezolizumab

Secondary ID(s)

WO39210

2016-001881-27-AT

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 03/07/2017
Contact: