Study of Atezolizumab + Bevacizumab in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma

NCT02724878 | Completed Phase 2 Results DMC

• 1 other identifier: 15-592
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is studying the combination of Atezolizumab and Bevacizumab as a possible treatment for Advanced Non-Clear Cell Kidney Cancer.

Conditions

Advanced Non-Clear Cell Kidney Cancer

Keywords

Kidney Cancer

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate

  The best overall response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesion: (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.

  Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. The median (range) of treatment time was 9.5 (1-42) cycles, thus participants were assessed up to ~32 months .

Secondary Outcomes (19)

• Best Overall Response Rate by Histological Subtypes

  Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. The median (range) of treatment time was 9.5 (1-42) cycles, thus participants were assessed up to ~32 months

• Percentage of Participants With Treatment-related Adverse Events

  Adverse events are measured continuously on treatment and up to thirty days after going off treatment (up to ~32 months).

• Duration of Response

  Measured every 6 weeks for the first 24 weeks and then every 12 weeks while on treatment. Off-treatment, patients are followed every 6 months for up to two year. Participants were followed up to 32 months.

• Immune Related Best Overall Response Rate

  Measured every 6 weeks while on treatment. Off-treatment, patients are followed every 6 months for up to two year. Participants were followed up to 32 months.

• Median Progression Free Survival

  Participants followed for up to 32 months.

Study Arms (1)

Bevacizumab And Atezolizumab Combination

EXPERIMENTAL

1200 mg of Atezolizumab intravenously x 3 weeks 15 mg/kg of Bevacizumab intravenously x 3 weeks. One cycle will be 3 weeks in duration.

Drug: Bevacizumab; Drug: Atezolizumab

Interventions

Bevacizumab DRUG

Also known as: Avastin

Bevacizumab And Atezolizumab Combination

Atezolizumab DRUG

Also known as: RG-7446

Bevacizumab And Atezolizumab Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Unresectable advanced or metastatic non-clear cell RCC to include but not limited to:
• Papillary RCC, any type
• Unclassified RCC
• Translocation RCC
• Chromophobe RCC
• Collecting duct RCC
• Medulary RCC
• Clear cell RCC or any histology with \> 20% sarcomatoid features will be eligible.
• Other non-clear cell histologies that are not included above need to be discussed with the PI.
• Request for formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens if available and willingness of the participant to undergo mandatory fresh tumor biopsy unless determined medically unsafe or not feasible. A note from the study team should be provided documenting availability of tissue. If a target lesion is biopsied at screening, this lesion must be followed as non-target lesion after the biopsy unless it is the patient's only target lesion. If there is only one target lesion, it should be followed as a target lesion regardless.
• The archival specimen should contain adequate viable tumor tissue.
• The specimen may consist of a tissue block (preferred and should contain the highest grade of tumor) or at least 30 unstained serial sections. Fine-needle aspiration, brushings, cell pellet from pleural effusion, bone marrow aspirate/biopsy are not acceptable.
• Fresh tumor biopsy at progression will be required in cases where patients experience relapse after an initial response if medically safe.
• Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.

You may not qualify if:

• Prior treatment with CD137 agonists, anti- cytotoxic T-lymphocyte-associated protein 4, anti-PD-1, or anti-PDL1 therapeutic antibody or pathway targeting agents.
• Prior IFNα or IL-2 is allowed following 4 week washout from treatment end date.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 4 weeks of enrollment.
• Prior therapy with bevacizuamab.
• Thrombologic event within 3 weeks of treatment start date, unless stable on anticoagulation with LMWH or Factor Xa inhibitor for at least 2 weeks.
• Treatment with systemic immunosuppressive medications including but not limited to: prednisone, dexamethasone, cyclosporin, azathioprine, methotrexate, thalidomide, anti- tumor necrosis factor (TNF) agents, hydroxychloroquine within 2 weeks of first study dose.
• Patients who have received acute, low-dose systemic immunosuppressant medications may be enrolled.
• Patients with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled.
• The use of inhaled, topical intraocular, or intra articular corticosteroids or, mineralocorticoids are allowed.
• Radiotherapy for RCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to the initiation of study treatment. Stability must be confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) imaging and/or treating investigator determination.
• Malignancies other than RCC within 2 years of first study treatment with the exception of those with negligible risk of metastases or death (included but not limited to carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma, or other malignancy not deemed to impact that patients 5-year life expectancy).
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
• Known hypersensitivity to any component of the atezolizumab product.
• History of autoimmune disease including: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on thyroid replacement hormone or those with autoimmune dermatologic conditions not requiring the use of prednisone \> 10 mg or equivalent are eligible.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Genentech, Inc.: collaborator

Study Sites (4)

University of California, San Diego Moores Cancer Center

La Jolla, California, 92037, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Related Publications (2)

• Saliby RM, El Zarif T, Bakouny Z, Shah V, Xie W, Flippot R, Denize T, Kane MH, Madsen KN, Ficial M, Hirsch L, Wei XX, Steinharter JA, Harshman LC, Vaishampayan UN, Severgnini M, McDermott DF, Lee GM, Xu W, Van Allen EM, McGregor BA, Signoretti S, Choueiri TK, McKay RR, Braun DA. Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma. Cancer Immunol Res. 2023 Aug 3;11(8):1114-1124. doi: 10.1158/2326-6066.CIR-22-0996.

  PMID: 37279009 BACKGROUND

• McGregor BA, McKay RR, Braun DA, Werner L, Gray K, Flaifel A, Signoretti S, Hirsch MS, Steinharter JA, Bakouny Z, Flippot R, Wei XX, Choudhury A, Kilbridge K, Freeman GJ, Van Allen EM, Harshman LC, McDermott DF, Vaishampayan U, Choueiri TK. Results of a Multicenter Phase II Study of Atezolizumab and Bevacizumab for Patients With Metastatic Renal Cell Carcinoma With Variant Histology and/or Sarcomatoid Features. J Clin Oncol. 2020 Jan 1;38(1):63-70. doi: 10.1200/JCO.19.01882. Epub 2019 Nov 13.

  PMID: 31721643 RESULT

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

Bevacizumab; atezolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Toni Choueiri
• Organization: Dana-Farber Cancer Institute

toni_choueiri@dfci.harvard.edu

617-632-5456

Study Officials

• Toni Choueiri, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Toni K. Choueiri, MD

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 31, 2016
• Study Start: July 15, 2016
• Primary Completion: November 13, 2019
• Study Completion: December 31, 2024
• Last Updated: February 13, 2025
• Results First Posted: April 21, 2021

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (4)