Capecitabine and Bevacizumab With or Without Atezolizumab in Treating Patients With Refractory Metastatic Colorectal Cancer

NCT02873195 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: RU021416INCI-2016-01263P30CA015083
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 10

Brief Summary

This randomized phase II trial studies how well capecitabine and bevacizumab with or without atezolizumab work in treating patients with colorectal cancer that is not responding to treatment and has spread to other places. Immunotherapy with monoclonal antibodies, such as atezolizumab and bevacizumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving atezolizumab with capecitabine and bevacizumab may be a better way in treating colorectal cancer.

Conditions

Metastatic Colorectal Carcinoma; Recurrent Colorectal Carcinoma; Refractory Colorectal Carcinoma; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The primary comparisons will be superiority of the active treatment for PFS of atezolizumab versus placebo. PFS will be compared between treatment arms using the un-stratified log-rank test at one-sided level of 0.10 and the p-value will be used for decision making. The hazard ratio (HR) for PFS will be estimated using a Cox proportional hazards model and the 95% confidence interval (CI) for the HR will be provided. Kaplan-Meier methodology will be used to estimate the median PFS for each treatment arm, and Kaplan-Meier curves will be produced. Progression is defined as any new lesion or increase by ≥20% of previously involved sites from nadir based on RECIST criteria.

  From randomization to first documentation of disease progression by RECIST v1.1, or death from any cause, assessed up to 20 months

Secondary Outcomes (3)

• Overall Survival (OS)

  From randomization to death due to any cause, assessed up to 20 months

• Objective Response Rate

  Up to 20 months

• The Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event Deemed at Least Possibly Related to Treatment (Toxicity)

  Up to 20 months

Study Arms (2)

Arm I (atezolizumab, bevacizumab, capecitabine)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on day 1, bevacizumab IV over 30-90 minutes on day 1, and capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Atezolizumab; Biological: Bevacizumab; Drug: Capecitabine; Other: Laboratory Biomarker Analysis

Arm II (placebo, bevacizumab, capecitabine)

ACTIVE COMPARATOR

Patients receive placebo IV over 30-60 minutes on day 1, bevacizumab IV over 30-90 minutes on day 1, and capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Drug: Capecitabine; Other: Laboratory Biomarker Analysis; Other: Placebo

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Arm I (atezolizumab, bevacizumab, capecitabine)

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501

Arm I (atezolizumab, bevacizumab, capecitabine); Arm II (placebo, bevacizumab, capecitabine)

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Arm I (atezolizumab, bevacizumab, capecitabine); Arm II (placebo, bevacizumab, capecitabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (atezolizumab, bevacizumab, capecitabine); Arm II (placebo, bevacizumab, capecitabine)

Placebo OTHER

Given IV

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo, bevacizumab, capecitabine)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed colorectal cancer that is either clinically or histologically proven to be metastatic and has progressed on regimens containing a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, bevacizumab and an anti-EGFR antibody (if tumor is RAS wild-type), or where the treatment was not tolerated or contraindicated
• Measurable disease; Note: previously irradiated sites can be included if there is documented disease progression in that site
• Capecitabine and bevacizumab considered appropriate treatment for the patient
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Absolute neutrophil count \>= 1,500/uL (obtained =\< 7 days prior to randomization)
• Platelets \>= 100,000/uL (obtained =\< 7 days prior to randomization)
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (obtained =\< 7 days prior to randomization); patients with known Gilbert?s syndrome who have serum bilirubin =\< 3 X ULN may enroll
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 1.5 X ULN; \< 3 X ULN if known hepatic metastases (obtained =\< 7 days prior to randomization)
• Hemoglobin \>= 9 g/dL continuation of erythropoietin products is permitted (obtained =\< 7 days prior to randomization); hemoglobin must be stable \>= 9 g/dL \>= 14 days without blood transfusion to maintain hemoglobin level
• Calculated creatinine clearance must be \>= 50 ml/min using the Cockcroft-Gault formula or a 24 hour urine (obtained =\< 7 days prior to randomization)
• The following laboratory values obtained =\< 14 days prior to randomization
• Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR) =\< 1.5 X ULN if not anticoagulated; within local institutional guidelines per local physician if anticoagulated
• Negative pregnancy test done =\< 7 days prior to randomization, for women of childbearing potential only
• Provide informed written consent
• Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)

You may not qualify if:

• Any of the following:
• Pregnant women
• Nursing women
• Women of child-bearing potential must agree to use two forms of adequate contraception from time of initial consent, for the duration of study participation, and for \>= 6 months after the last dose of study drug; medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD); contraceptive measures such as Plan B, sold for emergency use after unprotected sex, are not acceptable methods for routine use; postmenopausal woman must have been amenorrheic for at least 2 years to be considered of non-childbearing potential; sexually active men must use at least one form of adequate contraception from time of initial consent, for the duration of study participation, and for \>= 6 months after the last dose of study drug
• Chemotherapy, biologic anti-cancer therapy, or central field radiation therapy =\< 28 days prior to randomization; Note: local or stereotactic radiation =\< 14 days prior to randomization
• Any investigational agent =\< 28 days or 5 half-lives prior to randomization (whichever is longer)
• Prior treatment with atezolizumab or another PD-L1/PD-1 therapy
• History of allergic reactions attributed to therapeutic antibodies; Note: patients with reactions to chimeric antibodies may be permitted on a case by case basis with approval by study chair by contacting the data manager
• Known untreated central nervous system (CNS) metastases; Note: patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for this purpose =\< 30 days prior to randomization
• Inadequately controlled hypertension (defined as average systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• History of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) grade II or greater congestive heart failure
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery =\< 12 months prior to randomization
• Active coronary heart disease evidenced as angina or requiring medications to prevent angina
• History of stroke or transient ischemic attack, or other arterial thrombosis =\< 12 months prior to randomization

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Related Publications (1)

• Mettu NB, Ou FS, Zemla TJ, Halfdanarson TR, Lenz HJ, Breakstone RA, Boland PM, Crysler OV, Wu C, Nixon AB, Bolch E, Niedzwiecki D, Elsing A, Hurwitz HI, Fakih MG, Bekaii-Saab T. Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2022 Feb 1;5(2):e2149040. doi: 10.1001/jamanetworkopen.2021.49040.

  PMID: 35179586 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

atezolizumab; Bevacizumab; Immunoglobulin G; Disulfides; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Niharika Bansal Mettu, M.D.
• Organization: Duke University Medical Center

niharika.mettu@duke.edu

919-681-2954

Study Officials

• Niharika Mettu

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2016
• First Posted: August 19, 2016
• Study Start: July 7, 2017
• Primary Completion: March 6, 2023
• Study Completion: December 1, 2023
• Last Updated: August 23, 2024
• Results First Posted: February 5, 2020

Record last verified: 2024-07

Locations

US (10)