INTACT: Phase III randomized trial of concurrent chemoradiotherapy with or without atezolizumab in localized muscle invasive bladder cancer—SWOG/NRG1806.

Authors

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Parminder Singh

Mayo Clinic Arizona, Phoenix, AZ

Parminder Singh , Cathy Tangen , Jason A. Efstathiou , Seth P. Lerner , Sameer G. Jhavar , Noah M. Hahn , Brian Addis Costello , Srikala S. Sridhar , Weliang Du , Joshua J. Meeks , Bishoy Morris Faltas , Petros Grivas , Felix Y Feng , Ronald C. Chen , Alicia K. Morgans , Amit Gupta , Richard Carlton Bangs , Kathryn A. Winter , Nicholas J. Vogelzang , Ian Murchie Thompson Jr.

Organizations

Mayo Clinic Arizona, Phoenix, AZ, Fred Hutchinson Cancer Center, Seattle, WA, Massachusetts General Hospital, Boston, MA, Baylor College of Medicine, Houston, TX, Scott and White Hosp Texas A and M Univ, Temple, TX, Johns Hopkins University School of Medicine, Baltimore, MD, Mayo Clinic, Rochester, MN, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, MD Anderson Cancer Center, Houston, TX, Jesse Brown VAMC, Northwestern University, Feinberg School of Medicine, Chicago, IL, Weill Cornell Medicine, New York, NY, University of Washington, Seattle, WA, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, University of Kansas, Kansas City, KS, Northwestern University, Chicago, IL, Univ of Iowa, Iowa City, IA, SWOG, San Antonio, TX, Statistical Center, Radiation Therapy Oncology Group, Philadelphia, PA, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, UT Health Science Center, San Antonio, TX

Research Funding

Other
NIH/NCI grants CA180888, CA180819, CA180868, CA180820, CA180821, CA180863, Pharmaceutical/Biotech Company.

Background: Chemoradiotherapy(CRT) is a SOC for patients with muscle invasive bladder cancer (MIBC) who refuse or are not fit for radical cystectomy. Radiotherapy and chemotherapy are known to increases the PD-L1 expression in bladder cancer. Based on these observations, we hypothesized that addition of atezolizumab to CRT will increase its efficacy. Methods: This is a randomized phase III trial testing CRT with and without atezolizumab for 6 months in 475 patients with MIBC. Pts will be stratified on performance status (0-1 vs. 2); clinical stage (T2 vs T3/T4a, chemotherapy(cisplatin vs 5FU+mitomycin vs gemcitabine); and radiation field (bladder only vs small pelvis). Patients will undergo biopsy 18 week from registration. If they have residual disease they will be taken off protocol treatment and can proceed with alternative SOC option including radical cystectomy. Patients will be followed for 5 years. The primary end point of the study is bladder intact event –free survival (BIEFS). The event is comprised of: recurrence or residual muscle-invasive bladder cancer at 18 weeks or later, clinical evidence of nodal or metastatic disease, radical cystectomy, or death due to any cause. This composite endpoint is reflective of the intent of bladder preservation strategy with radical cystectomy included as one of the outcomes. Secondary end points include overall survival, modified event free survival, pathologic response at 18 weeks, metastasis free survival, cancer specific survival, rate of salvage cystectomy, rate of adverse event and QOL & PRO end points. The expected 3 year BIEFS for the control arm is 52%. The study leadership concluded that a 12% improvement in this endpoint is meaningful for this patient population. With a sample size of 475 patients the study has 85% power to detect the improvement from 52% to 64% in the BIEFS at 3 years (hazard ratio=0.68). The study team will perform translational studies evaluating tumor tissue, whole blood and urine for molecular and immunologic markers of immune response and response to RT. Successful completion of this trial could lead to a new treatment paradigm for patients with muscle invasive bladder cancer. Clinical trial information: NCT03775265

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Abstract Details

Meeting

2020 Genitourinary Cancers Symposium

Session Type

Trials in Progress Poster Session

Session Title

Trials in Progress Poster Session B: Urothelial Carcinoma; Penile, Urethral, Testicular, and Adrenal Cancers

Track

Urothelial Carcinoma,Adrenal Cancer,Penile Cancer,Prostate Cancer - Advanced,Prostate Cancer - Localized,Testicular Cancer,Urethral Cancer

Sub Track

Therapeutics

Clinical Trial Registration Number

NCT03775265

Citation

J Clin Oncol 38, 2020 (suppl 6; abstr TPS586)

Abstract #

TPS586

Poster Bd #

N4

Abstract Disclosures