NCI/CTEP 10276: A Phase 1/2 Study of M3814 and Avelumab in Combination with Hypofractionated Radiation in Patients with Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies

Study Name
	NCI/CTEP 10276: A Phase 1/2 Study of M3814 and Avelumab in Combination with Hypofractionated Radiation in Patients with Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies
ClinicalTrials.gov Identifier (if applicable)
	NCT04068194
Clinical Trial Category (check all that apply)
	Beyond First Line Therapy Immunotherapy Radiation Therapy Other Novel Therapy
Study Center
Institution Name
	NYU Perlmutter Cancer Center
Institution Address
	160 E 34th St
City
	New York
State
	New York
Zip Code
	10276
Country
	United States
Website
	https://clinicaltrials.med.nyu.edu/clinicaltrial/1346/phase-iii-study-m3814/
List additional Institutions (include address, phone number, and website)
	Entire NCTN, currently: UC Irvine Health/Chao Family Comprehensive Cancer Center Contact: 877-827-8839 ucstudy@uci.edu Principal Investigator: Farshid Dayyani Northwestern University Contact: 312-695-1301 cancer@northwestern.edu Principal Investigator: Aparna Kalyan Rutgers Cancer Institute of New Jersey Contact: 732-235-7356 Principal Investigator: Salma K. Jabbour NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center Contact: 212-305-6361 nr2616@cumc.columbia.edu Principal Investigator: Susan E. Bates NYP/Weill Cornell Medical Center Contact: 212-746-1848 Principal Investigator: Elizabeta C. Popa Virginia Commonwealth University/Massey Cancer Center Contact: CTOclinops@vcu.edu Principal Investigator: Jennifer L. Myers
Study Contacts
Principal Investigator
	Kristen Spencer, DO, MPH
P.I. Phone
	(212) 731-6667
P.I. Email
	kristen.spencer@nyulangone.org
List additional Principal Investigators (include phone number and email)
	See above (additional institutions)
Study Coordinator
	Monica Dureja
Study Coordinator Phone
	(212) 263-4415
Study Coordinator Email
	Monica.Dureja@nyulangone.org
OVERVIEW – in layman’s terms (150 words max)
	The phase II portion of this trial studies how well peposertib (a drug that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth) works with avelumab and hypofractionated radiation therapy in treating patients with hepatobiliary malignancies that have spread to other places in the body (advanced/metastatic).
Enrollment
	62
Study Start Date
	04/07/2020
Estimated Completion Date
	12/03/2024
Purpose of the Study – in Layman’s Terms (use the “+” to add more list items)
	To determine the efficacy of the combination of hypofractionated radiation, M3814, and avelumab as compared to the combination of hypofractionated radiation and avelumab in patients with advanced/metastatic hepatobiliary tumors by response rate. To observe and record anti-tumor activity by measurement of disease control rate (DCR), duration of response (DOR), progression free survival (PFS), and overall survival (OS). To determine if baseline deoxyribonucleic acid (DNA) repair defects inherent to some cholangiocarcinomas correlate with a more dramatic response to radiation.
Inclusion Criteria – Patients Must:
	have a histologically confirmed metastatic or locally advanced unresectable cholangiocarcinoma/gallbladder carcinoma have progressed on at least 1 prior standard of care therapy have an (ECOG) performance status =< 2 have 1 tumor to irradiate and at least 1 RECIST measurable lesion that will not be irradiated be willing to undergo fresh biopsies at baseline have the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption
Exclusion Criteria – Patients Must NOT:
	have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents other than as part of a gemcitabine-based regimen have an active autoimmune disease requiring systemic corticosteroids greater than the equivalent of prednisone 10 mg daily
REQUIRED TESTS PRIOR TO BEGINNING STUDY TREATMENT – in layman’s terms
	Potentially repeat tumor imaging (e.g. CT scan, PET scan) Potentially a fresh tumor biopsy Blood work EKG
POTENTIAL SIDE-EFFECTS – in layman’s terms
	Lowered blood counts, electrolyte abnormalities, nausea/vomiting, rash, lung inflammation, colon inflammation
Financial Assistance is available to participants for travel, lodging, etc.
	No