Testing the Addition of M3814 (Peposertib) to Radiation Therapy for Patients With Advanced Head and Neck Cancer Who Cannot Take Cisplatin

Running, not enrolling · Phase 1

Conditions studied: Advanced Head and Neck Squamous Cell Carcinoma, Advanced Hypopharyngeal Squamous Cell Carcinoma, Advanced Laryngeal Squamous Cell Carcinoma, Advanced Oral Cavity Squamous Cell Carcinoma, Advanced Oropharyngeal Squamous Cell Carcinoma, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVA Hypopharyngeal Carcinoma AJCC v8, Stage IVA Laryngeal Cancer AJCC v8, Stage IVA Lip and Oral Cavity Cancer AJCC v8, Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVB Hypopharyngeal Carcinoma AJCC v8, Stage IVB Laryngeal Cancer AJCC v8, Stage IVB Lip and Oral Cavity Cancer AJCC v8, Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8

In brief

This phase I trial investigates the side effects and best dose of peposertib when given together with radiation therapy in treating patients with head and neck cancer that has spread to other places in the body (advanced) who cannot take cisplatin. Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. This trial aims to see whether adding peposertib to radiation therapy is safe and works well in treating patients with head and neck cancer.

Key facts

Study ID

NCT04533750

Run by

National Cancer Institute (NCI)

People needed

21

Starts

2021-12-20

Expected to finish

2026-12-15

Last updated by the study team

2026-06-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Pathologically (histologically) proven diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx prior to registration;
• Patients with oropharynx cancer need p16 determination by immunohistochemistry (where positive is defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), Note: Institutions must screen patients using a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. A rigorous laboratory accreditation process similar to the United States (U.S.) CLIA certification, such as the provincial accreditation status offered by the Ontario Laboratory Accreditation (OLA) Program in Canada, the College of American Pathologists (CAP), or an equivalent accreditation in other countries, is acceptable. The p16 results must be reported on the pathology report being submitted;
• Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer must be stages T1-2N2-3 or T3N1-3 or T4N0-3 (American Joint Committee on Cancer [AJCC] version 8);
• p16-positive oropharynx cancer patients, stages T4N0-3 or T1-3N2-3 (AJCC version 8);
• The patient has measurable disease as defined by the presence of at least one measurable lesion per RECIST 1.1;
• Please note: A histological or pathological specimen from cervical lymph nodes with well-defined primary site documented clinically or radiologically is acceptable
• Clinical stage noted above should be based upon following diagnostic workup:
• History/physical examination within 30 days prior to registration;
• Examination by radiation oncologist or medical oncologist or otolaryngology (ENT) or head \& neck surgeon 30 days prior to registration, including fiber optic exam with laryngopharyngoscopy;
• Diagnostic quality computed tomography (CT) or magnetic resonance imaging (MRI) of neck, with contrast, within 30 days prior to registration. Fludeoxyglucose F-18 (18F-FDG) whole body positron emission tomography (PET)-CT scan within 42 days of registration is strongly recommended but does not replace the CT or MRI study. Note: If CT component of the PET/CT is of diagnostic quality then PET/CT can be used for eligibility, however the PET/CT scan must be done within 30 days prior to registration
• Diagnostic quality, cross sectional imaging of the thorax within 42 days prior to registration; 18-F-FDG-PET/CT or conventional CT are acceptable
• Age >= 18 years
• Patients must have a contraindication to cisplatin as defined in the following bullet points. Sites must complete the online tool at comogram.org prior to registration to determine if the patient is eligible. The scores must be recorded on a case report form (CRF). (Refer to data submission table on the NRG-HN008 protocol page on the NRG website);
• Age >= 70 with moderate to severe comorbidity, defined as having one or more of the following conditions within 30 days prior to registration;
• Modified Charlson Comorbidity Index >= 1
• Adult Comorbidity Evaluation (ACE)-27 Index >= 1
• Omega score < 0.80
• G-8 score =< 14
• Cancer and Aging Research Group (CARG) Toxicity Score >= 30%
• Cumulative Illness Rating Scale for Geriatrics (CIRS-G) Score >= 4 OR
• Age < 70 with severe comorbidity, defined as having two or more of the following conditions within 30 days prior to registration;
• Modified Charlson Comorbidity Index >= 1
• ACE-27 Index >= 1
• Omega score < 0.80
• G-8 score =< 14

You may not qualify if…

• Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease
• Carcinoma of the neck of unknown primary site origin
• Patients with oral cavity cancer are excluded from participation if the patient is medically operable and the resection of the primary tumor is considered technically feasible by an oral or head and neck cancer surgical subspecialist
• Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease
• Note: Patients with RECIST, version (v.) 1.1 evaluable remaining cancer either in the neck or primary site remain eligible
• Prior invasive malignancy (except non-melanomatous skin cancer carcinoma, in situ of the breast, oral cavity, or cervix, low or very low-risk prostate cancer) unless disease free for a minimum of 3 years
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if not within =< 3 years
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Severe, active co-morbidity defined as follows:
• History of bone marrow transplant and organ transplant, including allogenic stem cell transplantation;
• Unstable angina requiring hospitalization in the last 6 months;
• New York Heart Association Functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.);
• Myocardial infarction within the last 6 months;
• Persistent grade 3-4 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) electrolyte abnormalities that cannot be reversed despite as indicated by repeat testing;
• Ongoing active infection that is associated with symptoms and/or requires antibiotic therapy at the time of registration (excluding asymptomatic bacteriuria, genital herpes, oral herpes, thrush, bacterial vaginosis, vaginal candidiasis, topical antifungals)
• Pregnancy and nursing females, if applicable
• Concomitant use of proton pump inhibitors (or unable to stop 5 days prior to treatment)
• Receipt of live vaccinations within 28 days prior to registration
• Patients unable to discontinue medications or substances that are:
• Strong inhibitors, inducers or sensitive substrates of CYP3A4/5, CYP2C19, or CYP2C9 prior to study treatment;
• Substrates of CYP1A2, CYP2B6, or CYP3A4/5 with a narrow therapeutic prior to study treatment;
• Note: Opioids are allowed, with the exception of methadone
• Fridericia's correction formula (QTcF) > 450 ms for males and > 470 ms for females

Where it is running

• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States
• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States
• Banner University Medical Center - Tucson — Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States
• UC San Diego Moores Cancer Center — La Jolla, California, United States
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Emory University Hospital Midtown — Atlanta, Georgia, United States
• Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States
• Carle at The Riverfront — Danville, Illinois, United States
• Carle Physician Group-Effingham — Effingham, Illinois, United States
• Carle Physician Group-Mattoon/Charleston — Mattoon, Illinois, United States
• Carle Cancer Center — Urbana, Illinois, United States
• The James Graham Brown Cancer Center at University of Louisville — Louisville, Kentucky, United States
• NYU Langone Hospital - Long Island — Mineola, New York, United States
• Laura and Isaac Perlmutter Cancer Center at NYU Langone — New York, New York, United States
• Highland Hospital — Rochester, New York, United States
• University of Rochester — Rochester, New York, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
• Providence Portland Medical Center — Portland, Oregon, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• Sanford Cancer Center Oncology Clinic — Sioux Falls, South Dakota, United States
• Sanford USD Medical Center - Sioux Falls — Sioux Falls, South Dakota, United States

Full record on ClinicalTrials.gov

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