Testing the Addition of M3814 (Peposertib) to Radiation Therapy for Patients With Advanced Head and Neck Cancer Who Cannot Take Cisplatin
Phase I Trial With Expansion Cohort of DNA-PK Inhibition and IMRT in Cisplatin-Ineligible Patients With Stage 3-4 Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
3 other identifiers
interventional
21
1 country
27
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Dec 2021
Longer than P75 for phase_1
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 29, 2020
CompletedFirst Posted
Study publicly available on registry
September 1, 2020
CompletedStudy Start
First participant enrolled
December 20, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 7, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 15, 2026
ExpectedApril 13, 2026
December 1, 2025
4 years
August 29, 2020
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Dose-limiting toxicity
Up to 28 days after the end of intensity-modulated radiation therapy (IMRT)
Secondary Outcomes (5)
Incidence of acute toxicity
Up to 3 months from IMRT completion
Incidence of late toxicity
More than 3 months from IMRT completion for up to 2 years
Clinical response rate
At 3 months post completion of IMRT
Progression-free survival (PFS) rates
At 6 months and 1 year
Overall survival (OS) rates
At 6 months and 1 year
Other Outcomes (1)
Pharmacokinetic (PK) parameter of M3814 (peposertib)
Within 30 minutes before administration, 2 hours and 4 hours after administration on day 1 of weeks 1 and 2
Study Arms (1)
Treatment (peposertib, IMRT)
EXPERIMENTALBeginning 60-90 minutes before each radiation treatment, patients receive peposertib PO QD and undergo IMRT daily Monday-Friday for 7 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, or 18F-FDG PET/CT during screening and follow-up.
Interventions
Given IV
Undergo IMRT
Undergo CT or PET/CT
Undergo MRI
Given PO
Undergo PET/CT
Eligibility Criteria
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
- +32 more criteria
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)
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologycollaborator
- National Cancer Institute (NCI)lead
Study Sites (27)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Highland Hospital
Rochester, New York, 14620, United States
University of Rochester
Rochester, New York, 14642, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Maura L Gillison
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 29, 2020
First Posted
September 1, 2020
Study Start
December 20, 2021
Primary Completion
December 7, 2025
Study Completion (Estimated)
December 15, 2026
Last Updated
April 13, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.