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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)

NCT04533750•National Cancer Institute (NCI)

View on ClinicalTrials.gov

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.

Detailed Description

PRIMARY OBJECTIVE: I. To determine the recommended phase 2 dose (RP2D) of M3814 (peposertib) when given in combination with intensity-modulated radiation therapy (IMRT). SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of the combination of M3814 (peposertib) with radiotherapy. II. To estimate the rates of grade 3 or greater acute toxicities of the regimen. III. To estimate late toxicities of the regimen. IV. To evaluate the clinical response rate, based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, at 3 months post completion of radiotherapy. V. To estimate 6 and 12-month progression-free survival (PFS) in the dose expansion cohort (DEC). VI. To estimate 6 and 12-month overall survival (OS) in the DEC. EXPLORATORY OBJECTIVE: I. To estimate the pharmacokinetic (PK) parameter of M3814 (peposertib) using population PK approaches. OUTLINE: This is a dose-escalation study of peposertib. Beginning 60-90 minutes before each radiation treatment, patients receive peposertib orally (PO) once daily (QD) and undergo IMRT daily Monday-Friday for 7 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), or receive fludeoxyglucose F-18 (18F-FDG) intravenously (IV) and undergo positron emission tomography (PET)/CT during screening and follow-up. After completion of treatment, patients are followed up every 3 months for 2 years.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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
+37 more criteria

Exclusion Criteria

•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;
+13 more criteria

Locations (27)

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

Key Dates

Start Date

December 20, 2021

Primary Completion Date

December 7, 2025

Completion Date

December 15, 2026

Last Updated

March 20, 2026

Enrollment

ACTUAL participants

Conditions

Advanced Head and Neck Squamous Cell CarcinomaAdvanced Hypopharyngeal Squamous Cell CarcinomaAdvanced Laryngeal Squamous Cell CarcinomaAdvanced Oral Cavity Squamous Cell CarcinomaAdvanced Oropharyngeal Squamous Cell CarcinomaClinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Stage III Hypopharyngeal Carcinoma AJCC v8Stage III Laryngeal Cancer AJCC v8Stage III Lip and Oral Cavity Cancer AJCC v8Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8Stage IVA Hypopharyngeal Carcinoma AJCC v8Stage IVA Laryngeal Cancer AJCC v8Stage IVA Lip and Oral Cavity Cancer AJCC v8Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8Stage IVB Hypopharyngeal Carcinoma AJCC v8Stage IVB Laryngeal Cancer AJCC v8Stage IVB Lip and Oral Cavity Cancer AJCC v8Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Interventions

Computed Tomography

PROCEDURE

Fludeoxyglucose F-18

OTHER

Intensity-Modulated Radiation Therapy

RADIATION

Magnetic Resonance Imaging

PROCEDURE

Peposertib

DRUG

Positron Emission Tomography

PROCEDURE

IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

NCT05039801

Advanced Endometrial CarcinomaAdvanced Head and Neck Squamous Cell Carcinoma+36 more

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RECRUITINGPHASE2

Low-Dose Radiotherapy and Anti-PD-1 Immunotherapy as Neoadjuvant Treatment for Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT07371234

Locally Advanced Head and Neck Squamous Cell Carcinoma

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 20, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

Low-Dose Radiotherapy and Anti-PD-1 Immunotherapy as Neoadjuvant Treatment for Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study

Clinical Trial Comparing Induction Treatment With EGFR-ADC MRG003 Alone or in Combination With the Anti PD1 Pucotenlimab, Followed by Radiochemotherapy in Locally Advanced Squamous Cell Cancers of the Head and Neck

Group-Mediated Cognitive Behavioral Resistance Exercise Intervention in Head and Neck Cancer Patients Undergoing Chemoradiation Treatment

Sodium Thiosulfate in Preventing Ototoxicity for Squamous Cell Cancer Patients Undergoing Chemoradiation With Cisplatin