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Beginning 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.

Computed Tomography

Fludeoxyglucose F-18

Intensity-Modulated Radiation Therapy

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Positron Emission Tomography

Site Public Contact

Michael A. Samuels

Ricklie A. Julian

Loren K. Mell

Stuart E. Samuels

Jimmy J. Caudell

Soumon Rudra

Prem Sobti

Rebecca A. Redman

Zujun Li

Yuhchyau Chen

Minh Phan

Nitya Alluri

Daniel Almquist

John F. Deeken

Maura L Gillison

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.

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.

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)

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.

Plasma PK values will be estimated in the context of the Merck popPK model at the end of the trial and reported as such. PK-outcome relationships may be assessed in an exploratory fashion.

Will be as measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0

Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1.

Will be estimated using the Kaplan-Meier (K-M) method (Kaplan and Meier 1958). Point estimates of the PFS at 6 months and 1 year post-IMRT along with their 95% confidence intervals after using a log-log transformation will be calculated using the K-M curves.

Will be estimated using the Kaplan-Meier (K-M) method (Kaplan and Meier 1958). Point estimates of the OS at 6 months and 1 year post-IMRT along with their 95% confidence intervals after using a log-log transformation will be calculated using the K-M curves.

NRG Oncology

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Testing the Addition of M3814 (Peposertib) to Radiation Therapy for Patients With Advanced Head and Neck Cancer Who Cannot Take Cisplatin	NCT04533750	Advanced Head a... Advanced Hypoph... Advanced Laryng... Advanced Oral C... Advanced Oropha... Clinical Stage ... Stage III Hypop... Stage III Laryn... Stage III Lip a... Stage III Oroph... Stage IVA Hypop... Stage IVA Laryn... Stage IVA Lip a... Stage IVA Oroph... Stage IVB Hypop... Stage IVB Laryn... Stage IVB Lip a... Stage IVB Oroph...	Computed Tomogr... Fludeoxyglucose... Intensity-Modul... Magnetic Resona... Peposertib Positron Emissi...	18 Years -	National Cancer Institute (NCI)
Testing the Addition of M3814 (Peposertib) to Radiation Therapy for Patients With Advanced Head and Neck Cancer Who Cannot Take Cisplatin	NCT04533750	Advanced Head a... Advanced Hypoph... Advanced Laryng... Advanced Oral C... Advanced Oropha... Clinical Stage ... Stage III Hypop... Stage III Laryn... Stage III Lip a... Stage III Oroph... Stage IVA Hypop... Stage IVA Laryn... Stage IVA Lip a... Stage IVA Oroph... Stage IVB Hypop... Stage IVB Laryn... Stage IVB Lip a... Stage IVB Oroph...	Computed Tomogr... Fludeoxyglucose... Intensity-Modul... Magnetic Resona... Peposertib Positron Emissi...	18 Years -	National Cancer Institute (NCI)

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