Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Oral Squamous Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Patients receive berzosertib IV over 60 minutes on day -7 and then weekly on day 2 and cisplatin IV over 30-60 minutes weekly on day 1. Patients also undergo radiation therapy once daily, 5 days a week. Treatment continues for up to 7 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT, PET/CT, or MRI throughout the study.

Berzosertib

Computed Tomography

Laboratory Biomarker Analysis

Magnetic Resonance Imaging

Positron Emission Tomography

Radiation Therapy

Taofeek K Owonikoko

This phase I trial studies the side effects and best dose of berzosertib (M6620) when given together with cisplatin and radiation therapy in treating patients with head and neck squamous cell carcinoma that has spread from where it started to nearby tissue or lymph nodes (locally advanced). M6620 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving M6620 together with cisplatin and radiation therapy may work better in treating patients with locally advanced head and neck squamous cell carcinoma.

PRIMARY OBJECTIVES:

I. Assess the safety and tolerability of M6620 (VX-970, berzosertib) when administered along with weekly cisplatin and radiation therapy (XRT) in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC).

II. Establish the recommended phase 2 dose (RP2D) of the combination.

SECONDARY OBJECTIVES:

I. Characterize the pharmacokinetic (PK) profile of M6620 (VX-970, berzosertib).

II. Assess for potential drug-drug interaction between M6620 (VX-970, berzosertib) and aprepitant.

III. To observe and record anti-tumor activity. IV. To assess the rate of complete metabolic response (CMR) at 12 weeks post completion of chemoradiation using 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans.

V. To collect archival tumor material for retrospective analysis of association between tissue-based biomarkers and clinical outcome.

OUTLINE: This is a dose-escalation study of berzosertib.

Patients receive berzosertib intravenously (IV) over 60 minutes on day -7 and then weekly on day 2 and cisplatin IV over 30-60 minutes weekly on day 1. Patients also undergo radiation therapy once daily, 5 days a week. Treatment continues for up to 7 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT), PET/CT, or magnetic resonance imaging (MRI) throughout the study.

After completion of study treatment, patients are followed up for 30 days, every 2 weeks for 3 months, and then every 3 months for 2 years.

Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer

A Phase I Study of M6620 (VX-970, Berzosertib) in Combination With Cisplatin and XRT in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC; SDC 10060121)

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.

According to the Cancer Therapy Evaluation Program National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v. 5).

Defined as the highest doses of cisplatin and berzosertib safely combined with radiation.

Calculating maximum concentration, area under the curve, clearance, half-life, and steady state volume using Wilcoxon (non-parametric) test.

Evaluated by Response Evaluation Criteria in Solid Tumors 1.1.

Measured by PET Response Criteria in Solid Tumors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer	NCT02567422	Head and Neck C... Head and Neck S... Stage III Hypop... Stage III Laryn... Stage III Oral ... Stage III Oroph... Stage III Sinon... Stage IV Hypoph... Stage IV Laryng... Stage IV Oral C... Stage IV Oropha... Stage IV Sinona...	Berzosertib Cisplatin Computed Tomogr... Laboratory Biom... Magnetic Resona... Positron Emissi... Radiation Thera...	18 Years -	National Cancer Institute (NCI)
Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer	NCT02567422	Head and Neck C... Head and Neck S... Stage III Hypop... Stage III Laryn... Stage III Oral ... Stage III Oroph... Stage III Sinon... Stage IV Hypoph... Stage IV Laryng... Stage IV Oral C... Stage IV Oropha... Stage IV Sinona...	Berzosertib Cisplatin Computed Tomogr... Laboratory Biom... Magnetic Resona... Positron Emissi... Radiation Thera...	18 Years -	National Cancer Institute (NCI)
Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer	NCT02567422	Head and Neck C... Head and Neck S... Stage III Hypop... Stage III Laryn... Stage III Oral ... Stage III Oroph... Stage III Sinon... Stage IV Hypoph... Stage IV Laryng... Stage IV Oral C... Stage IV Oropha... Stage IV Sinona...	Berzosertib Cisplatin Computed Tomogr... Laboratory Biom... Magnetic Resona... Positron Emissi... Radiation Thera...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iii sinonasal squamous cell carcinoma ajcc v6 and v7