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)
5 other identifiers
interventional
43
1 country
19
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2017
Longer than P75 for phase_1
19 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
October 2, 2015
CompletedFirst Posted
Study publicly available on registry
October 5, 2015
CompletedStudy Start
First participant enrolled
April 17, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2023
CompletedResults Posted
Study results publicly available
June 27, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 14, 2026
ExpectedDecember 4, 2025
November 1, 2025
6.7 years
October 2, 2015
November 4, 2024
November 15, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Participants Experiencing Grade 3, 4, and 5 Adverse Events
According to the Cancer Therapy Evaluation Program National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v. 5). The highest grade experienced by the participant will be reported.
Up to 6.5 years
Number of Participants Experiencing a Dose Limiting Toxicities
Dose limiting toxicities are protocol-specific adverse events considered at least possibly related to the study intervention. Graded according to NCI CTCAE v5.
Up to 3 weeks after completion of radiation therapy
Establish the Recommended Phase 2 Dose (RP2D)
Defined as the highest doses of cisplatin and berzosertib safely combined with radiation.
Up to 7 weeks
Secondary Outcomes (5)
Pharmacokinetic Characteristics of Berzosertib
Up to Day 5
Potential Drug-drug Interaction
Up to Day 5
Number of Participants Experiencing a Response
Up to 6.5 years
Number of Participants Experiencing a Metabolic Response
At week 12 after completing intervention
Expression of Tissue-based Biomarkers as Markers of Deoxyribonucleic Acid Damage and Predictors of Clinical Outcome
Up to 6.5 years
Study Arms (1)
Treatment (berzosertib, cisplatin, radiation therapy)
EXPERIMENTALPatients 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.
Interventions
Undergo MRI
Undergo PET/CT
Undergo radiation therapy
Given IV
Given IV
Undergo CT or PET/CT
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed head and neck squamous cell cancer (HNSCC) including paranasal sinus cancers but excluding nasopharyngeal carcinomas
- Clinical staged III or IV HNSCC, according to American Joint Committee on Cancer (AJCC) 7th Edition, that is not amenable to surgical resection
- Carcinoma of the neck of unknown primary site origin (regardless of HPV/p16 status) is eligible
- Age \>= 18 years; because no dosing or adverse event data are currently available on the use of M6620 (VX-970, berzosertib) in combination with cisplatin in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 3 months
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 10 mm (\>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- The effects of M6620 (VX-970, berzosertib) on the developing human fetus are unknown; for this reason and because DNA-damage response (DDR) inhibitors as well as other therapeutic agents used in this trial may have teratogenic potential, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion of M6620 (VX-970, berzosertib) administration
- Ability to understand and the willingness to sign a written informed consent document
- +1 more criteria
You may not qualify if:
- Patients with nasopharyngeal carcinoma, skin squamous cell carcinoma (SCC), and salivary gland carcinomas are not eligible
- Patients who are receiving adjuvant chemoradiation after surgical resection of the primary site of disease
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- Patients on tacrolimus or any other immunosuppressants with significant interaction with cisplatin
- Patient who requires live vaccine administration
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970, berzosertib) or cisplatin
- Prior systemic chemotherapy for the current cancer (prior chemotherapy for a different cancer is allowed)
- Prior receipt of radiotherapy that would result in overlap of the new and old radiation therapy fields
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring intravenous antibiotics at the time of treatment initiation
- Symptomatic congestive heart failure (requiring hospital stay within the last 6 months)
- Myocardial infarction within the last 6 months
- Unstable angina pectoris, cardiac arrhythmia
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Grants Administrative Manager
- Organization
- Johns Hopkins University/SKCCC
Study Officials
- PRINCIPAL INVESTIGATOR
Taofeek K Owonikoko
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
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
October 2, 2015
First Posted
October 5, 2015
Study Start
April 17, 2017
Primary Completion
December 31, 2023
Study Completion (Estimated)
May 14, 2026
Last Updated
December 4, 2025
Results First Posted
June 27, 2025
Record last verified: 2025-11
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.