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Head and Neck Carcinoma of Unknown PrimaryPhase 1NCT02567422

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

A Phase 1 study testing Berzosertib, Cisplatin and Computed Tomography in people with Head and Neck Carcinoma of Unknown Primary and Head and Neck Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 19 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Berzosertib, Cisplatin and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
19 sitesUnited States
Study dates
17 Apr 2017to 14 May 2027
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Women of childbearing potential who are sexually active should be willing and able to use medically acceptable forms of contraception throughout the treatment phase of the trial and for up to 6 months following the last administration of study treatment; men who are sexually active must be willing and able to use medically acceptable forms of contraception throughout the treatment phase of the trial and for 6 months after completion of M6620 (VX-970, berzosertib) administration

Who cannot join

  • 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
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  • 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
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because M6620 (VX-970, berzosertib) as a DNA-damage response (DDR) inhibitor may have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620 (VX-970, berzosertib), breastfeeding should be discontinued if the mother is treated with M6620 (VX-970, berzosertib); these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients with well-controlled disease, as determined by CD4 count and viral load, who are on antiretroviral therapy that does not contain a strong inducer or inhibitor of CYP3A4 are allowed on trial; HIV-positive patients on combination antiretroviral therapy with strong inducers or inhibitors of CYP3A4 are ineligible because of the potential for pharmacokinetic interactions; patients with poorly controlled HIV are not eligible due to the increased risk of lethal infections when treated with marrow-suppressive therapy
  • Definitive clinical or radiographic evidence of distant metastasis or adenopathy below the clavicles
  • M6620 (VX-970, berzosertib) is primarily metabolized by CYP3A4; therefore, concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

Other trials in United States

About this study

Official title: 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)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Berzosertib, Cisplatin, Computed Tomography, Laboratory Biomarker Analysis, Magnetic Resonance Imaging
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BerzosertibDrug

    Also called 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970

    Given IV

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo radiation therapy

Study groups in NCT02567422
Study groupRoleWhat they receive
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.
Receives: Drug: Berzosertib; Drug: Cisplatin; Procedure: Computed Tomography; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 6.5 years

  2. 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.

    Measured: Up to 3 weeks after completion of radiation therapy

  3. Establish the Recommended Phase 2 Dose (RP2D)

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

    Measured: Up to 7 weeks

Secondary outcomes (5)

  1. Pharmacokinetic Characteristics of Berzosertib

    The maximum concentration ratio between Day -7 collections to Day 2 collections. Collection time points are baseline, 30 and 55 minutes after the start of M6620 infusion, 5, 15, 30 minutes, 1, 2, 4, 23 (Day 3), 48 (Day 4), and 72 hours (Day 5) after the end of M6620 infusion given on Day 2.

    Measured: Up to Day 5

  2. Potential Drug-drug Interaction

    The maximum concentration of M6620 in the blood when aprepitant is also given.

    Measured: Up to Day 5

  3. Number of Participants Experiencing a Response

    Evaluated by Response Evaluation Criteria in Solid Tumors 1.1. Response is defined as complete response (disappearance of all target and non-target lesions) or partial response (at least a 30% decrease in the sum of diameters of target lesions from baseline).

    Measured: Up to 6.5 years

  4. Number of Participants Experiencing a Metabolic Response

    Assessed by fluorodeoxyglucose-positron emission tomography (FDG PET) and measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Metabolic response are participants demonstrating a complete response (disappearance of all target and non-target lesions) or a partial response (at least a 30% decrease in the sum of diameters of target lesions from baseline).

    Measured: At week 12 after completing intervention

  5. Expression of Tissue-based Biomarkers as Markers of Deoxyribonucleic Acid Damage and Predictors of Clinical Outcome

    Kaplan-Meier curves for Progression Free Survival (PFS), defined as time to disease progression, and Overall Survival (OS), defined as time until death or off study, were used to evaluate if the gene expression profiles of ERCC1 and XRCC1, and TP53 correlated to these outcomes.

    Measured: Up to 6.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2015 (estimated)
  2. Study start17 Apr 2017
  3. Primary completion31 Dec 2023
  4. Study completion14 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02567422
Sponsor's protocol ID
NCI-2015-01643
Other IDs
NCI-2015-01643, 9950, 9950, N01CM00100, UM1CA186690, UM1CA186691
Status last verified
May 2026
First submitted
2 Oct 2015
Last updated
31 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Berzosertib, Cisplatin and Computed Tomography in people with Head and Neck Carcinoma of Unknown Primary and Head and Neck Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Grade 3, 4, and 5 Adverse Events (time frame: Up to 6.5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02567422.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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