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

• Register: ClinicalTrials.gov
• Last refreshed on: 25 March 2024
• Main ID: NCT02567422
• Date of registration: 02/10/2015
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer
• Scientific 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)
• Date of first enrolment: April 17, 2017
• Target sample size: 43
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02567422
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Taofeek K Owonikoko
• Affiliation: University of Pittsburgh Cancer Institute LAO

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- 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

Exclusion Criteria:

- 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

- 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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7

Stage III Sinonasal Squamous Cell Carcinoma AJCC v6 and v7

Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7

Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7

Stage IVC Sinonasal Squamous Cell Carcinoma AJCC v7

Head and Neck Carcinoma of Unknown Primary

Head and Neck Squamous Cell Carcinoma

Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7

Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7

Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7

Stage IVB Sinonasal Squamous Cell Carcinoma AJCC v7

Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7

Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7

Stage IV Sinonasal Squamous Cell Carcinoma AJCC v7

Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7

Stage IVA Sinonasal Squamous Cell Carcinoma AJCC v7

Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7

Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7

Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Intervention(s)

Drug: Cisplatin

Other: Laboratory Biomarker Analysis

Drug: Berzosertib

Radiation: Radiation Therapy

Primary Outcome(s)

Recommended phase 2 dose [Time Frame: Up to 7 weeks]

Incidence of dose limiting toxicities [Time Frame: Up to completion of radiation therapy]

Frequency and grade of toxicity [Time Frame: Up to 2 years]

Secondary Outcome(s)

Overall response rate defined as complete response (CR) + partial response (PR) [Time Frame: From the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years]

Metabolic response rate by fluorodeoxyglucose-positron emission tomography (PET) [Time Frame: Up to 2 years]

Pharmacokinetic characteristics of berzosertib [Time Frame: At baseline, 30 and 55 minutes after start of infusion, 5, 15, and 30 minutes and 1, 2, 4, 23, 48, and 72 hours after end of infusion]

Secondary ID(s)

N01CM00100

UM1CA186690

UM1CA186691

NCI-2015-01643

9950

Source(s) of Monetary Support

Please refer to primary and secondary sponsors