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

Status
Active
Cancer Type
Head and Neck Cancer
Trial Phase
Phase I
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT02567422
Protocol IDs
9950 (primary)
NCI-2015-01643
Study Sponsor
JHU Sidney Kimmel Comprehensive Cancer Center LAO

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.

Objectives

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.

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.

Eligibility

  1. Patients must have histologically or cytologically confirmed head and neck squamous cell cancer (HNSCC) including paranasal sinus cancers but excluding nasopharyngeal carcinomas
  2. Clinical staged III or IV HNSCC that is not amenable to surgical resection
  3. Carcinoma of the neck of unknown primary site origin (regardless of HPV/p16 status) is eligible
  4. Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  5. Life expectancy of greater than 3 months
  6. 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
  7. Leukocytes >= 3,000/mcL
  8. Absolute neutrophil count >= 1,500/mcL
  9. Platelets >= 100,000/mcL
  10. Total bilirubin within normal institutional limits
  11. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  12. Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  13. 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
  14. Ability to understand and the willingness to sign a written informed consent document
  15. 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

Treatment Sites in Georgia

Emory University Hospital - Midtown


550 Peachtree Street NE
Atlanta, GA 30308
404-686-4411
www.emoryhealthcare.org

Winship Cancer Institute of Emory University


1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

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