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M6620, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT02567422
Recruitment Status : Recruiting
First Posted : October 5, 2015
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase I trial studies the side effects and best dose of ATR kinase inhibitor M6620 (M6620) when given together with cisplatin and radiation therapy in treating patients with human papillomavirus negative (HPV) (-) head and neck squamous cell carcinoma that has spread from where it started to nearby tissue or lymph nodes. ATR kinase inhibitor M6620 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, 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 ATR kinase inhibitor M6620 together with cisplatin and radiation therapy may work better in treating patients with locally advanced HPV-negative head and neck squamous cell carcinoma.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Human Papillomavirus Negative Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7 Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7 Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7 Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7 Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7 Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7 Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7 Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7 Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7 Drug: ATR Kinase Inhibitor M6620 Drug: Cisplatin Other: Laboratory Biomarker Analysis Other: Pharmacological Study Radiation: Radiation Therapy Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the safety and tolerability of M6620 (VX-970) when administered along with weekly cisplatin and radiation therapy (XRT) in patients with locoregionally advanced HPV (-) 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). II. Assess for potential drug-drug interaction between M6620 (VX-970) 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 ATR kinase inhibitor M6620.

Patients receive ATR kinase inhibitor M6620 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of M6620 (VX-970) in Combination With Cisplatin and XRT in Patients With Locally Advanced HPV (-) Head and Neck Squamous Cell Carcinoma (HNSCC; SDC 10060121)
Actual Study Start Date : September 2, 2016
Estimated Primary Completion Date : August 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Cisplatin

Arm Intervention/treatment
Experimental: Treatment (M6620, cisplatin, radiation therapy)
Patients receive ATR kinase inhibitor M6620 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.
Drug: ATR Kinase Inhibitor M6620
Given IV
Other Names:
  • M 6620
  • M6620
  • VX-970

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation




Primary Outcome Measures :
  1. Frequency and grade of toxicity [ Time Frame: Up to 2 years ]
    According to the Cancer Therapy Evaluation Program National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v. 5).

  2. Incidence of dose limiting toxicities [ Time Frame: Up to completion of radiation therapy ]
    Graded according to NCI CTCAE v. 5.

  3. Recommended phase 2 dose [ Time Frame: Up to 7 weeks ]
    Defined as the highest doses of cisplatin and ATR kinase inhibitor M6620 safely combined with radiation.


Secondary Outcome Measures :
  1. Pharmacokinetic characteristics of ATR kinase inhibitor M6620 [ 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 ]
    Calculating maximum concentration, area under the curve, clearance, half life, and steady state volume using Wilcoxon (non-parametric) test.

  2. 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 ]
    Evaluated by Response Evaluation Criteria in Solid Tumors 1.1.

  3. Metabolic response rate by fluorodeoxyglucose-positron emission tomography (PET) [ Time Frame: Up to 2 years ]
    Measured by PET Response Criteria in Solid Tumors.


Other Outcome Measures:
  1. Expression of tissue-based biomarkers as markers of deoxyribonucleic acid damage and predictors of clinical outcome [ Time Frame: Baseline ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 that is not amenable to surgical resection
  • Patients with primary oropharynx HNSCC must be HPV (-) according to local institutional definition using either p16 immunohistochemistry or HPV testing
  • Carcinoma of the neck of unknown primary site origin (regardless of HPV/p16 status) is eligible
  • 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
  • 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 6 months after completion of M6620 (VX-970) 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) 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970) 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; breastfeeding should be discontinued if the mother is treated with M6620 (VX-970)
  • 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; patients with poorly controlled HIV are not eligible
  • Definitive clinical or radiographic evidence of distant metastasis or adenopathy below the clavicles
  • Concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02567422


Locations
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Site Public Contact    800-826-4673    becomingapatient@coh.org   
Principal Investigator: Erminia Massarelli         
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Site Public Contact    916-734-3089      
Principal Investigator: Jonathan W. Riess         
United States, Connecticut
Smilow Cancer Center/Yale-New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Site Public Contact    203-785-5702    canceranswers@yale.edu   
Principal Investigator: Barbara A. Burtness         
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Site Public Contact    203-785-5702    canceranswers@yale.edu   
Principal Investigator: Barbara A. Burtness         
United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Site Public Contact    888-946-7447      
Principal Investigator: Conor E. Steuer         
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Site Public Contact    404-778-1868      
Principal Investigator: Conor E. Steuer         
United States, Kentucky
University of Kentucky/Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Contact: Site Public Contact    859-257-3379      
Principal Investigator: Susanne M. Arnold         
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Suspended
Baltimore, Maryland, United States, 21287
United States, Ohio
Case Western Reserve University Suspended
Cleveland, Ohio, United States, 44106
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Site Public Contact    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: Darrion L. Mitchell         
United States, Virginia
University of Virginia Cancer Center Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Site Public Contact    434-243-6303    PAS9E@virginia.edu   
Principal Investigator: Varinder Kaur         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Site Public Contact    800-622-8922      
Principal Investigator: Justine Yang-Bruce         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Taofeek Owonikoko JHU Sidney Kimmel Comprehensive Cancer Center LAO

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02567422     History of Changes
Other Study ID Numbers: NCI-2015-01643
NCI-2015-01643 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9950 ( Other Identifier: JHU Sidney Kimmel Comprehensive Cancer Center LAO )
9950 ( Other Identifier: CTEP )
N01CM00100 ( U.S. NIH Grant/Contract )
UM1CA186690 ( U.S. NIH Grant/Contract )
UM1CA186691 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2015    Key Record Dates
Last Update Posted: October 10, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cisplatin
Antineoplastic Agents