Clinical Trials /

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

NCT02567422

Description:

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 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 head and neck squamous cell carcinoma.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Nasal Cavity and Paranasal Sinus Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: M6620, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
  • Official Title: A Phase I Study of M6620 (VX-970) in Combination With Cisplatin and XRT in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC; SDC 10060121)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2015-01643
  • SECONDARY ID: NCI-2015-01643
  • SECONDARY ID: 9950
  • SECONDARY ID: 9950
  • SECONDARY ID: N01CM00100
  • SECONDARY ID: UM1CA186690
  • SECONDARY ID: UM1CA186691
  • NCT ID: NCT02567422

Conditions

  • Head and Neck Squamous Cell Carcinoma
  • 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

Interventions

DrugSynonymsArms
ATR Kinase Inhibitor M6620M 6620, M6620, VX-970Treatment (M6620, cisplatin, radiation therapy)
CisplatinAbiplatin, 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, PlatosinTreatment (M6620, cisplatin, radiation therapy)

Purpose

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 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 head and neck squamous cell carcinoma.

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (M6620, cisplatin, radiation therapy)ExperimentalPatients 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.
  • ATR Kinase Inhibitor M6620
  • Cisplatin

Eligibility 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

          -  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

          -  The effects of M6620 (VX-970) 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) 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
             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) 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) 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), breastfeeding should
             be discontinued if the mother is treated with M6620 (VX-970); 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; patients with poorly controlled HIV are not eligible

          -  Definitive clinical or radiographic evidence of distant metastasis or adenopathy below
             the clavicles

          -  M6620 (VX-970) 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency and grade of toxicity
Time Frame:Up to 2 years
Safety Issue:
Description:According to the Cancer Therapy Evaluation Program National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v. 5).

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Calculating maximum concentration, area under the curve, clearance, half-life, and steady state volume using Wilcoxon (non-parametric) test.
Measure: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
Safety Issue:
Description:Evaluated by Response Evaluation Criteria in Solid Tumors 1.1.
Measure:Metabolic response rate by fluorodeoxyglucose-positron emission tomography (PET)
Time Frame:Up to 2 years
Safety Issue:
Description:Measured by PET Response Criteria in Solid Tumors.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

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