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Phase II Study of Short Course FOLFOX Chemotherapy With Either Nivolumab or Nivolumab + Radiation in the First Line Treatment of Metastatic or Unresectable Gastroesophageal Cancers (BMS Protocol CA209-76L)

NCT04021108

Description:

This is a randomized phase II study examining nivolumab alone versus radiation therapy with nivolumab in subjects who did not have disease progression to initial therapy with the combination of FOLFOX and Nivolumab.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of Short Course FOLFOX Chemotherapy With Either Nivolumab or Nivolumab + Radiation in the First Line Treatment of Metastatic or Unresectable Gastroesophageal Cancers (BMS Protocol CA209-76L)
  • Official Title: Phase II Study of Short Course FOLFOX Chemotherapy With Either Nivolumab or Nivolumab + Radiation in the First Line Treatment of Metastatic or Unresectable Gastroesophageal Cancers (BMS Protocol CA209-76L)

Clinical Trial IDs

  • ORG STUDY ID: 1812019872
  • NCT ID: NCT04021108

Conditions

  • Gastroesophageal Adenocarcinoma

Interventions

DrugSynonymsArms
Nivolumab 240 MGCohort 1

Purpose

This is a randomized phase II study examining nivolumab alone versus radiation therapy with nivolumab in subjects who did not have disease progression to initial therapy with the combination of FOLFOX and Nivolumab.

Detailed Description

      This is a randomized phase II study examining nivolumab alone versus radiation therapy with
      nivolumab in subjects who did not have disease progression to initial therapy with the
      combination of FOLFOX and Nivolumab. Subjects with advanced unresectable or metastatic
      gastroesophageal adenocarcinoma are eligible. All subjects will receive FOLFOX + nivolumab
      therapy. Subjects who demonstrate at least stable disease, as per RECIST 1.1, on their first
      imaging assessment at two months will receive one additional month of FOLFOX + nivolumab (3
      months total), and then will be randomly assigned at a 1:1 ratio to receive either nivolumab
      alone or nivolumab plus radiation therapy. Radiation therapy fields and technique will be
      approved by central review. Radiation will be planned at 4Gy x 5 doses (20 Gy total), given
      concurrently with nivolumab. After 4 months of therapy, patients who remain on study will
      receive nivolumab 480 mg every 4 weeks. Subjects will be on study (intervention + follow-up)
      for approximately 24 months. The projected end date of the study, including data analysis, is
      December 2023
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1OtherSubjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks)
  • Nivolumab 240 MG
Cohort 2ExperimentalSubjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions)
  • Nivolumab 240 MG

Eligibility Criteria

        Inclusion Criteria

          -  Subjects with a diagnosis of advanced unresectable or metastatic gastroesophageal
             adenocarcinoma (eg. gastric, gastroesophageal junction, and esophageal adenocarcinoma)

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Age > 18 years

          -  ECOG performance status ≤ 1

          -  Absolute neutrophil count ≥ 1,500/mL

          -  Platelets ≥ 100,000/mL

          -  Total bilirubin ≤ 1.5x upper limits of normal, unless the patient has known Gilbert's
             disease.

          -  AST/ALT ≤ 2.5 upper limits of normal, or < 5x ULN for subjects with liver metastases

          -  Creatinine ≤ 1.5 mg/dl. If Creatinine > 1.5 mg/dl, creatinine clearance > 60 ml/min

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 28 days prior to
             initiation of treatment on Day 1.

          -  For all males and females of childbearing potential, they should be agreeable to use
             an adequate method of contraception or birth control. For females of child bearing
             potential, a negative pregnancy test within 7 days of start of study drug is required

        Exclusion Criteria

          -  Prior cytotoxic therapy for metastatic or incurable disease.

          -  Patients may have had prior therapy with curative intent for localized disease, if
             their recurrence or disease progression was more than six months from completing prior
             therapy.

          -  HER2 positive adenocarcinoma

          -  Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
             form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          -  Known history of active TB (Bacillus Tuberculosis)

          -  Known additional malignancy that is active. Exceptions include basal cell carcinoma of
             the skin or squamous cell carcinoma of the skin that has undergone potentially
             curative therapy or in situ cervical cancer.

          -  Previous invasive malignancy treated with curative intent less than 3 years from time
             of registration. Exceptions include prostate cancer or basal cell skin cancer.

          -  Active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          -  Known history of, or any evidence of active, non-infectious pneumonitis.

          -  Active infection requiring systemic therapy.

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the trial, interfere with the subject's participation
             for the full duration of the trial, or is not in the best interest of the subject to
             participate, in the opinion of the treating investigator.

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with 12-month progression free survival
Time Frame:12 months
Safety Issue:
Description:This will be measured by number of patients without disease progression at 12 months in the two study arms (patients who receive nivolumab with radiation and those who receive nivolumab alone)

Secondary Outcome Measures

Measure:Number of subjects who receive short course chemotherapy with immunotherapy that achieve 12-month progression free survival
Time Frame:12 months
Safety Issue:
Description:This will be measured by the number of patients without disease progression at 12 months in all enrolled patients.
Measure:Overall Survival, as measured by the rate of survival in patients
Time Frame:2 year
Safety Issue:
Description:In both study arms, and in all patients together, we will examine the rate of survival in patients over time from registration through their treatment
Measure:Occurrence of Significant Toxicity, as measured by Number of Grade 3 and Grade 4 Adverse Events (Combined) Attributable to Immunotherapy
Time Frame:2 year
Safety Issue:
Description:We will measure the rate of grade 3 or 4 adverse events attributable to immunotherapy in both study arms

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Weill Medical College of Cornell University

Last Updated

June 22, 2020