Clinical Trials /

Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer

NCT02830594

Description:

This phase II trial studies how well pembrolizumab and palliative radiation therapy works in treating patients with esophagus, stomach, or gastroesophageal junction cancer that has spread to other parts of the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Palliative radiation therapy, such as external beam radiation therapy, uses high energy beams to treat symptoms that are caused by tumors. Giving pembrolizumab together with palliative radiation therapy may work better in treating patients with esophagus, stomach, or gastroesophageal junction cancer that has spread to other parts of the body.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer
  • Official Title: Combining Pembrolizumab and Palliative Radiotherapy in Gastroesophageal Cancer to Enhance Anti-Tumor T Cell Response and Augment the Abscopal Effect

Clinical Trial IDs

  • ORG STUDY ID: 16099
  • SECONDARY ID: NCI-2016-00686
  • SECONDARY ID: 16099
  • NCT ID: NCT02830594

Conditions

  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Gastric Squamous Cell Carcinoma
  • Metastatic Malignant Neoplasm in the Stomach
  • Stage IV Esophageal Adenocarcinoma
  • Stage IV Esophageal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, RT)

Purpose

This phase II trial studies how well pembrolizumab and palliative radiation therapy works in treating patients with esophagus, stomach, or gastroesophageal junction cancer that has spread to other parts of the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Palliative radiation therapy, such as external beam radiation therapy, uses high energy beams to treat symptoms that are caused by tumors. Giving pembrolizumab together with palliative radiation therapy may work better in treating patients with esophagus, stomach, or gastroesophageal junction cancer that has spread to other parts of the body.

Detailed Description

      PRIMARY OBJECTIVES I. To establish that the combination of pembrolizumab and traditional
      external beam multifractionated radiation therapy (RT) to the primary tumor or a single
      target metastatic site of patients with metastatic gastric, esophageal, and/or
      gastroesophageal junction (GEJ) cancers will lead to an increase in tumor infiltrating
      cytotoxic T-cells and circulating cytotoxic T cells and a reduction in immunosuppressive
      regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in metastatic sites.

      SECONDARY OBJECTIVES:

      I. To establish that the combination of pembrolizumab and RT is feasible in the patient
      population and evaluate toxicities per National Cancer Institute (NCI) Common Toxicity
      Criteria for Adverse Events (CTCAE) version (ver.) 4.03.

      II. To evaluate overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors
      (RECIST) 1.1 and immune related (ir)RECIST in this treatment population and correlate with
      tumor T-cell response.

      III. To evaluate progression-free (PFS) and overall survival (OS) in this treatment
      population.

      TERTIARY OBJECTIVES:

      I. To measure changes in whole genome serum micro ribonucleic acid (miRNA) signature before
      and after protocol therapy and correlate with tumor/immune/stromal cell miRNA expression
      profiling determined by deep sequencing.

      OUTLINE:

      INITIAL TREATMENT: Patients undergo palliative external beam RT daily. On day 1, patients
      undergo the first RT fraction and then receive pembrolizumab intravenously (IV) over 30
      minutes. Courses repeat every 3 weeks for up to 35 courses in the absence of disease
      progression or unacceptable toxicity.

      SECOND PHASE: Patients who achieve a complete response, stop study treatment, and then
      experience radiographic disease progression may be eligible for the second phase at the
      discretion of the investigator if no cancer treatment was administered since the last dose
      of pembrolizumab and trial eligibility safety parameters are met. Patients receive
      pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 17 courses
      in the absence of disease progression or unacceptable toxicity.

      After completion of treatment, patients are followed up at 30 days, every 6 weeks for 1
      year, and then every 9 and 12 weeks for up to 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, RT)ExperimentalINITIAL TREATMENT: Patients undergo palliative external beam RT daily. On day 1, patients undergo the first RT fraction and then receive pembrolizumab intravenously (IV) over 30 minutes. Courses repeat every 3 weeks for up to 35 courses in the absence of disease progression or unacceptable toxicity. SECOND PHASE: Patients who achieve a complete response, stop study treatment, and then experience radiographic disease progression may be eligible for the second phase at the discretion of the investigator if no cancer treatment was administered since the last dose of pembrolizumab and trial eligibility safety parameters are met. Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Documented informed consent of the participant
    
              -  Willing to provide tumor tissue amenable to ultrasound or computed tomography
                 (CT)-guided biopsy for biomarker analyses
    
                   -  Patients with malignant ascites are permitted to participate and provide ascites
                      samples for biomarker analyses
    
                   -  Patients receiving radiation to a single metastatic site in which only the
                      primary tumor is accessible for biopsy by endoscopy will also be eligible
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
    
              -  Life expectancy of >= 3 months
    
              -  Diagnosis of metastatic squamous cell carcinoma and/or adenocarcinoma of the
                 esophagus, gastroesophageal junction, or stomach in need of palliative radiotherapy
                 to the primary tumor or a single metastatic site for symptoms such as pain,
                 dysphagia, and/or gastrointestinal bleeding
    
                 * Patients with adenocarcinoma histology and known human epidermal growth factor
                 receptor 2 (HER2) overexpressing disease are permitted to participate if they
                 progressed or are intolerant of prior trastuzumab-containing therapy
    
              -  Measurable metastatic sites of disease outside of the target lesion undergoing
                 palliative radiation based on RECIST 1.1 as assessed by the investigator
    
              -  Have no limits on prior lines of therapy or may be treatment-naive if in need of
                 palliative RT provided the patient has not received prior anti-programmed cell death
                 protein 1(PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), or anti-programmed
                 cell death 1 ligand 2 (PD-L2) therapy
    
              -  Absolute neutrophil count (ANC) >= 1,500/mm^3
    
              -  Platelets >= 100,000/mm^3
    
              -  Hemoglobin >= 9 g/dL
    
                 * May receive transfusion to meet this goal
    
              -  Total serum bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN
                 if total bilirubin levels > 1.5 x ULN
    
              -  Albumin >= 2.5 mg/dL
    
              -  Aspartate aminotransaminase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN OR
                 =< 5.0 x ULN if liver metastases present
    
              -  Serum creatinine =< 1.5 x ULN OR creatinine clearance (if measured or calculated per
                 institutional standard) >= 60 mL/min if creatinine levels > 1.5 x ULN
    
                   -  Glomerular filtration rate (GFR) can also be used in place of creatinine or
                      creatinine clearance (CrCl)
    
              -  If not receiving anticoagulants: international normalized ratio (INR) OR prothrombin
                 (PT) =< 1.5 x ULN; if on anticoagulant therapy: PT must be within therapeutic range
                 of intended use of anticoagulants
    
              -  If not receiving anticoagulants: activated partial thromboplastin time (aPTT) =< 1.5
                 x ULN; if on anticoagulant therapy: aPTT must be within therapeutic range of intended
                 use of anticoagulants
    
              -  Negative urine or serum pregnancy test (female of childbearing potential only)
    
                 * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
                 test will be required
    
              -  Female of childbearing potential: willing to use 2 methods of birth control or be
                 surgically sterile, or abstain from heterosexual activity for the course of the study
                 through 120 days after the last dose of study medication
    
                 * Childbearing potential defined as not being surgically sterilized or have not been
                 free from menses for > 1 year
    
              -  Male: use an adequate method of contraception starting with the first dose of study
                 therapy through 120 days after the last dose of study therapy
    
            Exclusion Criteria:
    
              -  Anti-PD-1, anti-PD-L1, or anti-PD-L2 agents
    
              -  Prior radiation therapy within the field of the target lesion that in the opinion of
                 the treating radiation oncologist would preclude further palliative radiation to a
                 dose of 30 gray (Gy)
    
              -  Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has
                 not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents
                 administered more than 4 weeks earlier
    
              -  Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks
                 prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from
                 adverse events due to a previously administered agent
    
                   -  Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and
                      may qualify for the study
    
                   -  If subject received major surgery, they must have recovered adequately from the
                      toxicity and/or complications from the intervention prior to starting therapy
    
              -  Live vaccine within 30 days of planned start of study therapy
    
                 * Note: Seasonal influenza vaccines for injection are generally inactivated flu
                 vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are
                 live attenuated vaccines, and are not allowed
    
              -  Immunosuppressive therapy within 7 days prior to the first dose of trial treatment
    
              -  Investigational device within 4 weeks of the first dose of treatment
    
              -  Currently receiving an investigational agent
    
              -  About to undergo palliative radiation for a symptomatic central nervous system (CNS)
                 metastasis
    
              -  Systemic steroid therapy
    
              -  Hypersensitivity to pembrolizumab or any of its excipients
    
              -  Diagnosis of immunodeficiency
    
              -  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 (e.g., 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
    
              -  Current active infection requiring systemic therapy
    
              -  Known history of active tuberculosis (TB), human immunodeficiency virus (HIV) 1/2,
                 hepatitis B or hepatitis C
    
              -  Known additional malignancy that is progressing or requires active treatment
    
                 * 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
    
              -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
    
                 * Subjects with previously treated brain metastases may participate provided they are
                 stable, have no evidence of new or enlarging brain metastases, and are not using
                 steroids for at least 7 days prior to trial treatment; this exception does not
                 include carcinomatous meningitis which is excluded regardless of clinical stability
    
              -  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
    
              -  Pregnant or breastfeeding (female only)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Biomarkers: Comparison of Molecular Biomarkers and Disease Outcome
    Time Frame:Baseline to 18 weeks
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Safety: Incidence of Adverse Events, Serious Adverse Events, and Treatment Delays
    Time Frame:Up to 36 months
    Safety Issue:
    Description:
    Measure:ORR assessed by RECIST 1.1 and irRECIST
    Time Frame:Up to 36 months
    Safety Issue:
    Description:
    Measure:OS
    Time Frame:Up to 36 months
    Safety Issue:
    Description:Will be determined using the Kaplan-Meier method.
    Measure:PFS
    Time Frame:Up to 36 months
    Safety Issue:
    Description:Will be determined using the Kaplan-Meier method.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:City of Hope Medical Center

    Last Updated

    March 31, 2017