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PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression

NCT02213289

Description:

The purpose of this study is to determine if doctors can use the results of special tests of subjects tumor tissue, that will look for specific abnormalities in the tumor, to choose a specific drug that is targeted to work against that abnormality (called molecular profiling) and to see what effects (good and/or bad) that targeted drug has on subjects cancer when it is given with standard chemotherapy.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression
  • Official Title: PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression

Clinical Trial IDs

  • ORG STUDY ID: IRB14-0141
  • NCT ID: NCT02213289

Conditions

  • Adenocarcinoma

Interventions

DrugSynonymsArms
TrastuzumabHerceptin®HER2 Group
ABT-806EGFR Arm
TBD2FGFR2 Arm
RamucirumabCyramzaVEGFR2 Arm
NivolumabOpdivoMSI-H Arm

Purpose

The purpose of this study is to determine if doctors can use the results of special tests of subjects tumor tissue, that will look for specific abnormalities in the tumor, to choose a specific drug that is targeted to work against that abnormality (called molecular profiling) and to see what effects (good and/or bad) that targeted drug has on subjects cancer when it is given with standard chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
HER2 GroupExperimentalTrastuzumab
  • Trastuzumab
MET groupExperimental
    EGFR ArmExperimentalABT-806
    • ABT-806
    FGFR2 ArmExperimentalTBD2
    • TBD2
    VEGFR2 ArmExperimentalRamucirumab
    • Ramucirumab
    MSI-H ArmExperimentalNivolumab
    • Nivolumab

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Histologically confirmed metastatic gastric or esophagogastric junction (type I,II,III
                 Siewert) adenocarcinoma
    
              2. Newly-diagnosed chemo-naïve or recurrent after curative-intent surgery
    
                   -  >6 months after completion of adjuvant therapy (including chemotherapy and/or
                      radiotherapy)
    
                   -  No prior treatment with any targeted agent
    
                   -  Patients who have started first line mFOLFOX6 therapy (+/-trastuzumab for HER2
                      amplified tumors) may be considered for trial participation if they have received
                      no more than 4 doses of therapy at the time of consent and screening.
    
              3. Measurable metastatic disease by RECIST criteria,
    
                   -  Must be amenable to ultrasound or CT-guided biopsy of one metastatic lesion
    
                   -  Peritoneal disease as the sole site of occult metastasis or presenting as
                      malignant ascites is acceptable if a cell block of tumor cells can be obtained
                      showing >20% viable tumor cells.
    
              4. ECOG PS 0,1
    
              5. Age > 18 years
    
              6. Patients must have normal organ and marrow function as defined below:
    
                   -  granulocytes >1,2500/mcL
    
                   -  platelets >100,000/mcL
    
                   -  total bilirubin < 1.5 x ULN, <1.8 x ULN with liver metastases
    
                   -  AST(SGOT)/ALT(SGPT) <2.5 X ULN without liver metastases; <5 X ULN with liver
                      metastases
    
                   -  creatinine within normal institutional limits (<1.5) OR
    
                   -  creatinine clearance >50 mL/min/1.73m2, (for creatinine level above normal)
    
                   -  INR: < 1.5 (patients on warfarin need to be converted to LMWH during study
                      participation to be eligible)
    
              7. Consent to baseline metastatic and progressive disease biopsy (of
                 metastatic/progressing lesion) for enabling biomarker assessment and treatment
                 assignment (at each time point - baseline, PD1, PD2, PD3) as well as for correlative
                 studies.
    
                 • Consent to baseline and serial blood draws for plasma/serum/whole blood banking for
                 correlative studies
    
              8. Ability to understand and the willingness to sign a written informed consent document
                 and consent to the serial nature of the proposed PANGEA treatment with first, second
                 and third line therapy as tolerated.
    
              9. Ability to comply with requirements of the protocol, as assessed by the investigator
                 by the patient signing the consent form.
    
             10. If history of exposure to anthracyclines during perioperative treatment, the following
                 cumulative doses of anthracyclines must be less than:
    
                 Epirubicin < 720 mg/m2 Doxorubicin or liposomal doxorubicin < 360 mg/m2 Mitoxantrone >
                 120 mg/m2 and idarubicin > 90 mg/m2 If more than one anthracycline has been used, then
                 the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
    
             11. Cardiac Ejection Fraction >50% (for HER2+ patients) as assessed by echocardiogram,
                 MUGA scan, or cardiac MRI
    
             12. Willingness to use effective and reliable methods of contraception (For appropriate
                 methods of contraception considered acceptable see Appendix B).
    
            Both men and women and members of all races and ethnic groups are eligible for this trial.
    
            Exclusion Criteria:
    
              1. No CVA within 6 months, no recent MI within 6 months
    
              2. No currently active second malignancy
    
              3. No uncontrolled intercurrent illness or infection
    
              4. No peripheral edema > grade 2 at baseline.
    
              5. No peripheral neuropathy > grade 2 at baseline.
    
              6. No diarrhea > grade 2 at baseline.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Median Overall Survival
    Time Frame:Improve from 12 Months to 18 months
    Safety Issue:
    Description:To determine the median overall survival (mOS) of the combined HER2+, EGFR+, MSI-H, and VEGFR2+ groups treated with trastuzumab and rilotumumab, respectively, with each line of cytotoxic chemotherapy (up to three lines, Biologic Beyond Progression), compared to historical controls having an aggregate mOS of approximately 12 months.

    Secondary Outcome Measures

    Measure:Safety and Feasibility of Baseline Biopsies
    Time Frame:12 Months
    Safety Issue:
    Description:Number of participants with adverse events of the total undergoing baseline biopsy of a metastatic disease site (liver, lung, lymph node, peritoneum/carcinomatosis) as a measure of safety and tolerability
    Measure:Safety and Feasibility of Conducting Serial Biopsies
    Time Frame:12 Months
    Safety Issue:
    Description:Number of participants with adverse events of the total undergoing serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis) as a measure of safety and tolerability

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Chicago

    Trial Keywords

    • Gastric
    • Esophagogastric

    Last Updated