PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression
Condition: Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Trastuzumab; ABT-806; Bemarituzumab; Ramucirumab; Nivolumab; Standard cytotherapy
Intervention description: Trastuzumab; ABT-806; Bemarituzumab; Ramucirumab; Nivolumab; FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Intervention MeSH terms: Nivolumab; Trastuzumab; Bemarituzumab; Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastric; Esophagogastric

Summary:

      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.
    

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.