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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02213289
Recruitment Status : Active, not recruiting
First Posted : August 11, 2014
Last Update Posted : February 20, 2020
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
University of Chicago

Tracking Information
First Submitted Date  ICMJE August 1, 2014
First Posted Date  ICMJE August 11, 2014
Last Update Posted Date February 20, 2020
Actual Study Start Date  ICMJE January 20, 2015
Actual Primary Completion Date February 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2017)
Median Overall Survival [ Time Frame: Improve from 12 Months to 18 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 8, 2014)
Median Overall Survival [ Time Frame: 12 Months ]
To determine the median overall survival (mOS) of the combined HER2+ and MET+ 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2014)
  • Safety and Feasibility of Baseline Biopsies [ Time Frame: 12 Months ]
    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
  • Safety and Feasibility of Conducting Serial Biopsies [ Time Frame: 12 Months ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 6, 2017)
Median Overall Survival Comparison [ Time Frame: 12 Months ]
To determine the median overall survival (mOS) collectively of all patients undergoing tumor molecular profiling with classification into one of six predefined gastroesophageal cancer (GEC) 'oncogenic driver' categories (HER2+, MET+, FGFR2+, VEGFR2+,MSI-H, and EGFR+) with paired specific targeted therapy via the biomarker assessment and treatment algorithm, along with standard chemotherapy (up to 3 lines), compared to historical controls having an aggregate mOS of approximately 12 months.
Original Other Pre-specified Outcome Measures
 (submitted: August 8, 2014)
Median Overall Survival Comparison [ Time Frame: 12 Months ]
To determine the median overall survival (mOS) collectively of all patients undergoing tumor molecular profiling with classification into one of five predefined gastroesophageal cancer (GEC) 'oncogenic driver' categories (HER2+, MET+, FGFR2+, KRAS/PI3K-like, and EGFR/HER3+) with paired specific targeted therapy via the biomarker assessment and treatment algorithm, along with standard chemotherapy (up to 3 lines), compared to historical controls having an aggregate mOS of approximately 12 months.
 
Descriptive Information
Brief Title  ICMJE PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression
Official Title  ICMJE PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adenocarcinoma
Intervention  ICMJE
  • Drug: Trastuzumab
    HER2 Group: FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line) + Trastuzumab
    Other Name: Herceptin®
  • Drug: ABT-806
    EGFR Group: FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)+ ABT-806
  • Drug: TBD2
    FGFR2 Group: FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)+ TBD2
  • Drug: Ramucirumab
    VEGFR2 Group: FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)+ Ramucirumab
    Other Name: Cyramza
  • Drug: Nivolumab
    MSI-H Group: FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)+ Nivolumab
    Other Name: Opdivo
Study Arms  ICMJE
  • Experimental: HER2 Group
    Trastuzumab
    Intervention: Drug: Trastuzumab
  • Experimental: MET group
  • Experimental: EGFR Arm
    ABT-806
    Intervention: Drug: ABT-806
  • Experimental: FGFR2 Arm
    TBD2
    Intervention: Drug: TBD2
  • Experimental: VEGFR2 Arm
    Ramucirumab
    Intervention: Drug: Ramucirumab
  • Experimental: MSI-H Arm
    Nivolumab
    Intervention: Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 18, 2020)
80
Original Estimated Enrollment  ICMJE
 (submitted: August 8, 2014)
104
Estimated Study Completion Date  ICMJE February 1, 2022
Actual Primary Completion Date February 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02213289
Other Study ID Numbers  ICMJE IRB14-0141
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Chicago
Study Sponsor  ICMJE University of Chicago
Collaborators  ICMJE AbbVie
Investigators  ICMJE
Principal Investigator: Daniel Catenacci, MD University of Chicago
PRS Account University of Chicago
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP