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

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ClinicalTrials.gov Identifier: NCT02213289
Recruitment Status : Completed
First Posted : August 11, 2014
Results First Posted : April 8, 2021
Last Update Posted : April 8, 2021
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
Results First Submitted Date  ICMJE January 29, 2021
Results First Posted Date  ICMJE April 8, 2021
Last Update Posted Date April 8, 2021
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: March 15, 2021)
Overall Survival [ Time Frame: Up to 60 months ]
Time from enrollment to death from any cause.
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: March 15, 2021)
  • Number of Biopsies Leading to an Adverse Event [ Time Frame: 1 Month ]
    Number of biopsies leading to an adverse event of the total undergoing baseline biopsies of a primary and metastatic disease site (liver, lung, lymph node, peritoneum/carcinomatosis).
  • Completion of Biopsy and Successful, Molecularly-based Treatment Assignment [ Time Frame: Up to 1 month ]
    Completion of biopsies with successful assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS).
  • Adverse Event From Serial Biopsy for Second-line Treatment [ Time Frame: Up to 60 Months ]
    Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis)
  • Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment [ Time Frame: Up to 60 months ]
    Completion of biopsy with successful treatment assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS).
  • Adverse Event From Serial Biopsy for Third-line Treatment [ Time Frame: Up to 60 months ]
    Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis)
  • Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment [ Time Frame: Up to 60 months ]
    Completion of biopsy with successful treatment assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS).
Original 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
Current Other Pre-specified Outcome Measures
 (submitted: March 15, 2021)
  • First-line Progression-free Survival [ Time Frame: Up to 60 Months ]
    Time from enrollment to progression or death during first-line treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
  • Objective Response to First Line Therapy [ Time Frame: Up to 6 months ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
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: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma
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: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adenocarcinoma
Intervention  ICMJE
  • Drug: Trastuzumab
    Trastuzumab
    Other Name: Herceptin®
  • Drug: ABT-806
    ABT-806
  • Drug: Bemarituzumab
    Bemarituzumab
  • Drug: Ramucirumab
    Ramucirumab
    Other Name: Cyramza
  • Drug: Nivolumab
    Nivolumab
    Other Name: Opdivo
  • Drug: Standard cytotherapy
    FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Study Arms  ICMJE
  • Experimental: ITT-PTS: Personalized Treatment Strategy (Immuno-oncology)

    For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows:

    Immuno-oncology included PD-L1 IHC combined positivity score >10, high microsatellite instability, tumor mutation burden >15 mutations per megabase, and/or Epstein-Barr virus positive. These patients received standard cytotherapy plus Nivolumab.

    Interventions:
    • Drug: Nivolumab
    • Drug: Standard cytotherapy
  • Experimental: ITT-PTS: Personalized Treatment Strategy (HER2 amplified)
    HER2 amplified. These patients received standard cytotherapy plus Trastuzumab.
    Interventions:
    • Drug: Trastuzumab
    • Drug: Standard cytotherapy
  • Experimental: ITT-PTS: Personalized Treatment Strategy (EFGR amplified)
    EGFR amplified. These patients received ABT-806.
    Interventions:
    • Drug: ABT-806
    • Drug: Standard cytotherapy
  • Experimental: ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified)
    FGFR2 amplified. These patients received standard cytotherapy plus Bemarituzumab.
    Interventions:
    • Drug: Bemarituzumab
    • Drug: Standard cytotherapy
  • Experimental: ITT-PTS: Personalized Treatment Strategy (MAPK/PIK3CA aberrant)
    MAPK/PIK3CA aberrant. These patients received standard cytotherapy plus Ramucirumab.
    Interventions:
    • Drug: Ramucirumab
    • Drug: Standard cytotherapy
  • Experimental: ITT-PTS: Personalized Treatment Strategy (EGFR expressing)
    EGFR expressing. These patients received standard cytotherapy plus ABT 806.
    Interventions:
    • Drug: ABT-806
    • Drug: Standard cytotherapy
  • Experimental: ITT-PTS: Personalized Treatment Strategy (All negative)
    All negative. These patients received standard cytotherapy plus Ramucirumab.
    Interventions:
    • Drug: Ramucirumab
    • Drug: Standard cytotherapy
  • Non-ITT: Standard Therapy
    Patients without monoclonal antibodies available received standard cytotherapy.
    Intervention: Drug: Standard cytotherapy
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 Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2020)
80
Original Estimated Enrollment  ICMJE
 (submitted: August 8, 2014)
104
Actual Study Completion Date  ICMJE August 20, 2020
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 March 2021

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