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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

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.

Condition or disease Intervention/treatment Phase
Adenocarcinoma Drug: Trastuzumab Drug: ABT-806 Drug: Bemarituzumab Drug: Ramucirumab Drug: Nivolumab Drug: Standard cytotherapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: PANGEA: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma
Actual Study Start Date : January 20, 2015
Actual Primary Completion Date : February 1, 2020
Actual Study Completion Date : August 20, 2020

Arm Intervention/treatment
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.

Drug: Nivolumab
Nivolumab
Other Name: Opdivo

Drug: Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

Experimental: ITT-PTS: Personalized Treatment Strategy (HER2 amplified)
HER2 amplified. These patients received standard cytotherapy plus Trastuzumab.
Drug: Trastuzumab
Trastuzumab
Other Name: Herceptin®

Drug: Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

Experimental: ITT-PTS: Personalized Treatment Strategy (EFGR amplified)
EGFR amplified. These patients received ABT-806.
Drug: ABT-806
ABT-806

Drug: Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

Experimental: ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified)
FGFR2 amplified. These patients received standard cytotherapy plus Bemarituzumab.
Drug: Bemarituzumab
Bemarituzumab

Drug: Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

Experimental: ITT-PTS: Personalized Treatment Strategy (MAPK/PIK3CA aberrant)
MAPK/PIK3CA aberrant. These patients received standard cytotherapy plus Ramucirumab.
Drug: Ramucirumab
Ramucirumab
Other Name: Cyramza

Drug: Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

Experimental: ITT-PTS: Personalized Treatment Strategy (EGFR expressing)
EGFR expressing. These patients received standard cytotherapy plus ABT 806.
Drug: ABT-806
ABT-806

Drug: Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

Experimental: ITT-PTS: Personalized Treatment Strategy (All negative)
All negative. These patients received standard cytotherapy plus Ramucirumab.
Drug: Ramucirumab
Ramucirumab
Other Name: Cyramza

Drug: Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

Non-ITT: Standard Therapy
Patients without monoclonal antibodies available received standard cytotherapy.
Drug: Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 60 months ]
    Time from enrollment to death from any cause.


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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)

  4. 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).

  5. 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)

  6. 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).


Other Outcome Measures:
  1. 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.

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02213289


Locations
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United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
AbbVie
Investigators
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Principal Investigator: Daniel Catenacci, MD University of Chicago
  Study Documents (Full-Text)

Documents provided by University of Chicago:
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02213289    
Other Study ID Numbers: IRB14-0141
First Posted: August 11, 2014    Key Record Dates
Results First Posted: April 8, 2021
Last Update Posted: April 8, 2021
Last Verified: March 2021
Keywords provided by University of Chicago:
Gastric
Esophagogastric
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Nivolumab
Trastuzumab
Ramucirumab
Antineoplastic Agents, Immunological
Antineoplastic Agents