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

NCT02213289 | Completed Phase 2 Results DMC

• 1 other identifier: IRB14-0141
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenocarcinoma

Keywords

Gastric; Esophagogastric

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Time from enrollment to death from any cause.

  Up to 60 months

Secondary Outcomes (6)

• Number of Biopsies Leading to an Adverse Event

  1 Month

• Completion of Biopsy and Successful, Molecularly-based Treatment Assignment

  Up to 1 month

• Adverse Event From Serial Biopsy for Second-line Treatment

  Up to 60 Months

• Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment

  Up to 60 months

• Adverse Event From Serial Biopsy for Third-line Treatment

  Up to 60 months

Other Outcomes (2)

• First-line Progression-free Survival

  Up to 60 Months

• Objective Response to First Line Therapy

  Up to 6 months

Study Arms (8)

ITT-PTS: Personalized Treatment Strategy (Immuno-oncology)

EXPERIMENTAL

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; Drug: Standard cytotherapy

ITT-PTS: Personalized Treatment Strategy (HER2 amplified)

EXPERIMENTAL

HER2 amplified. These patients received standard cytotherapy plus Trastuzumab.

Drug: Trastuzumab; Drug: Standard cytotherapy

ITT-PTS: Personalized Treatment Strategy (EFGR amplified)

EXPERIMENTAL

EGFR amplified. These patients received ABT-806.

Drug: ABT-806; Drug: Standard cytotherapy

ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified)

EXPERIMENTAL

FGFR2 amplified. These patients received standard cytotherapy plus Bemarituzumab.

Drug: Bemarituzumab; Drug: Standard cytotherapy

ITT-PTS: Personalized Treatment Strategy (MAPK/PIK3CA aberrant)

EXPERIMENTAL

MAPK/PIK3CA aberrant. These patients received standard cytotherapy plus Ramucirumab.

Drug: Ramucirumab; Drug: Standard cytotherapy

ITT-PTS: Personalized Treatment Strategy (EGFR expressing)

EXPERIMENTAL

EGFR expressing. These patients received standard cytotherapy plus ABT 806.

Drug: ABT-806; Drug: Standard cytotherapy

ITT-PTS: Personalized Treatment Strategy (All negative)

EXPERIMENTAL

All negative. These patients received standard cytotherapy plus Ramucirumab.

Drug: Ramucirumab; Drug: Standard cytotherapy

Non-ITT: Standard Therapy

OTHER

Patients without monoclonal antibodies available received standard cytotherapy.

Drug: Standard cytotherapy

Interventions

Trastuzumab DRUG

Trastuzumab

Also known as: Herceptin®

ITT-PTS: Personalized Treatment Strategy (HER2 amplified)

ABT-806 DRUG

ABT-806

ITT-PTS: Personalized Treatment Strategy (EFGR amplified); ITT-PTS: Personalized Treatment Strategy (EGFR expressing)

Bemarituzumab DRUG

Bemarituzumab

ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified)

Ramucirumab DRUG

Ramucirumab

Also known as: Cyramza

ITT-PTS: Personalized Treatment Strategy (All negative); ITT-PTS: Personalized Treatment Strategy (MAPK/PIK3CA aberrant)

Nivolumab DRUG

Nivolumab

Also known as: Opdivo

ITT-PTS: Personalized Treatment Strategy (Immuno-oncology)

Standard cytotherapy DRUG

FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

ITT-PTS: Personalized Treatment Strategy (All negative); ITT-PTS: Personalized Treatment Strategy (EFGR amplified); ITT-PTS: Personalized Treatment Strategy (EGFR expressing); ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified); ITT-PTS: Personalized Treatment Strategy (HER2 amplified); ITT-PTS: Personalized Treatment Strategy (Immuno-oncology); ITT-PTS: Personalized Treatment Strategy (MAPK/PIK3CA aberrant); Non-ITT: Standard Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic gastric or esophagogastric junction (type I,II,III Siewert) adenocarcinoma
• 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.
• 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.
• ECOG PS 0,1
• Age \> 18 years
• 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

You may not qualify if:

• No CVA within 6 months, no recent MI within 6 months
• No currently active second malignancy
• No uncontrolled intercurrent illness or infection
• No peripheral edema \> grade 2 at baseline.
• No peripheral neuropathy \> grade 2 at baseline.
• No diarrhea \> grade 2 at baseline.

Sponsors & Collaborators

• University of Chicago: lead
• AbbVie: collaborator

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Trastuzumab; depatuxizumab; bemarituzumab; Ramucirumab; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Daniel Catenacci, MD
• Organization: University of Chicago

dcatenac@bsd.uchicago.edu

2-1000

Study Officials

• Daniel Catenacci, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2014
• First Posted: August 11, 2014
• Study Start: January 20, 2015
• Primary Completion: February 1, 2020
• Study Completion: August 20, 2020
• Last Updated: April 8, 2021
• Results First Posted: April 8, 2021

Record last verified: 2021-03

Locations

US (1)