Description:
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.
Title
- Brief Title: PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression
- Official Title: PANGEA: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma
Clinical Trial IDs
- ORG STUDY ID:
IRB14-0141
- NCT ID:
NCT02213289
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Trastuzumab | Herceptin® | ITT-PTS: Personalized Treatment Strategy (HER2 amplified) |
ABT-806 | | ITT-PTS: Personalized Treatment Strategy (EFGR amplified) |
Bemarituzumab | | ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified) |
Ramucirumab | Cyramza | ITT-PTS: Personalized Treatment Strategy (All negative) |
Nivolumab | Opdivo | ITT-PTS: Personalized Treatment Strategy (Immuno-oncology) |
Standard cytotherapy | | ITT-PTS: Personalized Treatment Strategy (All negative) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | - Nivolumab
- Standard cytotherapy
|
ITT-PTS: Personalized Treatment Strategy (HER2 amplified) | Experimental | HER2 amplified. These patients received standard cytotherapy plus Trastuzumab. | - Trastuzumab
- Standard cytotherapy
|
ITT-PTS: Personalized Treatment Strategy (EFGR amplified) | Experimental | EGFR amplified. These patients received ABT-806. | - ABT-806
- Standard cytotherapy
|
ITT-PTS: Personalized Treatment Strategy (FGFR2 amplified) | Experimental | FGFR2 amplified. These patients received standard cytotherapy plus Bemarituzumab. | - Bemarituzumab
- Standard cytotherapy
|
ITT-PTS: Personalized Treatment Strategy (MAPK/PIK3CA aberrant) | Experimental | MAPK/PIK3CA aberrant. These patients received standard cytotherapy plus Ramucirumab. | - Ramucirumab
- Standard cytotherapy
|
ITT-PTS: Personalized Treatment Strategy (EGFR expressing) | Experimental | EGFR expressing. These patients received standard cytotherapy plus ABT 806. | - ABT-806
- Standard cytotherapy
|
ITT-PTS: Personalized Treatment Strategy (All negative) | Experimental | All negative. These patients received standard cytotherapy plus Ramucirumab. | - Ramucirumab
- Standard cytotherapy
|
Non-ITT: Standard Therapy | Other | Patients without monoclonal antibodies available received standard cytotherapy. | |
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall Survival |
Time Frame: | Up to 60 months |
Safety Issue: | |
Description: | Time from enrollment to death from any cause. |
Secondary Outcome Measures
Measure: | Number of Biopsies Leading to an Adverse Event |
Time Frame: | 1 Month |
Safety Issue: | |
Description: | 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). |
Measure: | Completion of Biopsy and Successful, Molecularly-based Treatment Assignment |
Time Frame: | Up to 1 month |
Safety Issue: | |
Description: | 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). |
Measure: | Adverse Event From Serial Biopsy for Second-line Treatment |
Time Frame: | Up to 60 Months |
Safety Issue: | |
Description: | Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis) |
Measure: | Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment |
Time Frame: | Up to 60 months |
Safety Issue: | |
Description: | 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). |
Measure: | Adverse Event From Serial Biopsy for Third-line Treatment |
Time Frame: | Up to 60 months |
Safety Issue: | |
Description: | Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis) |
Measure: | Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment |
Time Frame: | Up to 60 months |
Safety Issue: | |
Description: | 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). |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | University of Chicago |
Trial Keywords
Last Updated
April 8, 2021