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

Adenocarcinoma Clinical Trial

Official title:

PANGEA: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02213289
• Other study ID #: IRB14-0141
• Status: Completed
• Phase: Phase 2
• Start date: January 20, 2015
• Est. completion date: August 20, 2020

Study information

• Verified date: March 2021
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 20, 2020
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma

Intervention

Drug:
• Trastuzumab
Trastuzumab
• ABT-806
ABT-806
• Bemarituzumab
Bemarituzumab
• Ramucirumab
Ramucirumab
• Nivolumab
Nivolumab
• Standard cytotherapy
FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Chicago	AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	First-line Progression-free Survival	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.	Up to 60 Months
Other	Objective Response to First Line Therapy	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.	Up to 6 months
Primary	Overall Survival	Time from enrollment to death from any cause.	Up to 60 months
Secondary	Number of Biopsies Leading to an Adverse Event	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).	1 Month
Secondary	Completion of Biopsy and Successful, Molecularly-based Treatment Assignment	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).	Up to 1 month
Secondary	Adverse Event From Serial Biopsy for Second-line Treatment	Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis)	Up to 60 Months
Secondary	Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment	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).	Up to 60 months
Secondary	Adverse Event From Serial Biopsy for Third-line Treatment	Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis)	Up to 60 months
Secondary	Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment	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).	Up to 60 months