Clinical trial NCT02213289: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma
Keywords: Gastric
Esophagogastric
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2014-08-11
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall Survival
timeFrame: Up to 60 months
Secondary outcomes:
measure: Number of Biopsies Leading to an Adverse Event
timeFrame: 1 Month
measure: Completion of Biopsy and Successful, Molecularly-based Treatment Assignment
timeFrame: Up to 1 month
measure: Adverse Event From Serial Biopsy for Second-line Treatment
timeFrame: Up to 60 Months
measure: Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment
timeFrame: Up to 60 months
measure: Adverse Event From Serial Biopsy for Third-line Treatment
timeFrame: Up to 60 months
measure: Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment
timeFrame: Up to 60 months
Other outcomes:
measure: First-line Progression-free Survival
timeFrame: Up to 60 Months
measure: Objective Response to First Line Therapy
timeFrame: Up to 6 months
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Daniel Catenacci, MD
role: PRINCIPAL_INVESTIGATOR
References: