FOLFIRINOX Plus IPI-926 for Advanced Pancreatic Adenocarcinoma

NCT01383538 | Completed Phase 1 DMC

• 1 other identifier: CC#11455
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this phase I study to determine the optimal dose for the combination of IPI-926 plus FOLFIRINOX (5-fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin) chemotherapy in patients with pancreatic cancer.

Conditions

Pancreatic Cancer; Adenocarcinoma; Pancreatic Neoplasms

Keywords

pancreas; cancer; adenocarcinoma; Oxaliplatin; Leucovorin; Irinotecan; 5-FU; IPI-926

Outcome Measures

Primary Outcomes (1)

• The maximum tolerated dose (MTD) for FOLFIRINOX plus IPI-926 in patients with advanced pancreatic cancer.

  Ongoing evaluation through sequential dose cohorts; evaluations at 2-week intervals up to one year.

Secondary Outcomes (3)

• Number of participants with Adverse events and SAEs

  Ongoing evaluation for all patients throughout the course of treatment; evaluations at 2-week intervals up to one year.

• Time to tumor progression

  Efficacy evaluations at 2-month intervals up to one year.

• Objective response rate (ORR) by RECIST criteria

  Efficacy evaluations at 2-month intervals up to one year

Study Arms (1)

FOLFIRINOX Plus IPI-926

EXPERIMENTAL

Drug: FOLFIRINOX, IPI-926

Interventions

FOLFIRINOX, IPI-926 DRUG

Oxaliplatin: intravenous, 50 to 85 mg/m2, over 2 hrs, once per cycle. Leucovorin: intravenous, 400 mg/m2, over 2 hrs, once per cycle. Irinotecan: intravenous, 120 to 180 mg/m2, over 90 minutes, once per cycle. 5-FU: intravenous, 1600 to 2400mg/m2, over 46hr continuous infusion, once per cycle. IPI-926: oral, 130 to 160 mg/day, daily, 14 days per cycle.

Also known as: Oxaliplatin, Leucovorin, Irinotecan, 5-FU

FOLFIRINOX Plus IPI-926

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed pancreatic adenocarcinoma
• Disease that is not operable (locally advanced or metastatic)
• No prior systemic therapy for their diagnosis (except in adjuvant setting \> 6 months previously)
• ECOG performance score of 0-1
• At least 18 years of age
• Evidence of either or both of the following:
• RECIST-defined measurable disease (lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques or ≥10 mm with spiral CT scan)
• An elevated serum CA19-9 at baseline ( ≥ 2X ULN)
• Endobiliary stents, but not percutaneous biliary drains, are permissible.
• Adequate bone marrow function:
• ANC ≥ 1500/uL
• platelet count ≥ 100,000/uL
• hemoglobin ≥ 9.0 g/dL (may be increased to this level with transfusion as long as there is no evidence of active bleeding)
• Adequate hepatic function:
• Total bilirubin ≤ 1.5 X ULN

You may not qualify if:

• Any prior systemic or investigational therapy for metastatic pancreatic cancer. Systemic therapy administered alone or in combination with radiation in the adjuvant setting is permissible as long as it was completed \> 6 months prior to the time of study enrollment.
• Inability to comply with study and/or follow-up procedures.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study.
• Presence of central nervous system or brain metastases.
• Life expectancy \< 12 weeks
• Pregnancy (positive pregnancy test) or lactation.
• Concurrent active malignancy. The following prior malignancies ARE allowed: adequately treated non-melanoma skin cancer; in situ cervical cancer; localized prostate cancer; or adequately treated Stage I or II cancer for which treatment was completed more than one year ago and from which the patient is currently in complete remission; or any other form of cancer from which the patient has been disease-free for 5 years.
• Patients with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
• Known, existing uncontrolled coagulopathy. Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation are eligible IF: they are appropriately anticoagulated and have not had a Grade 2 or greater bleeding episode in the 3 weeks before Day 1. However, as concurrent/pre-existing use of coumadin is not allowed, only low-molecular heparin should be used.
• Pre-existing sensory neuropathy \> grade 1.
• Major surgery within 4 weeks of the start of study treatment, without complete recovery.
• Cirrhotic liver disease, ongoing alcohol abuse, or known chronic active or acute hepatitis.
• Concurrent administration of the medications or foods which are known to inhibit CYP3A activity to a clinically relevant degree (see Appendix 1).
• Known glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Sponsors & Collaborators

• Andrew Ko: lead
• Infinity Pharmaceuticals, Inc.: collaborator

Study Sites (3)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma; Neoplasms

Interventions

folfirinox; IPI-926; Oxaliplatin; Leucovorin; Irinotecan; Fluorouracil

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Andrew Ko, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Department of Medicine (Hematology/Oncology), UCSF

Study Record Dates

• First Submitted: June 20, 2011
• First Posted: June 28, 2011
• Study Start: August 23, 2011
• Primary Completion: December 13, 2012
• Study Completion: May 26, 2015
• Last Updated: August 8, 2017

Record last verified: 2017-08

Locations

US (3)