FOLFIRINOX Plus IPI-926 for Advanced Pancreatic Adenocarcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Infinity Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Andrew Ko, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01383538
First received: June 20, 2011
Last updated: March 4, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Adenocarcinoma
Pancreatic Neoplasms
Drug: FOLFIRINOX, IPI-926
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of FOLFIRINOX Plus IPI-926 for Advanced Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • The maximum tolerated dose (MTD) for FOLFIRINOX plus IPI-926 in patients with advanced pancreatic cancer. [ Time Frame: Ongoing evaluation through sequential dose cohorts; evaluations at 2-week intervals up to one year. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with Adverse events and SAEs [ Time Frame: Ongoing evaluation for all patients throughout the course of treatment; evaluations at 2-week intervals up to one year. ] [ Designated as safety issue: Yes ]
  • Time to tumor progression [ Time Frame: Efficacy evaluations at 2-month intervals up to one year. ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) by RECIST criteria [ Time Frame: Efficacy evaluations at 2-month intervals up to one year ] [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: August 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFIRINOX Plus IPI-926 Drug: FOLFIRINOX, IPI-926

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.

Other Names:
  • Oxaliplatin
  • Leucovorin
  • Irinotecan
  • 5-FU

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically-confirmed pancreatic adenocarcinoma
  2. Disease that is not operable (locally advanced or metastatic)
  3. No prior systemic therapy for their diagnosis (except in adjuvant setting > 6 months previously)
  4. ECOG performance score of 0-1
  5. At least 18 years of age
  6. 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)
  7. Endobiliary stents, but not percutaneous biliary drains, are permissible.
  8. 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)
  9. Adequate hepatic function:

    • Total bilirubin ≤ 1.5 X ULN
    • AST (SGOT) ≤ 2.5 X ULN
    • ALT (SGPT) ≤ 2.5 X ULN
  10. Adequate renal function as determined by either:

    • Calculated or measured creatinine clearance ≥ 40 mL/min (for calculated creatinine clearance, Cockcroft-Gault equation will be used). The Modified Cockcroft-Gault formula is as follows:

      [140 - age(yrs)] x [actual weight (kg)] / [72 x serum creatinine (mg/dl)] Note: Multiply by a factor of 0.85 if female

    • Serum creatinine ≤ 1.5 X ULN
  11. Ability to swallow oral medications
  12. All women of child-bearing potential (WCBP), all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study. Women of child-bearing potential (defined as being less than 1 year post-menopausal) must have a negative serum or urine β human chorionic gonadotropin (βhCG) pregnancy test; and men and women of reproductive potential must agree to practice an effective method of avoiding pregnancy while receiving study drug and for 30 days after the final dose of study drug. Effective contraception includes use of oral contraceptives with an additional barrier method, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, and total abstinence.
  13. Ability to understand the nature of this study protocol and give written informed consent
  14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

  1. 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.
  2. Inability to comply with study and/or follow-up procedures.
  3. 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.
  4. Presence of central nervous system or brain metastases.
  5. Life expectancy < 12 weeks
  6. Pregnancy (positive pregnancy test) or lactation.
  7. 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.
  8. Patients with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.
  9. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
  10. 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.
  11. Pre-existing sensory neuropathy > grade 1.
  12. Major surgery within 4 weeks of the start of study treatment, without complete recovery.
  13. Cirrhotic liver disease, ongoing alcohol abuse, or known chronic active or acute hepatitis.
  14. Concurrent administration of the medications or foods which are known to inhibit CYP3A activity to a clinically relevant degree (see Appendix 1).
  15. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  16. Known hypersensitivity reaction to a sulfonamide.
  17. Presence of active infection requiring systemic use of antibiotics within 72 hours of treatment.
  18. Known human immunodeficiency virus (HIV) positivity.
  19. Known hypersensitivity to IPI-926 or any of the excipients in IPI-926 capsules.
  20. Pregnant or lactating women.
  21. Any other co-morbid condition(s) that may interfere with study participation which in the judgment of the Investigator would place the patient at undue risk or interfere with the study. Examples include, but are not limited to sepsis, recent significant traumatic injury, and other conditions.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01383538

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Andrew Ko
Infinity Pharmaceuticals, Inc.
Investigators
Principal Investigator: Andrew Ko, M.D. University of California, San Francisco
  More Information

No publications provided

Responsible Party: Andrew Ko, Associate Professor, Department of Medicine (Hematology/Oncology), UCSF, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01383538     History of Changes
Other Study ID Numbers: CC#11455
Study First Received: June 20, 2011
Last Updated: March 4, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
pancreas
cancer
adenocarcinoma
Oxaliplatin
Leucovorin
Irinotecan
5-FU
IPI-926

Additional relevant MeSH terms:
Adenocarcinoma
Neoplasms
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Leucovorin
Levoleucovorin
Oxaliplatin
Irinotecan
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antidotes
Protective Agents
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014