Study Evaluating Efficacy and Safety of FFX Versus Combination of CPI-613 With mFFX in Patients With Metastatic Adenocarcinoma of the Pancreas

NCT03504423 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: PANC003
• Study Type: interventional
• Target: 528
• Locations: 6 countries
• Sites: 74

Brief Summary

A prospective, multicenter, open label, randomized phase III study to evaluate efficacy and safety of FFX versus CPI-613 + mFFX in patients with metastatic adenocarcinoma of the pancreas with age range of 18 to 75 years

Conditions

Pancreatic Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Defined as the duration from the date of randomization to the date of death from any cause

  38 months

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  38 months

• Overall Response Rate (ORR)

  38 months

Study Arms (2)

CPI-613, mFolfirinox

EXPERIMENTAL

CPI-613, mFolfirinox CPI-613 at 500 mg/m2 IV infusion at a rate of 4mL/min via a central venous port on day 1 and 3 of a 14-day cycle. mFolfirinox (given immediately after CPI-613 administration): Oxaliplatin (Eloxatin) at 65 mg/m2 given as a 2 hr IV infusion, Folinic acid at 400 mg/m2 given as a 90 min (1.5hr) infusion immediately after Oxaliplatin, and concurrently with Irinotecan (irinotecan at 140mg/m2 given as a 90 min IV infusion) via a Y-connector, Flurouracil at 400 mg/m2 as bolus followed by a 46 hr infusion at 2400mg/m2 starting immediately after completion of folinic acid and Irinotecan.

Drug: CPI 613, mFolfirinox

Folfirinox

ACTIVE COMPARATOR

Folfirinox Folfirinox: Oxaliplatin (Eloxatin) at 85 mg/m2 given as a 2 hr IV infusion, Folinic acid at 400 mg/m2 given as a 90 min (1.5hr) infusion immediately after Oxaliplatin, and concurrently with Irinotecan (irinotecan at 180mg/m2 given as a 90 min IV infusion) via a Y-connector, Flurouracil at 400 mg/m2 as bolus followed by a 46 hr infusion at 2400mg/m2 starting immediately after completion of folinic acid and Irinotecan.

Drug: Folfirinox

Interventions

CPI 613, mFolfirinox DRUG

CPI-613: 500mg/m2, IV infusion at a rate of 4mL/min via a central venous port. mFolfirinox: given immediately after CPI-613 administration

Also known as: CPI-613,Oxaliplatin, folinic acid, irinotecan, flurouracil

CPI-613, mFolfirinox

Folfirinox DRUG

Folfirinox

Also known as: Oxaliplatin, folinic acid, irinotecan, flurouracil

Folfirinox

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed metastatic Stage IV adenocarcinoma of the pancreas
• No prior treatments for stage IV pancreatic adenocarcinoma (prior adjuvant or neoadjuvant treatment is allowed provided completed \> 6 months prior to disease recurrence)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Male and female patients 18 - 75 years of age
• Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST version 1.1)
• Expected survival \>3 months
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted highly effective contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive(s), intrauterine hormone releasing system (IUS), bilateral tubal occlusion or vasectomized partner) during and for 6 months after last study dose and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation, at monthly interval (day 1 of every even numbered cycle), at the end of systemic exposure, and at 30 days after the systemic exposure
• Males with female partners (of childbearing potential) and female partners (of child bearing potential) with male partners must agree to use double barrier contraceptive measure (a combination of male condom with either cap, diaphragm or sponge with spermicide) in addition to oral contraception or avoidance of intercourse during the study and for 6 months after last study dose is received
• At least 2 weeks must have elapsed from any prior surgery with resolution of any sequela for randomization
• Laboratory values ≤2 weeks prior to randomization must be:
• Adequate hematologic values
• Platelet count ≥100,000 cells/mm3 or ≥100 bil/L;
• Absolute neutrophil count \[ANC\] ≥1,500 cells/mm3 or ≥1.5 bil/L;
• Hemoglobin ≥9 g/dL or ≥90 g/L)
• Adequate hepatic function

You may not qualify if:

• Endocrine or acinar pancreatic carcinoma
• Known cerebral metastases, central nervous system (CNS), or epidural tumor
• Prior treatment with any chemotherapy for metastatic adenocarcinoma of the pancreas
• Completion of a gemcitabine-based adjuvant chemotherapy regimen within less than 6 months at the time of screening.
• Receipt of neoadjuvant or adjuvant FOLFIRINOX therapy if \<6 months prior to disease recurrence
• Patients with hypersensitivity to devimistat, FFX treatment or any of their excipients
• Presence of clinically significant abdominal ascites
• Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 2 weeks prior to initiation of devimistat treatment
• Serious medical illness that would potentially increase patients' risk for toxicity
• Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
• Female patients who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of study treatment
• Female patients of childbearing potential with a positive pregnancy test assessed by a serum pregnancy test at screening
• Female patients of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for 6 months after the last dose of study treatment
• Male patients with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for 6 months after completion of study treatment
• Male patients unwilling to abstain from donating sperm during treatment and for 6 months after completion of study treatment

Sponsors & Collaborators

• Cornerstone Pharmaceuticals: lead

Study Sites (74)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA Medical Center

Los Angeles, California, 90404, United States

Location

Pacific Hematology Oncology Associates

San Francisco, California, 94115, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06511, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Northwestern Memorial Hospital - Arkes Family Pavilion

Chicago, Illinois, 60611, United States

Location

University of Chicago

Harvey, Illinois, 60426, United States

Location

The University of Kansas Cancer Center - Clinical Research Center - Fairway Office Park

Fairway, Kansas, 66205, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Micihgan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos cancer Center

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Cancer Center (MCCC)

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer centers of Nevada

Las Vegas, Nevada, 89148, United States

Location

Englewood Hospital and Medical Center

Englewood, New Jersey, 07631, United States

Location

Atlantic Health System

Morristown, New Jersey, 07962, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Levine cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic - Taussig Cancer Center

Cleveland, Ohio, 44106, United States

Location

University Hospitals - Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh-Hillman cancer ceter

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center-Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Cancer Center - Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22908, United States

Location

VCU Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Blue Ridge Cancer Care

Roanoke, Virginia, 24014, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Hôpital Erasme

Brussels, Brussels Capital, 1070, Belgium

Location

UZ Leuven

Leuven, VBR, 3000, Belgium

Location

CHRU Brest - Hôpital Morvan

Brest, 29609, France

Location

Hôpital Beaujon

Clichy, 92110, France

Location

Centre Hospitalier Départemental Vendée - Hôpital de la Roche-sur-Yon

La Roche-sur-Yon, 85925, France

Location

L'ICM, Institut régional du Cancer de Montpellier

Montpellier, 34000, France

Location

CHU de Nantes - Hôpital Nord Laennec

Nantes, 44093, France

Location

CHU Hopitaux de Bordeaux - Hôpital Saint-André

Pessac, 33600, France

Location

CHU de Poitiers

Poitiers, 86000, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54500, France

Location

Gustave Roussy Cancer Campus Grand Paris (Institut de Cancerologie Gustave-Roussy)

Villejuif, 94805, France

Location

SLK-Kliniken Heilbronn GmbH

Heilbronn, Baden-Wurttemberg, 74078, Germany

Location

Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH

Bochum, 44791, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Hillel Yaffe Medical Center

Hadera, Haifa District, 38101, Israel

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Sanz Medical Center - Laniado Hospital

Netanya, 42150, Israel

Location

The Chaim Sheba Medical Center - Sheba Cancer Research Center (SCRC)

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 62431, Israel

Location

Assaf-Harofeh Medical Center

Ẕerifin, 70300, Israel

Location

The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital)

Seocho, Seoul, South Korea

Location

Seoul National University Hospital

Busan, 49201, South Korea

Location

Kyungpook National University Chilgok Hospital

Daegu, 41944, South Korea

Location

Gachon University Gil Hospital

Incheon, 21556, South Korea

Location

Inha University Hospital

Incheon, 22332, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Korea University Anam Hospital

Seoul, 2841, South Korea

Location

Severance Hospital - Yonsei Cancer Center

Seoul, 3722, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

National Cancer Center

Seoul, 6591, South Korea

Location

Ajou University Hospital

Suwon, 16499, South Korea

Location

Related Publications (3)

• Philip PA, Sahai V, Bahary N, Mahipal A, Kasi A, Rocha Lima CMS, Alistar AT, Oberstein PE, Golan T, Metges JP, Lacy J, Fountzilas C, Lopez CD, Ducreux M, Hammel P, Salem M, Bajor D, Benson AB, Luther S, Pardee T, Van Cutsem E. Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study. J Clin Oncol. 2024 Nov;42(31):3692-3701. doi: 10.1200/JCO.23.02659. Epub 2024 Aug 1.

  PMID: 39088774 DERIVED

• Liu N, Yan M, Tao Q, Wu J, Chen J, Chen X, Peng C. Inhibition of TCA cycle improves the anti-PD-1 immunotherapy efficacy in melanoma cells via ATF3-mediated PD-L1 expression and glycolysis. J Immunother Cancer. 2023 Sep;11(9):e007146. doi: 10.1136/jitc-2023-007146.

  PMID: 37678921 DERIVED

• Philip PA, Buyse ME, Alistar AT, Rocha Lima CM, Luther S, Pardee TS, Van Cutsem E. A Phase III open-label trial to evaluate efficacy and safety of CPI-613 plus modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas. Future Oncol. 2019 Oct;15(28):3189-3196. doi: 10.2217/fon-2019-0209. Epub 2019 Sep 12.

  PMID: 31512497 DERIVED

MeSH Terms

Interventions

devimistat; Leucovorin; Irinotecan; folfirinox; Oxaliplatin

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Sanjeev Luther
• Organization: Cornerstone Pharmaceuticals Inc.

sanjeev.luther@cornerstonepharma.com

585-978-1351

Study Officials

• Philip A Philip, MD, PhD, FRCP

  Karmanos Cancer Institute at Wayne State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2018
• First Posted: April 20, 2018
• Study Start: November 9, 2018
• Primary Completion: August 16, 2021
• Study Completion: January 2, 2022
• Last Updated: January 3, 2023
• Results First Posted: January 3, 2023

Record last verified: 2021-09

Locations

DE (3); US (40); BE (2); IL (7); KR (12); FR (10)