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Pancreatic Cancer MetastaticPhase 3NCT03504423

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

A Phase 3 study testing CPI 613, mFolfirinox and Folfirinox in people with Pancreatic Cancer Metastatic, run by Cornerstone Pharmaceuticals at 74 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pancreatic Cancer Metastatic
What is being tested?
CPI 613, mFolfirinox and Folfirinox
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
528 participants
Where
74 sitesin 6 countries
Study dates
9 Nov 2018to 2 Jan 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 23Show fewer
  • 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
  • Aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL] (≤5x UNL if liver metastases present)
  • Alanine aminotransferase [ALT/SGPT] ≤3x UNL (≤5x UNL if liver metastases present)
  • Bilirubin (≤1.5x UNL); bilirubin ≤ 2.5 x ULN for subjects with Gilbert's syndrome
  • Serum albumin > 3.0 g/dL
  • Adequate renal function serum creatinine clearance CLcr > 30 mL/min). (Cocroft-Gault Formula should be used for CrCl calculation)
  • Adequate coagulation function • International Normalized Ratio or INR must be <1.5 unless on therapeutic blood thinners)
  • No evidence of active infection and no serious infection within the past 30 days.
  • Mentally competent, ability to understand and willingness to sign the informed consent form.

Who cannot join

  • 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
Show all 53Show fewer
  • 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
  • Life expectancy less than 3 months
  • Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
  • Unwilling or unable to follow protocol requirements
  • Active heart disease including but not limited to symptomatic congestive heart failure (NYHA class 3 or 4), symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarction
  • Patients with a history of myocardial infarction that is <3 months prior to registration
  • Evidence of active infection, or serious infection within the past 30 days.
  • Patients with known HIV infection
  • Patients who have received cancer immunotherapy of any type within the past 2 weeks prior to initiation of devimistat treatment (steroids given for supportive care or in response to allergic reactions are allowed at any time)
  • Requirement for immediate palliative surgery, radiation or chemotherapy of any kind. Stenting for bile duct obstruction and need for pain medications are allowed provided all other inclusion criteria are met
  • Prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated cancer from which the patient has been disease-free for at least 3 years prior to screening
  • Unwilling or unable to avoid the concomitant use of strong CYP3A4 inducers or inhibitors during treatment with irinotecan
  • A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula (i.e. QTcF)
  • A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of long QT syndrome)
  • The use of concomitant medications that prolong the QT/QTc intervals
  • Contraindications to any of the FFX treatment as follows:
  • Folinic Acid
  • Calcium Folinate is contraindicated in patients who have previously shown hypersensitivity to folinate or any of the excipients.
  • Calcium Folinate Injection is contraindicated in the treatment of pernicious anemia or other megaloblastic anemias where vitamin B12 is deficient. Its use can lead to an apparent response of the hematopoietic system, but neurological damage may occur or progress if already present.
  • Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take calcium folinate tablets.
  • Fluorouracil/5FU
  • Fluorouracil is contraindicated in patients who have any known hypersensitivity to fluorouracil, are seriously debilitated or are suffering from bone marrow depression after radiotherapy or treatment with other antineoplastic agents, or who are suffering from a potentially serious infection.
  • Fluorouracil is strictly contraindicated in pregnant or breast-feeding women.
  • Flourouracil should not be used in the management of non-malignant disease.
  • Fluorouracil must not be taken or used concomitantly with brivudin, sorivudine and analogues. Brivudin, sorivudine and analogues are potent inhibitors of the enzyme dihydropyrimidine dehydrogenase (DPD) which degrades fluorouracil
  • In patients with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity
  • Oxaliplatin
  • Oxaliplatin is contraindicated in patients who have a known history of hypersensitivity to oxaliplatin or to any of the excipients
  • are breast-feeding.
  • have myelosuppression prior to starting first course, as evidenced by baseline neutrophils <2x109/l and/or platelet count of <100x109l.
  • have a peripheral sensitive neuropathy with functional impairment prior to first course.
  • have a severely impaired renal function (creatinine clearance less than 30 ml /min)
  • Irinotecan
  • Chronic inflammatory bowel disease and/or bowel obstruction
  • History of severe hypersensitivity reactions to Irinotecan hydrochloride trihydrate or to any of the excipients
  • Bilirubin > 3 times the ULN
  • Severe bone marrow failure.
  • WHO performance status > 2.
  • Concomitant use with St John's wort

Trial locations and contacts

74 sites in 6 countries.

74 sites in 6 countries

United States40 sites

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • University of Micihgan

    Ann Arbor, Michigan, 48109

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Levine cancer Institute

    Charlotte, North Carolina, 28204

  • University of Virginia Cancer Center - Emily Couric Clinical Cancer Center

    Charlottesville, Virginia, 22908

  • Northwestern Memorial Hospital - Arkes Family Pavilion

    Chicago, Illinois, 60611

  • University of Cincinnati Cancer Institute

    Cincinnati, Ohio, 45267

  • Cleveland Clinic - Taussig Cancer Center

    Cleveland, Ohio, 44106

  • University Hospitals - Seidman Cancer Center

    Cleveland, Ohio, 44106

  • Karmanos cancer Center

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • Englewood Hospital and Medical Center

    Englewood, New Jersey, 07631

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

    Fairway, Kansas, 66205

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • University of Chicago

    Harvey, Illinois, 60426

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Hospital

    Jacksonville, Florida, 32224

  • Comprehensive Cancer centers of Nevada

    Las Vegas, Nevada, 89148

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • UCLA Medical Center

    Los Angeles, California, 90404

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Atlantic Health System

    Morristown, New Jersey, 07962

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

    Nashville, Tennessee, 37232

  • Smilow Cancer Hospital at Yale-New Haven

    New Haven, Connecticut, 06511

  • New York University Langone Medical Center

    New York, New York, 10016

  • University of Pittsburgh-Hillman cancer ceter

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • VCU Massey Cancer Center

    Richmond, Virginia, 23298

  • Blue Ridge Cancer Care

    Roanoke, Virginia, 24014

  • Mayo Clinic Cancer Center (MCCC)

    Rochester, Minnesota, 55905

  • Huntsman cancer Institute

    Salt Lake City, Utah, 84112

  • Pacific Hematology Oncology Associates

    San Francisco, California, 94115

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University

    St Louis, Missouri, 63110

  • Stony Brook University Hospital

    Stony Brook, New York, 11794

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85724

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27157

  • University of Massachusetts Memorial Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

South Korea12 sites

  • Seoul National University Hospital

    Busan, 49201

  • Kyungpook National University Chilgok Hospital

    Daegu, 41944

  • Gachon University Gil Hospital

    Incheon, 21556

  • Inha University Hospital

    Incheon, 22332

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

    Seocho, Seoul

  • Seoul National University Bundang Hospital

    Seongnam-si, 13620

  • Seoul National University Hospital

    Seoul, 03080

  • Korea University Anam Hospital

    Seoul, 2841

  • Severance Hospital - Yonsei Cancer Center

    Seoul, 3722

  • Samsung Medical Center

    Seoul, 6351

  • National Cancer Center

    Seoul, 6591

  • Ajou University Hospital

    Suwon, 16499

Other trials in South Korea

France10 sites

  • CHRU Brest - Hôpital Morvan

    Brest, 29609

  • Hôpital Beaujon

    Clichy, 92110

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

    La Roche-sur-Yon, 85925

  • L'ICM, Institut régional du Cancer de Montpellier

    Montpellier, 34000

  • CHU de Nantes - Hôpital Nord Laennec

    Nantes, 44093

  • CHU Hopitaux de Bordeaux - Hôpital Saint-André

    Pessac, 33600

  • CHU de Poitiers

    Poitiers, 86000

  • Centre Eugène Marquis

    Rennes, 35042

  • Institut de Cancérologie de Lorraine

    Vandœuvre-lès-Nancy, 54500

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

    Villejuif, 94805

Other trials in France

Israel7 sites

  • Hillel Yaffe Medical Center

    Hadera, Haifa District, 38101

  • Rambam Medical Center

    Haifa, 31096

  • Shaare Zedek Medical Center

    Jerusalem, 91031

  • Sanz Medical Center - Laniado Hospital

    Netanya, 42150

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

    Ramat Gan, 52621

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 62431

  • Assaf-Harofeh Medical Center

    Tsrifin, 70300

Other trials in Israel

Germany3 sites

  • Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH

    Bochum, 44791

  • SLK-Kliniken Heilbronn GmbH

    Heilbronn, Baden-Wurttemberg, 74078

  • Universitaetsklinikum Tuebingen

    Tübingen, 72076

Other trials in Germany

Belgium2 sites

  • Hôpital Erasme

    Brussels, Brussels Capital, 1070

  • UZ Leuven

    Leuven, VBR, 3000

Other trials in Belgium

About this study

Official title: A Phase III Multicenter Open-label Randomized Trial to Evaluate Efficacy and Safety of Folfirinox (FFX) Versus Combination of CPI-613 With Modified Folfirinox (mFFX) in Patients With Metastatic Adenocarcinoma of the Pancreas

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

Being tested
CPI 613, mFolfirinox, Folfirinox

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CPI 613, mFolfirinoxDrug

    Also called CPI-613,Oxaliplatin, folinic acid, irinotecan, flurouracil

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

  • FolfirinoxDrug

    Also called Oxaliplatin, folinic acid, irinotecan, flurouracil

    Folfirinox

Study groups in NCT03504423
Study groupRoleWhat they receive
CPI-613, mFolfirinoxExperimentalCPI-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.
Receives: Drug: CPI 613, mFolfirinox
FolfirinoxActive comparatorFolfirinox 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.
Receives: Drug: Folfirinox

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

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

    Measured: 38 months

Secondary outcomes (2)

  1. Progression Free Survival (PFS)

    Defined as the duration from the date of randomization to the date of progressive disease or death from any cause.

    Progressive Disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.

    Measured: 38 months

  2. Overall Response Rate (ORR)

    Defined as the rate of Complete Response (CR) plus Partial Response (PR): Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least 30% decrease in the sum of diameters of target lesions;

    Measured: 38 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2018
  2. Study start9 Nov 2018
  3. Primary completion16 Aug 2021
  4. Study completion2 Jan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
528 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03504423
Sponsor's protocol ID
PANC003
Status last verified
Sep 2021
First submitted
12 Apr 2018
Last updated
3 Jan 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 39088774

  • 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.

    PubMed 37678921

  • 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.

    PubMed 31512497

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CPI 613, mFolfirinox and Folfirinox in people with Pancreatic Cancer Metastatic, run by Cornerstone Pharmaceuticals at 74 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 53 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 74 sites in United States, South Korea, France, Israel, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: 38 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03504423, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2023.

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