Study Evaluating Efficacy and Safety of FFX Versus Combination of CPI-613 With mFFX in Patients With Metastatic Adenocarcinoma of the Pancreas
- Conditions
- Pancreatic Cancer Metastatic
- Interventions
- Drug: CPI 613, mFolfirinox
- Registration Number
- NCT03504423
- Lead Sponsor
- Cornerstone Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 528
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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)
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Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
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Male and female patients 18 - 75 years of age
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Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST version 1.1)
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Expected survival >3 months
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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
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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
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At least 2 weeks must have elapsed from any prior surgery with resolution of any sequela for randomization
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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.
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Mentally competent, ability to understand and willingness to sign the informed consent form.
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CPI-613, mFolfirinox CPI 613, mFolfirinox 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. Folfirinox Folfirinox 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 38 months Defined as the duration from the date of randomization to the date of death from any cause
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) 38 months 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.Overall Response Rate (ORR) 38 months 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;
Trial Locations
- Locations (73)
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Englewood Hospital and Medical Center
🇺🇸Englewood, New Jersey, United States
Hôpital Erasme
🇧🇪Bruxelles, Brussel, Belgium
UZ Leuven
🇧🇪Leuven, VBR, Belgium
Rambam Medical Center
🇮🇱Haifa, Israel
Hillel Yaffe Medical Center
🇮🇱Hadera, Haifa, Israel
National Cancer Center
🇰🇷Seoul, Korea, Republic of
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Sanz Medical Center - Laniado Hospital
🇮🇱Netanya, Israel
The Chaim Sheba Medical Center - Sheba Cancer Research Center (SCRC)
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Assaf-Harofeh Medical Center
🇮🇱Zerifin, Israel
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Comprehensive Cancer centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Pacific Hematology Oncology Associates
🇺🇸San Francisco, California, United States
Karmanos cancer Center
🇺🇸Detroit, Michigan, United States
Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center-Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Northwestern Memorial Hospital - Arkes Family Pavilion
🇺🇸Chicago, Illinois, United States
The University of Kansas Cancer Center - Clinical Research Center - Fairway Office Park
🇺🇸Fairway, Kansas, United States
University Hospitals - Seidman Cancer Center
🇺🇸Cleveland, Ohio, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Huntsman cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Chicago
🇺🇸Harvey, Illinois, United States
City of Hope
🇺🇸Duarte, California, United States
University of Pittsburgh-Hillman cancer ceter
🇺🇸Pittsburgh, Pennsylvania, United States
University of Virginia Cancer Center - Emily Couric Clinical Cancer Center
🇺🇸Charlottesville, Virginia, United States
Severance Hospital - Yonsei Cancer Center
🇰🇷Seoul, Korea, Republic of
Institut de Cancérologie de Lorraine
🇫🇷Vandœuvre-lès-Nancy, France
Atlantic Health System
🇺🇸Morristown, New Jersey, United States
SLK-Kliniken Heilbronn GmbH
🇩🇪Heilbronn, BW, Germany
University of Cincinnati Cancer Institute
🇺🇸Cincinnati, Ohio, United States
Levine cancer Institute
🇺🇸Charlotte, North Carolina, United States
CHRU Brest - Hôpital Morvan
🇫🇷Brest, France
Hôpital Beaujon
🇫🇷Clichy, France
Gachon University Gil Hospital
🇰🇷Incheon, Korea, Republic of
CHU Hopitaux de Bordeaux - Hôpital Saint-André
🇫🇷Pessac, France
Gustave Roussy Cancer Campus Grand Paris (Institut de Cancerologie Gustave-Roussy)
🇫🇷Villejuif, France
Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
CHU de Poitiers
🇫🇷Poitiers, France
Centre Eugène Marquis
🇫🇷Rennes, France
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
University of Massachusetts Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Mayo Clinic Hospital
🇺🇸Jacksonville, Florida, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
Cleveland Clinic - Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Centre Hospitalier Départemental Vendée - Hôpital de la Roche-sur-Yon
🇫🇷La Roche-sur-Yon, France
CHU de Nantes - Hôpital Nord Laennec
🇫🇷Nantes Cedex 1, France
Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH
🇩🇪Bochum, Germany
L'ICM, Institut régional du Cancer de Montpellier
🇫🇷Montpellier, France
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital)
🇰🇷Seocho, Seoul, Korea, Republic of
VCU Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Micihgan
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Cancer Center (MCCC)
🇺🇸Rochester, Minnesota, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Smilow Cancer Hospital at Yale-New Haven
🇺🇸New Haven, Connecticut, United States