A Phase I/II Open-Label Dose-Escalation Clinical Trial of CPI-613 in Combination With Gemcitabine in Cancer Patients

The objectives of this study are:

• To determine the safety and MTD of CPI-613, when used in combination with Gemcitabine, in cancer patients.
• To compare the safety and efficacy of CPI-613/Gemcitabine combination vs. Gemcitabine alone in patients with carcinoma of the pancreas.

Study Overview

• Status: Terminated
• Conditions: Cancer; Pancreatic Cancer; Pancreatic Carcinoma
• Intervention / Treatment: Drug: CPI-613; Drug: CPI-613; Drug: Gemcitabine; Drug: Gemcitabine

Detailed Description

CPI-613, the investigational drug, is a novel anti-tumor compound believed to operate via a novel mechanism of action that does not belong to any existing pharmacological class of anticancer agents currently being used in the clinics. Specifically, CPI-613 is Cornerstone Pharmaceutical Inc.'s lead drug from its Altered Energy Metabolism-Directed (AEMD) technology platform. It is selective against tumor cells (but not normal cells)according to preclinical studies.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10469
      • Eastchester Center for Cancer Care
  • Texas
    • Dallas, Texas, United States, 75201
      • Mary Crowley Cancer Research Centers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For Stages 1 and 2 of the study, histologically documented unresectable primary or metastatic carcinoma of the pancreas, Stage II-IV, diagnosed within the past 8 weeks, intended to be treated with Gemcitabine as a single agent at 1000 mg/m^2 once weekly for 3 weeks repeating the cycle every 4 weeks. For Stage 1 but not Stage 2 of the study, patients also include those with histologically documented unresectable primary or metastatic carcinoma other than pancreatic carcinoma (e.g., bladder cancer, NSCLC, and biliary tract cancer) who are intended to be treated with Gemcitabine as a single agent at 1000 mg/m^2 once weekly for 3 weeks repeating the cycle every 4 weeks, regardless if Gemcitabine is used as second, third or fourth line treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status being 0-2.
• Expected survival >2 months.
• 18-70 years of age of both genders
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.
• Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists.
• No radiotherapy, treatment with cytotoxic agents or chemotherapeutic agents (except CPI-613), or treatment with biologic agents within the 2 weeks prior to treatment with CPI-613. At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. Patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤Grade 1 are eligible, but must be documented as such.

• Laboratory values ≤2 weeks must be:

  • Adequate hematologic (white blood cell [WBC] ≥3500 cells/mm^3 or ≥3.5 bil/L; platelet count ≥150,000 cells/mm^3 or ≥150 bil/L; absolute neutrophil count [ANC] ≥1500 cells/mm3 or ≥1.5 bil/L; and hemoglobin ≥9 g/dL or ≥90 g/L).
  • Adequate hepatic function (aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL], alanine aminotransferase [ALT/SGPT] ≤3x UNL (≤5x UNL if liver metastases present), bilirubin ≤3x UNL).
  • Adequate renal function (serum creatinine ≤2.0 mg/dL or 177 µmol/L).
  • Adequate coagulation (International Normalized Ratio or INR must be≤1.5)
• No evidence of active infection and no serious infection within the past month.
• Mentally competent, ability to understand and willingness to sign the informed consent form.

Exclusion Criteria:

• Prior therapy with Gemcitabine
• Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity.
• Patients with active central nervous system (CNS) or epidural tumor.
• Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease).
• Pregnant women, or women of child-bearing potential not using reliable means of contraception (because the teratogenic potential of CPI-613 is unknown).
• Lactating females.
• Fertile men unwilling to practice contraceptive methods during the study period.
• Life expectancy less than 2 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.
• Dyspnea with minimal to moderate exertion. Patients with large pleural, pericardial, or peritoneal effusions.
• Active heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, arrhythmias requiring medication, or symptomatic congestive heart failure.
• Albumin <2.5 g/dL or <25 g/L.
• Evidence of active infection, or serious infection within the past month.
• Patients with known HIV infection.
• Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 4 weeks prior to initiation of CPI-613 treatment.
• Patients who have received immunotherapy of any type within the past 4 weeks prior to initiation of CPI-613 treatment.
• Requirement for immediate palliative treatment of any kind including surgery.
• Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months.
• A marked baseline prolongation of QT/QTc interval (e.g., repeated exhibition of a QTc interval >470 ms.)
• A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Prior illicit drug addiction.
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of the patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I, Arm A; CPI-613 + Gemcitabine	Drug: CPI-613; IV infusion of CPI-613 given on Days 1,4, 8, 11, 15, 18, of 28 day cycle in cancer patients.; Drug: CPI-613; IV infusion of CPI-613 given on Days 1, 4, 8, 11, 15, 18, of 28 day cycle in patients with pancreatic carcinoma.; Drug: Gemcitabine; IV infusion of 1000 mg/m^2 of Gemcitabine given on Days 1, 8, and 15 of a 28 day cycle in patients with pancreatic carcinoma.; Drug: Gemcitabine; IV infusion of 1000 mg/m^2 of Gemcitabine given on Days 1, 8, and 15 of a 28 day cycle in cancer patients.
Experimental: Phase II, Arm A; CPI-613 + Gemcitabine	Drug: CPI-613; IV infusion of CPI-613 given on Days 1,4, 8, 11, 15, 18, of 28 day cycle in cancer patients.; Drug: CPI-613; IV infusion of CPI-613 given on Days 1, 4, 8, 11, 15, 18, of 28 day cycle in patients with pancreatic carcinoma.; Drug: Gemcitabine; IV infusion of 1000 mg/m^2 of Gemcitabine given on Days 1, 8, and 15 of a 28 day cycle in patients with pancreatic carcinoma.; Drug: Gemcitabine; IV infusion of 1000 mg/m^2 of Gemcitabine given on Days 1, 8, and 15 of a 28 day cycle in cancer patients.
Active Comparator: Phase II, Arm B; Gemcitabine	Drug: Gemcitabine; IV infusion of 1000 mg/m^2 of Gemcitabine given on Days 1, 8, and 15 of a 28 day cycle in patients with pancreatic carcinoma.; Drug: Gemcitabine; IV infusion of 1000 mg/m^2 of Gemcitabine given on Days 1, 8, and 15 of a 28 day cycle in cancer patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and MTD of CPI-613, when used in combination with Gemcitabine, in cancer patients.	1 Year

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare the safety and efficacy of CPI-613 Gemcitabine combination vs. Gemcitabine alone in patients with carcinoma of the pancreas.	1 year

Collaborators and Investigators

• Sponsor: Cornerstone Pharmaceuticals
• Investigators: Principal Investigator: Avi Retter, M.D., Eastchester Center for Cancer Care; Principal Investigator: Neil Senzer, M.D., Mary Crowley Cancer Research Centers

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: May 21, 2009
• First Submitted That Met QC Criteria: May 21, 2009
• First Posted (Estimate): May 22, 2009

Study Record Updates

• Last Update Posted (Actual): March 21, 2017
• Last Update Submitted That Met QC Criteria: March 19, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Cancer; Pancreatic Cancer; Phase I; Phase II; Pancreatic Carcinoma; CPI-613; Cornerstone Pharmaceuticals, Inc.; Altered Energy Metabolism Directed Compound; Carcinoma of the Pancreas
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Carcinoma; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: CL-CPI-613-004