A Open Label Phase I/II Clinical Trial to Evaluate CPI-613 in Patients With Advanced Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Cornerstone Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00741403
First received: August 25, 2008
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

An open label, dose-escalation study to evaluate safety, tolerability, maximum tolerated dose (MTD), efficacy, and pharmacokinetics (PKs) of CPI-613 given twice weekly for three consecutive weeks in cancer patients

The objectives of this study are:

  • To determine the safety and MTD of CPI-613 when administered 2x weekly for 3 consecutive weeks.
  • To determine pharmacokinetics of CPI-613 following intravenous (IV) administration.
  • To observe the anti-tumor effects of CPI-613, if any occur.

Condition Intervention Phase
Advanced Cancer
Metastatic Cancer
Lymphoma
Solid Tumors
Advanced Malignancies
Drug: CPI-613
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Dose-Escalation Study to Evaluate Safety, Tolerability, Maximum Tolerated Dose (MTD), Efficacy, and Pharmacokinetics (PKs) of CPI-613 Given Twice Weekly for Three Consecutive Weeks in Cancer Patients

Resource links provided by NLM:


Further study details as provided by Cornerstone Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • To evaluate the safety, tolerability, maximum tolerated dose (MTD), and efficacy pharmacokinetics of CPI-613 given twice weekly for three consecutive weeks in cancer patients [ Time Frame: October 2010 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate pharmacokinetics, toxicity profile, biological activity, and anti-tumor activity of CPI-613 given twice weekly for three consecutive weeks in cancer patients [ Time Frame: Octoboer 2010 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: August 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
IV Infusion of CPI-613 on Days 1,4,8,11,15,18 of 28 day cycle in patients with advanced malignancies
Drug: CPI-613
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

  Eligibility

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

Inclusion Criteria:

  • Patients must have advanced and/or metastatic, histologically or cytologically documented solid tumors and lymphomas, for whom there is no available therapy shown to provide clinical benefit.
  • Karnofsky Performance Status (KPS) of >70%.
  • Must be ≥18 years of age.
  • Expected survival >3 months.
  • 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), and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation. (Note: Pregnant patients are excluded because the effects of CPI-613 on a fetus are unknown.)
  • Fertile men must practice effective contraceptive methods during the study period, unless documentation of infertility exists.
  • Mentally competent, ability to understand and willingness to sign the informed consent form.
  • No radiotherapy, treatment with cytotoxic agents (except CPI-613), or treatment with biologic agents within the 3 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 ≥100,000 cells/mm^3 or ≥100 bil/L; absolute neutrophil count [ANC] ≥1500 cells/mm^3 or ≥1.5 bil/L; and hemoglobin (Hgb) ≥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 ≤1.5x UNL).
    • Adequate renal function (serum creatinine ≤2.0 mg/dL or 177 µmol/L).
    • Adequate coagulation (International Normalized Ratio or INR must be ≤1.25).

Exclusion Criteria:

  • Serious medical illness, such as significant cardiac disease (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 because the potential of excretion of CPI-613 into breast milk. (Note: Lactating females are excluded because the effects of CPI-613 on a nursing child are unknown.)
  • Fertile men unwilling to practice contraceptive methods during the study period.
  • 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.
  • Dyspnea with minimal to moderate exertion. Patients with large and recurrent pleural, or peritoneal effusions requiring frequent drainage (e.g. weekly). Patients with any amount of clinically significant pericardial effusion.
  • 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 3 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., clinically significant heart failure, hypokalemia, family history of Long QT Syndrome).
  • Troponin I above institution limit of normal or Left Ventricular Ejection Fraction (LVEF) below 35%.
  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: NCT00741403

Locations
United States, Arizona
Pivotal Research Centers
Peoria, Arizona, United States, 85381
United States, New York
Eastchester Center for Cancer Care
Bronx, New York, United States, 10469
United States, Texas
Mary Crowley Cancer Research Centers
Dallas, Texas, United States, 75201
Canada, British Columbia
British Columbia Cancer Agency
Vancouver, British Columbia, Canada
Sponsors and Collaborators
Cornerstone Pharmaceuticals, Inc.
Investigators
Principal Investigator: Karen Gelmon, M.D. British Columbia Cancer Agency
Principal Investigator: Avi Retter, M.D. Eastchester Center for Cancer Care
Principal Investigator: Divis K Khaira, M.D. Pivotal Research Centers
Principal Investigator: Senzer Neil, M.D. Mary Crowley Cancer Research Centers
  More Information

No publications provided

Responsible Party: Cornerstone Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00741403     History of Changes
Other Study ID Numbers: CL-CPI-613-002
Study First Received: August 25, 2008
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Cornerstone Pharmaceuticals, Inc.:
Phase I
Phase II
malignancies
refractory
relapsed

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on October 21, 2014