Phase 2 Safety, Tolerability and Efficacy Study of CPI-613 in Cancer Patients

NCT01832857 | Terminated Phase 2

• 1 other identifier: CL-CPI-613-023
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase II study is conducted to assess the safety and efficacy of CPI-613 in patients with advanced and/or metastatic solid tumors for whom there there is no available therapy to provide clinical benefit or for those who have refused further standard therapy. The primary outcome measure is Overall Survival (OS). The secondary outcome measures are: Response Rate (RR), Progression-Free Survival (PFS), and safety.

Conditions

Cancer

Keywords

metastatic; advanced; solid tumor; cancer; colon cancer; hepatocellular carcinoma; breast cancer; lung cancer; gastric cancer; esophageal cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Monitored until participants pass away, for an expected average of 6 months.

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Monitored during treatment with CPI-613 and until participants passed away, which will be an expected average of 6 months.

• Safety

  Monitored just before study treatment, and during study treatment at the end of every 4-week treatment cycle, for an expected average of 20 weeks.

• Response Rate

  Monitored at the end of every 4-week treatment cycle during treatment with CPI-613, for an expected average of 20 weeks.

Study Arms (1)

CPI-613 Alone

EXPERIMENTAL

This arm is for patients that have failed, or are not eligible for, all available therapies. CPI-613 drug product, provided in concentrated form at 50 mg/mL, must be diluted with D5W prior to administration. CPI-613 is to be infused intravenously (IV) via a central venous catheter. CPI-613 will be given 2x weekly, administered on Days 1 and 4 of each of the 3 treatment weeks, followed by a week of rest. The dose of CPI-613 will be 3,000 mg/m2 infused IV over 2 hours (this is the maximum tolerated dosing \[MTD\]), via a central venous catheter with D5W running at a rate of about 125-150 mL/hr.

Drug: CPI-613

Interventions

CPI-613 DRUG

CPI-613 drug product, provided in concentrated form at 50 mg/mL, must be diluted with D5W prior to administration. CPI-613 is to be infused intravenously (IV) via a central venous catheter. CPI-613 will be given 2x weekly, administered on Days 1 and 4 of each of the 3 treatment weeks, followed by a week of rest. The dose of CPI-613 will be 3,000 mg/m2 infused IV over 2 hours (this is the maximum tolerated dosing \[MTD\]), via a central venous catheter with D5W running at a rate of about 125-150 mL/hr.

Also known as: 6,8-bis-benzylsulfanyloctanoic acid, 6,8-bis(benzylthio)octanoic acid, 6,8-bis-benzylsulfonyloctanoic acid, Bylantra (tentative)

CPI-613 Alone

Eligibility Criteria

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

You may qualify if:

• Patients must have advanced and/or metastatic, histologically or cytologically documented solid tumors, for whom there is no available therapy shown to provide clinical benefit or for those who have refused further standard therapy
• Eastern Cooperative Oncology Group (ECOG) performance status being 0-2
• Expected survival \>3 months
• years of age or older of both genders
• Women of child-bearing potential 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
• Mentally competent, with an 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 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 any anti-cancer 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/mm3 or ≥3.5 bil/L; platelet count ≥150,000 cells/mm3 or ≥150 bil/L; absolute neutrophil count \[ANC\] ≥1500 cells/mm3 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, and blood urea nitrogen \[BUN\] ≤25 mg/dL).
• Adequate coagulation ("International Normalized Ratio or INR must be ≤1.5")

You may not qualify if:

• Serious medical illness
• Any active uncontrolled bleeding or patients with a bleeding diathesis
• Patients with active central nervous system (CNS) or epidural tumor
• Pregnant women, or women of child-bearing potential not using reliable means of contraception
• Lactating females
• Fertile men unwilling to practice contraceptive methods during the study period
• Life expectancy less than 3 months
• Unwilling or unable to follow protocol requirements
• Dyspnea with minimal to moderate exertion, or patients with pleural, pericardial, or peritoneal effusions
• Active heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction, arrhythmias requiring medication, or symptomatic congestive heart failure.
• A marked baseline prolongation of QT/QTc interval; a history of additional risk factors for torsade de pointes.
• Requirement for immediate palliative treatment of any kind including surgery
• Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
• Albumin \<2.5 g/dL or \<25 g/L
• Evidence of active infection, or serious infection, with the past month

Sponsors & Collaborators

• Cornerstone Pharmaceuticals: lead

Study Sites (1)

Eastchester Center for Cancer Care

The Bronx, New York, 10469, United States

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Carcinoma, Hepatocellular; Breast Neoplasms; Lung Neoplasms; Stomach Neoplasms; Esophageal Neoplasms

Interventions

devimistat

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Study Officials

• King C Lee, Ph.D.

  Cornerstone Pharmaceuticals

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 16, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: December 29, 2016

Record last verified: 2016-12

Locations

US (1)