Safety and Effectiveness Study of CPI-613 and/or Gemcitabine to Treat Metastatic Pancreatic Cancer

Metastatic Pancreatic Adenocarcinoma Clinical Trial

Official title:

A Phase II Open-Label Clinical Trial of CPI-613 Given Alone, or in Combination With Gemcitabine, in Patients With Metastatic Pancreatic Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01830322
• Other study ID #: CL-CPI-613-024
• Status: Withdrawn
• Phase: Phase 2
• First received: April 3, 2013
• Last updated: August 13, 2013
• Start date: January 2014
• Est. completion date: December 2018

Study information

• Verified date: August 2013
• Source: Cornerstone Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This Phase II study is conducted to assess the safety and efficacy of CPI-613 in patients with metastatic pancreatic cancer. The primary outcome measure is Overall Survival (OS). The secondary outcome measures are: changes in CA 19-9, Quality of Life (QOL), Progression-Free Survival (PFS), and safety.

Description:

Data from dose-escalated Phase I trials indicate that CPI-613 is safe and effective against metastatic pancreatic cancer (Lee et al. 2012; Retter et al. 2012). Accordingly, this Phase II trial is conducted to assess the safety and efficacy of CPI-613 in patients with metastatic pancreatic cancer.

Primary Outcome Measure:

• Overall Survival (OS)

Secondary Outcome Measures:

• Changes in CA 19-9

• Quality of Life (QOL) assessment

• Progression-Free Survival (PFS)

• Safety

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Histologically and cytologically confirmed, measurable metastatic pancreatic adenocarcinoma

• Eastern Cooperative Oncology Group (ECOG) performance status being 0-2

• Expected survival >2 months

• 18 years of age or older 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. (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, unless documentation of infertility exists.

• At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. 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"), unless treated with anticoagulants.

• No evidence of active infection and no serious infection within the past month; no systemic fungal, bacterial, viral or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment.

• Consent to participating the study by signed informed consent form

Exclusion Criteria:

• Serious medical illness that would potentially increase patients' risk for toxicity

• Any active uncontrolled bleeding or patients with a bleeding diathesis (e.g., active peptic ulcer disease)

• Patients with active central nervous system (CNS) or epidural tumor

• Lactating females (Note: Lactating females are excluded because the effects of CPI-613 on a nursing child are unknown)

• Life expectancy less than 2 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. Also patients with a history of myocardial infarction that is <1 year prior to registration, or patients with previous congestive heart failure (<1 year prior to registration) requiring pharmacologic support or with Left Ventricular Ejection Fraction <50%).

• 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).

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Adenocarcinoma
• Pancreatic Neoplasms

Intervention

Drug:
• CPI-613
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 approximate maximum tolerated dosing [MTD]), via a central venous catheter with D5W running at a rate of about 125-150 mL/hr.
• Gemcitabine

• Any non-gemcitabine chemotherapies or best supportive care

Locations

Country	Name	City	State
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	Temple Vasicek Cancer Treatment Center	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Cornerstone Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)		Monitored until participants pass away, for an expected average of 6 months.	Yes
Secondary	Changes in CA 19-9	CA 19-9 is monitored through blood work =2 weeks before treatment and after every third cycle (12 weeks) of treatment while on-study. CA 19-9 is a pancreatic tumor biomarker and a decline in CA 19-9 during and after therapy may be a marker of treatment efficacy.	Monitored within 2-weeks before treatment, and every 3-cycles (months) during treatment	No
Secondary	Quality of Life (QOL)	QOL will be assessed as described by Aaronson NK, et al. 1993. It assesses how the various treatments and the disease affect the daily living abilities of the patient.	Monitored before, during, and 1-week after treatment with CPI-613, for an expected average of 20 weeks.	No
Secondary	Progression-Free Survival (PFS)		Monitored during treatment with CPI-613 and until participants passed away, which will be an expected average of 6 months.	No
Secondary	Safety	Safety assessment will be based on clinical signs, vital signs, blood work, adverse events (AEs), serious adverse events (SAEs), etc.	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.	Yes