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.
Open-Label Single-Arm Design: This is an open-label study, and investigators and subjects are not blinded to the treatment. Also, the assignment of patients will not be randomized, since this is a single-arm study. Treatment with CPI-613: A treatment cycle is 4 weeks, with CPI-613 given on Days 1 and 4 of the first 3 weeks. Dose and Sample Size: The dose of CPI-613 is 3,000 mg/m2. This is Maximum Tolerated Dose (MTD) determined from the Phase I dose-escalated trial, Study# CL-CPI-613-009 (conducted in patients with hematologic malignancies under IND 107,800). This dose has also been found to be well tolerated in another Phase I dose-escalated trial, Study# CL-CPI-613-002 (conducted in patients with solid tumor under IND 74,530). There will be 20 evaluable patients with each tumor type. Once there are 20 evaluable patients with a particular tumor type has been treated with at least 1 cycle, no patients of the same tumor type will be accrued. Dosing Delay and Dose Modification of CPI-613 in the Event of Adverse Events: For adverse events unrelated to serum creatinine elevation or reduction in renal function but are possibly related to CPI-613, the occurrence of Grade 1 toxicity does not generally require dose modification for subsequent doses for that patient. However, if Grade 2 toxicity (other than alopecia and nausea) probably related to CPI-613 develops, treatment is to be withheld and can resume only after the Grade 2 toxicity has been reduced to Grade 1 or below, and the dose level for subsequent doses for that patient will be reduced by 25% of the dose at which such Grade 2 toxicity occurs. Grade 2 alopecia and nausea do not require withholding treatment or dose reduction. If Grade 3 or 4 toxicity probably related to CPI-613 develops, dosing of CPI-613 of that patient will be withheld and the patient shall be monitored for recovery from, and reversibility of, such Grade 3 or 4 toxicity. To resume treatment with CPI-613 for a patient who has had CPI-613-related Grade 3 or 4 toxicity, the Grade 3 or 4 toxicity must be reduced to Grade 1 or below, and the dose level for subsequent doses for that patient will be reduced to 50% of the dose at which such Grade 3 or 4 toxicity occurs. For adverse events related to creatinine elevation or reduction in renal function that are possibly related to CPI-613, dosing of the patient will be withheld even if the severity level is Grade 1 or above. Treatment can resume only after the toxicity has been reduced to Grade 0. The dose level for subsequent doses for that patient will be reduced by 15% if the severity level is of Grade 1, by 25% for Grade 2 toxicity, and by 50% for Grade 3 or 4 toxicity. Furthermore, if the toxicity possibly related to CPI-613 is acute renal failure and the severity level is Grade 3 or 4, further patient enrollment will be temporarily suspended in order to enable assessment of the following aspects of the trial and implementation of corrective measures or protocol amendment, and if necessary: * compliance of the study sites and investigators to the study protocol * evaluation of the appropriateness of the procedures for monitoring renal function
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
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.
Eastchester Center for Cancer Care
The Bronx, New York, United States
Overall Survival (OS)
Time frame: Monitored until participants pass away, for an expected average of 6 months.
Progression-Free Survival (PFS)
Time frame: Monitored during treatment with CPI-613 and until participants passed away, which will be an expected average of 6 months.
Safety
Safety assessment will be based on clinical signs, vital signs, blood work, adverse events (AEs), serious adverse events (SAEs), etc.
Time frame: 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
Time frame: Monitored at the end of every 4-week treatment cycle during treatment with CPI-613, for an expected average of 20 weeks.
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