Phase I Study of CPI-300 in Patients With Advanced Tumors

This is a prospective, open-label, single arm, non-randomized study of CPI-300 in patients with advanced tumors. CPI-300 is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD).

Up to 6 dose levels of CPI-300 will be tested. MTD will be defined as the dose associated with a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from the intravenous injection of CPI-300 within 28 days:

* Grade 4 or greater treatment related adverse events
* Any Grade 3 or greater treatment related non-hematologic, non-dermatologic toxicity (including nausea, vomiting or diarrhea lasting more than 72 hours)

Blood samples will be drawn to determine drug blood concentrations for pharmacokinetic assessment.

Eligibility Criteria:
Inclusion Criteria:

* Have a histologically or cytologically confirmed diagnosis of advanced solid tumor
* Have advanced or metastatic disease refractory to standard curative or palliative therapy or contraindication to standard therapy
* Have an ECOG performance status of 0-1
* Have adequate bone marrow reserve, liver and renal function
* Be reasonably recovered from preceding major surgery or no major surgery within 4 weeks prior to the start of Day 1 treatment
* Have a negative pregnancy test for females with child bearing age at screening and should not be breast feeding
* Be willing to abstain from sexual activity or practice physical barrier contraception from study entry to 6 months after the last day of treatment

Exclusion Criteria:

* Have peripheral neuropathy of Grade 3 or Grade 4 at screening
* Have peripheral sensory neuropathy of Grade 2 or greater at screening
* Have an interval from previous neurotoxic drugs less than 3 months unless reasonably recovered from all grades of neurotoxicity to grade 1 or lower as judged by the investigator
* Have known hypersensitivity to chemotherapeutic agents
* Have chronic diarrhea
* Have a history of thrombocytopenia with complications including hemorrhage or bleeding \> Grade 2 that required medical intervention or any hemolytic condition or coagulation disorders that would make participation unsafe
* Have unresolved toxicity from previous treatment or previous investigational agents; excluding alopecia
* Received investigational agents or systemic anticancer agents (other than neurotoxic compounds) within 5 half lives or 28 days, whichever is shorter, prior to Day 1 of treatment
* Have signs or symptoms of end organ failure, major chronic illnesses other than cancer, or any severe concomitant conditions
* Have experienced any of the following within the 6-month period prior to screening: angina pectoris, coronary artery disease or cerebrovascular accident, transient ischemic attack, cardiac failure with known ejection fraction less than 40%, or cardiac arrhythmia requiring medical therapy
* Have other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that would make the patient inappropriate for enrollment in this study
* Is pregnant or breast-feeding