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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of CPI-300 Via Intravenous Infusion in Patients With Advanced Solid Tumors

Conditions
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Advanced Tumors

Intervention / Treatment
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* Drug: CPI-300


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: accelerated titration method followed by a conventional 3 + 3 dose escalation study design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPI-300<br>Dose Escalation Group: CPI-300 will be administered via intravenous infusion once every 2 weeks for up to 6 dose levels using an accelerated titration method followed by a conventional 3 + 3 study design | Drug: CPI-300<br>* CPI-300 will be administered via intravenous infusion on Day 1 of a 14-Day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | To determine the maximum tolerated dose (MTD), which is defined as the highest dose level at which number of patients reporting a dose limiting toxicity (DLT) is less than or equal to 33% | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit | To assess clinical benefit by response rate and resolution of symptoms, which will be reported as response rate (%) | 28 Days and additional CPI-300 treatments till disease progression or intolerability | 
| Adverse Effect | To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE | 28 Days and additional CPI-300 treatment till disease progression or intolerability | 
| Maximum Plasma Concentration (Cmax) | To evaluate maximum plasma concentration (Cmax) of CPI-300 in patients tested | 8 Days | 
| Area Under the Curve (AUC) | To evaluate area under the curve (AUC) of CPI-300 in patients tested | 8 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intravenous Infusion