Study of CPI-200 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-200 in patients with advanced tumors. CPI-200 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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Primary Objectives: • To determine the safety, tolerability and maximum tolerated dose (MTD) of CPI-200 in patients with advanced tumors Secondary Objectives: To evaluate the pharmacokinetics (PK) of CPI-200 To evaluate clinical response and resolution of symptoms after CPI-200 treatment To characterize adverse events of CPI-200 in patients with advanced cancers Up to 7 dose levels of CPI-200 will be tested using an accelerated titration method followed by a conventional 3 + 3 dose escalation study design. 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-200 within 21 days: All Grade 4 or greater adverse events as determined by CTCAEv5 criteria, excluding toxicities clearly related to disease progression or inter-current illness Any Grade 3 or greater non-hematologic, non-dermatologic toxicity with the exception of Grade 3 nausea, vomiting or diarrhea if lasting less than 72 hours, alopecia, or Grade 3 fatigue if lasting less than 7 days as determined by CTCAEv5 criteria Grade 3 thrombocytopenia in the presence of bleeding Grade 3 or greater febrile neutropenia Any hematologic or non-hematologic adverse events or abnormal laboratory value(s) related to CPI-200 that result(s) in permanent study discontinuation of study treatment

Official Title
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A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of CPI-200 Via Intravenous Infusion in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: CPI-200


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Males and females 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 a life expectancy of at least 12 weeks (in the opinion of the investigator) Have adequate bone marrow reserve, liver and renal function Be reasonably recovered from preceding major surgery and 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 3 months after the last day of treatment Exclusion Criteria: Have peripheral sensory neuropathy of Grade 2 or greater at screening Have known hypersensitivity to chemotherapeutic agents Have 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: unstable angina, myocardial infarction or cerebrovascular accident, transient ischemic attack, cardiac failure with known ejection fraction less than 40% 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: Sequential Assignment
Interventional Model Description: Accelerated titration method followed by a conventional 3 + 3 study design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPI-200<br>Dose Escalation Group: CPI-200 will be administered via intravenous infusion once every 3 weeks for up to 7 dose levels using an accelerated titration method followed by a conventional 3 + 3 study design Dose Expansion Group: Maximum tolerated dose or the recommended Phase 2 dose (RP2D) from dose escalation group | Drug: CPI-200<br>* CPI-200 will be administered via intravenous infusion on Day 1 of a 21-Day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | • To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy as assessed by CTCAE | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Clinical Benefit | • To assess clinical benefit by response rate and resolution of symptoms, which will be reported as response rate (%) of participants | through study completion, an average of 4 months | 
| Rate of Adverse Effect | • To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE, which will be reported as % of participants | through study completion, an average of 4 months | 
| Maximum Plasma Concentration (Cmax) | • To evaluate maximum plasma concentration (Cmax) of CPI-200 in patients tested | 8 Days | 
| Area Under the Curve (AUC) | • To evaluate area under the curve (AUC) of CPI-200 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, Phase 1, CPI-200