Study of CPI-100 in Patients With Advanced Tumors

Study Overview
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Brief Summary
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This is a prospective, open-label, 2-arm, non-randomized study of CPI-100 in patients with advanced tumors. CPI-100 is administered via intravenous infusion in a 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-100 as once every two weeks (Q2W) and once every three weeks (Q3W) regimens in patients with advanced tumors Secondary Objectives: To evaluate the pharmacokinetics (PK) of CPI-100 To evaluate clinical response and resolution of symptoms after CPI-100 treatment To characterize adverse events of CPI-100 monotherapy and CPI-100 in combination with capecitabine in patients with advanced cancers Up to 5 dose levels of CPI-100 Q2W, 4 dose levels of Q3W regimen of CPI-100 monotherapy (Q3W Arm A) and 4 dose levels of Q3W regimen of CPI-100 in combination with capecitabine (Q3W Arm B) will be tested in a dose escalation study. 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-100 within 28 days (Q2W) or 42 days (Q3W): 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)

Official Title
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A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of CPI-100 Via Intravenous Infusion in Patients With Advanced Solid Tumors

Conditions
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Advanced Tumors

Intervention / Treatment
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* Drug: CPI-100
* Drug: Capecitabine


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 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 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 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3 + 3 dose escalation study design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPI-100 Monotherapy<br>Dose Escalation Groups: CPI-100 will be administered via intravenous infusion once every 2 weeks (Q2W) for up to 5 dose levels and once every 3 weeks (Q3W Arm A) for up to 4 dose levels in a 3 + 3 dose escalation study Dose Expansion Group: Maximum tolerated dose or the recommended Phase 2 dose (RP2D) from dose escalation group | Drug: CPI-100<br>* CPI-100 will be administered via intravenous infusion on Day 1 of a 14-Day cycle<br>|
| Experimental: CPI-100 Combination with Capecitabine<br>CPI-100 will be administered via intravenous infusion once every 3 weeks in combination with oral capecitabine for up to 4 dose levels in a dose escalation study (Q3W Arm B) | Drug: CPI-100<br>* CPI-100 will be administered via intravenous infusion on Day 1 of a 14-Day cycle<br>Drug: Capecitabine<br>* Capecitabine will be administered 1000 mg/m2 orally twice a day for 2 weeks followed by a 7-day rest period<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 CTCAE5 | 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 (%) | through study completion, an average of 4 months | 
| Adverse Effect | • To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE | through study completion, an average of 4 months | 
| Maximum Plasma Concentration (Cmax) | • To evaluate maximum plasma concentration (Cmax) of CPI-100 in patients tested | 8 Days | 
| Area Under the Curve (AUC) | • To evaluate area under the curve (AUC) of CPI-100 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