Study of CPI-100 in Patients With Advanced Tumors

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

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).

Study Overview

• Status: Completed
• Conditions: Advanced Tumors
• Intervention / Treatment: Drug: CPI-100; Drug: Capecitabine

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • South Texas Accelerated Research Therapeutics
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPI-100 Monotherapy; 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; CPI-100 will be administered via intravenous infusion on Day 1 of a 14-Day cycle
Experimental: CPI-100 Combination with Capecitabine; 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; CPI-100 will be administered via intravenous infusion on Day 1 of a 14-Day cycle; Drug: Capecitabine; Capecitabine will be administered 1000 mg/m2 orally twice a day for 2 weeks followed by a 7-day rest period

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Coordination Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Actual): June 21, 2022
• Study Completion (Actual): June 21, 2022

Study Registration Dates

• First Submitted: December 17, 2018
• First Submitted That Met QC Criteria: December 18, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Intravenous infusion
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: CPI-CL18-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data will not be shared due to confidentiality agreements

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No