A Dose Ascending Study of Gemcitabine Elaidate (CO-101) in Combination With Cisplatin

Phase 1TerminatedNCT01641575

Clovis Oncology, Inc.8 enrolled

Overview

The purpose of the first part of the study is to evaluate the safety, tolerability, and pharmacokinetics of ascending doses of gemcitabine elaidate in combination with cisplatin given to patients with advanced solid tumors, and to select a dose for further evaluation in the second part of the study. The purpose of the second part of the study is to determine the safety, tolerability, and exploratory clinical activity of gemcitabine elaidate in combination with cisplatin given to patients with Stage IIIb/IV non-small-cell lung cancer (NSCLC).

The chemotherapy doublet of cisplatin and gemcitabine is an effective regimen for solid tumors including NSCLC. Entry of gemcitabine into tumor cells has been shown to be dependent on specific membrane transporter proteins, particularly human equilibrative nucleoside transporter 1 (hENT1). Patients with low tumor hENT-1 expression may respond poorly to gemcitabine-containing chemotherapy. Gemcitabine elaidate (CO-1.01) is a fatty acid derivative of gemcitabine, and can enter cells in the absence of hENT1. CO-1.01 therefore, may overcome hENT1-mediated resistance to gemcitabine. CO-1.01 is currently being evaluated as a single agent in a pivotal randomized trial in 360 patients with metastatic pancreatic adenocarcinoma. The appropriate dose of CO-1.01 when given as part of combination therapy with a platinum agent such as cisplatin is not yet known. The objectives of this study are to: * determine the maximum tolerated dose (MTD) of CO-1.01 when combined with a fixed dose of cisplatin in patients with solid tumors * select a recommended dose (RD) for dose expansion in patients with Stage IIIb/IV NSCLC * explore clinical activity of CO-1.01 in patients with Stage IIIb/IV NSCLC

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Understand and sign institutional review board/independent ethics committee-approved informed consent form (ICF) prior to any study-specific evaluation * Life expectancy of at least 3 months * ECOG performance status of 0 to 1 * ≥ 18 years at the time ICF is signed * Adequate hematological and biological function * Histologically or cytologically confirmed solid tumor malignancy (Part 1 only) * Histologically or cytologically confirmed stage IIIb/IV NSCLC (Part 2 only) Exclusion Criteria: * Symptomatic central nervous system metastases * Concomitant treatment with prohibited medications, e.g. other chemotherapy, radiation, hormonal treatment (excepting corticosteroids), or immunotherapy ≤ 14 days prior to CO-1.01 treatment * Treatment with a previous regimen of CO-1.01 * Participation in another therapeutic clinical study within 14 days of enrollment or during this clinical study * Surgical procedures ≤ 14 days prior to CO-1.01 administration * History of allergy to gemcitabine, gemcitabine elaidate or eggs * Known allergic/hypersensitivity reaction to cisplatin, other platinum agent, or platinum containing compounds * Peripheral neuropathy ≥ Grade 1 * Females who are pregnant or breastfeeding * Refusal to use adequate contraception for fertile patients * Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study * Any other reason the investigator considers the patient should not participate in the study

Locations (4)

Florida Cancer Specialists

Sarasota, Florida, United States

Tennessee Oncology

Nashville, Tennessee, United States

University College London Cancer Institute

London, London, United Kingdom

The Beatson West

Glasgow, Scotland, United Kingdom

Outcomes

Primary Outcomes

Dose limiting toxicities (DLT)(Part 1)

Time frame: From time taking first dose of CO-1.01 (Cycle 1 Day 1) through last day of Cycle 1 (Cycle 1 Day 21), an expected average of 6 weeks.

Adverse events (Description of event in medical terminology, Intensity, Relationship to drug, Outcome, and/or Follow up )(Part 2)

Time frame: From time of signing informed consent form through 28 days after last dose of CO-1.01, an expected average of 7 weeks

Clinical Laboratory Abnormalities (ANC, Platelets, Hemoglobin, AST/ALT, Bilirubin, Creatinine clearance)(Part 2)

Time frame: For Cycle 1: Day 1, Day 8, Day 15. For subsequent cycles: Day 1, Day 8.

ECG Abnormalities (Part 2)

Time frame: Screening (within 2 weeks of Cycle 1 Day 1)

Secondary Outcomes

PK parameters for CO-1.01 and its metabolites in plasma and urine (AUC, Cmax, Tmax, half life, kel, Vss, Cl, and MRT) (Part 1)

Time frame: Cycle 1: Day 1, Day 8

Adverse events (Description of event in medical terminology, Intensity, Relationship to drug, Outcome, and/or Follow up )( (Part 1)

Time frame: From time of signing informed consent form through 28 days after last dose of CO-1.01, an expected average of 7 weeks

Clinical Laboratory Abnormalities (ANC, Platelets, Hemoglobin, AST/ALT, Bilirubin, Creatinine clearance)(Part 1)

Time frame: For Cycle 1: Day 1, Day 8, Day 15. For subsequent cycles: Day 1, Day 8.

ECG abnormalities (Part 1)

Time frame: Screening (within 2 weeks of Cycle 1 Day 1)

Overall response rate (ORR)(Part 2)

Time frame: Screening (within 2 weeks of Cycle 1 Day 1); prior to start of cycles 3,5,7; every 3 cycles thereafter

Duration of response (Part 2)

Time frame: Screening (within 2 weeks of Cycle 1 Day 1); prior to start of cycles 3,5,7; every 3 cycles thereafter

Progression-free survival (PFS)(Part 2)

Time frame: Screening (within 2 weeks of Cycle 1 Day 1); prior to start of cycles 3,5,7; every 3 cycles thereafter

Tumor hENT1 expression (Part 2)

Time frame: Screening (within 2 weeks of Cycle 1 Day 1)

A Dose Ascending Study of Gemcitabine Elaidate (CO-101) in Combination With Cisplatin

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes