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

A Phase I Open-Label, Ascending Dose Cohort Study of Gemcitabine Elaidate and Cisplatin in Patients With Advanced Solid Tumors Followed by an Expanded Cohort of Patients With Stage IIIb/IV NSCLC.

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).

Study Overview

• Status: Terminated
• Conditions: Lung Cancer; Solid Tumor; Non-small-cell Lung Cancer
• Intervention / Treatment: Drug: CO-1.01 and Cisplatin

Detailed Description

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
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W1T 4TJ
    • University College London Cancer Institute
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • The Beatson West
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CO-1.01 and Cisplatin	Drug: CO-1.01 and Cisplatin; CO-1.01 administered over 30 minutes followed by 75 mg/ml Cisplatin over 2 hours (both intravenous) on C1D1. CO-1.01 administered intravenously over 30 minutes on C1D8.; Other Names: Gemcitabine elaidate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose limiting toxicities (DLT)(Part 1)	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)	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)	For Cycle 1: Day 1, Day 8, Day 15. For subsequent cycles: Day 1, Day 8.
ECG Abnormalities (Part 2)	Screening (within 2 weeks of Cycle 1 Day 1)

Secondary Outcome Measures

Outcome Measure	Time Frame
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)	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)	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)	For Cycle 1: Day 1, Day 8, Day 15. For subsequent cycles: Day 1, Day 8.
ECG abnormalities (Part 1)	Screening (within 2 weeks of Cycle 1 Day 1)
Overall response rate (ORR)(Part 2)	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)	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)	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)	Screening (within 2 weeks of Cycle 1 Day 1)

Collaborators and Investigators

• Sponsor: Clovis Oncology, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: July 9, 2012
• First Submitted That Met QC Criteria: July 16, 2012
• First Posted (Estimate): July 17, 2012

Study Record Updates

• Last Update Posted (Estimate): March 11, 2014
• Last Update Submitted That Met QC Criteria: March 8, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: NSCLC; lung cancer; solid tumor; non-small-cell lung cancer; hENT1; CO-1.01; CO-101; gemcitabine elaidate; nucleoside equilibrative transporter
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: CO-101-011