Back to resultsA Dose Ascending Study of Gemcitabine Elaidate (CO-101) in Combination With Cisplatin
Primary Purpose
Solid Tumor, Non-small-cell Lung Cancer, Lung Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CO-1.01 and Cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumor focused on measuring CO-1.01, CO-101, gemcitabine elaidate, hENT1, nucleoside equilibrative transporter, solid tumor, non-small-cell lung cancer, NSCLC, lung cancer
Eligibility Criteria
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
Sites / Locations
- Florida Cancer Specialists
- Tennessee Oncology
- The Beatson West
- University College London Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CO-1.01 and Cisplatin
Arm Description
Outcomes
Primary Outcome Measures
Dose limiting toxicities (DLT)(Part 1)
Adverse events (Description of event in medical terminology, Intensity, Relationship to drug, Outcome, and/or Follow up )(Part 2)
Clinical Laboratory Abnormalities (ANC, Platelets, Hemoglobin, AST/ALT, Bilirubin, Creatinine clearance)(Part 2)
ECG Abnormalities (Part 2)
Secondary Outcome Measures
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)
Adverse events (Description of event in medical terminology, Intensity, Relationship to drug, Outcome, and/or Follow up )( (Part 1)
Clinical Laboratory Abnormalities (ANC, Platelets, Hemoglobin, AST/ALT, Bilirubin, Creatinine clearance)(Part 1)
ECG abnormalities (Part 1)
Overall response rate (ORR)(Part 2)
Duration of response (Part 2)
Progression-free survival (PFS)(Part 2)
Tumor hENT1 expression (Part 2)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01641575
Brief Title
A Dose Ascending Study of Gemcitabine Elaidate (CO-101) in Combination With Cisplatin
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Terminated
Why Stopped
Registrational study did not meet endpoint so entire program (including CO-101-011) was terminated.
Study Start Date
July 2012 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Clovis Oncology, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Non-small-cell Lung Cancer, Lung Cancer
Keywords
CO-1.01, CO-101, gemcitabine elaidate, hENT1, nucleoside equilibrative transporter, solid tumor, non-small-cell lung cancer, NSCLC, lung cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CO-1.01 and Cisplatin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CO-1.01 and Cisplatin
Other Intervention Name(s)
Gemcitabine elaidate
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Title
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
Title
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.
Title
ECG Abnormalities (Part 2)
Time Frame
Screening (within 2 weeks of Cycle 1 Day 1)
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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.
Title
ECG abnormalities (Part 1)
Time Frame
Screening (within 2 weeks of Cycle 1 Day 1)
Title
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
Title
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
Title
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
Title
Tumor hENT1 expression (Part 2)
Time Frame
Screening (within 2 weeks of Cycle 1 Day 1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Florida Cancer Specialists
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
The Beatson West
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
University College London Cancer Institute
City
London
ZIP/Postal Code
W1T 4TJ
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Dose Ascending Study of Gemcitabine Elaidate (CO-101) in Combination With Cisplatin
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