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

Lung Cancer Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01641575
• Other study ID #: CO-101-011
• Status: Terminated
• Phase: Phase 1
• First received: July 9, 2012
• Last updated: March 8, 2014
• Start date: July 2012
• Est. completion date: June 2013

Study information

• Verified date: March 2014
• Source: Clovis Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: June 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non-small-cell Lung Cancer
• Solid Tumor

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	The Beatson West	Glasgow	Scotland
United Kingdom	University College London Cancer Institute	London
United States	Tennessee Oncology	Nashville	Tennessee
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Clovis Oncology, Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Primary	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	Yes
Primary	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.	Yes
Primary	ECG Abnormalities (Part 2)		Screening (within 2 weeks of Cycle 1 Day 1)	Yes
Secondary	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	No
Secondary	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	Yes
Secondary	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.	Yes
Secondary	ECG abnormalities (Part 1)		Screening (within 2 weeks of Cycle 1 Day 1)	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Tumor hENT1 expression (Part 2)		Screening (within 2 weeks of Cycle 1 Day 1)	No