A Study Comparing CO-1.01 With Gemcitabine As First Line Therapy In Patients With Metastatic Pancreatic Adenocarcinoma (LEAP)

Study Overview

A Study Comparing CO-1.01 With Gemcitabine as First Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma (LEAP)

The purpose of this study is to determine whether CO-1.01 is safe and effective in the treatment of patients with metastatic pancreatic cancer and low hENT1 expression compared with gemcitabine.

Pancreatic cancer is a very serious form of cancer. The majority of patients present with unresectable disease, and the condition is often not diagnosed until the cancer is relatively advanced. The standard first-line treatment for patients with unresectable pancreatic cancer is gemcitabine monotherapy. Unfortunately many of these patients fail to derive benefit from this treatment. No clinical or molecular marker has been established to predict benefit from gemcitabine therapy, so patients are treated empirically until evidence of disease progression or worsening performance status. The potential for human equilibrative nucleoside transporter-1 (hENT1) expression to predict survival in gemcitabine-treated patients has been studied, and data suggest that patients with low levels of tumor cell hENT1 expression derive less benefit from gemcitabine treatment than patients with high levels of tumor cell hENT1 expression. These data support the hypothesis to be tested in this study that patients with pancreatic tumors expressing low levels of hENT1 will derive minimal benefit from gemcitabine, but will receive benefit from CO-1.01 (gemcitabine elaidate) which enters tumor cells in a hENT1-independent fashion.

Metastatic Pancreatic Adenocarcinoma

DRUG: CO-1.01
DRUG: Gemcitabine

CO-101-001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-05-12	Results First Submitted 2013-11-12	Last Update Submitted that met QC Criteria 2014-03-12
First Submitted that Met QC Criteria 2010-05-14	Results First Submitted that Met QC Criteria 2014-03-12	Last Update Posted (ESTIMATED) 2014-04-17
First Posted (ESTIMATED) 2010-05-17	Results First Posted 2014-04-17	Last Verified 2014-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: CO-1.01	DRUG: CO-1.01 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks
ACTIVE_COMPARATOR: gemcitabine	DRUG: Gemcitabine 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: CO-1.01

DRUG: CO-1.01

1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks

ACTIVE_COMPARATOR: gemcitabine

DRUG: Gemcitabine

1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks

Primary Outcome Measures	Measure Description	Time Frame
Overall Survival in Patients With Low High Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression		Monthly follow up after treatment discontinuation until death, up to 1.5 years.

Secondary Outcome Measures	Measure Description	Time Frame
Overall Survival in All Patients and Patients With hENT1 Expression		Monthly follow up after treatment discontinuation until death, up to 1.5 years
ORR, Duration of Response, and Progression Free Survival (PFS) in Patients With Measurable/Evaluable Disease, Using RECIST 1.1, up to 1.5 Years		Every 8 weeks
Cancer Antigen (CA)19-9 Response Rates		Every 4 weeks, up to 1.5 years
Drug Tolerability and Toxicity		Every week, up to 1.5 years
Change From Baseline in Pain Severity		Every 4 weeks, up to 1.5 years
Change From Baseline in Health Status		Every 4 weeks, up to 1.5 years
Pharmacokinetic (PK) Profile of CO-1.01 Based on Sparse Sampling		30 days after first dose

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Metastatic pancreatic ductal adenocarcinoma (i.e., Stage 4).
Histological/cytological confirmation of metastatic tissue (not primary tumor) by a central pathology laboratory (H&E stain) to ensure sufficient material is available for later hENT1 analysis.
Adjuvant chemotherapy/radiotherapy ≥ 6 months prior to randomization.
Palliative radiotherapy (if administered) ≥ 1 month prior to randomization.
CT scan ≤30 days prior to randomization
Performance Status (ECOG) 0 or 1.
Estimated life expectancy ≥ 12 weeks.
Age ≥ 18 years.
Adequate hematological and biological function.
Written consent on an Institutional Review Board/Institutional Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation.

Prior palliative chemotherapy for pancreatic cancer.
Radical pancreatic resections (e.g., Whipple procedure) are not allowed < 6 months prior to randomization. Exploratory laparotomy, palliative (e.g., bypass) surgery, or other procedures (e.g., stents) are not allowed < 14 days prior to randomization. In both cases the patient must be sufficiently recovered and stable.
Symptomatic brain metastases.
Participation in other investigational drug clinical studies ≤ 30 days prior to randomization.
Concomitant treatment with prohibited medications.
History of allergy to gemcitabine or eggs.
Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, symptomatic pulmonary embolism).
Any disorder that would hamper protocol compliance.
Prior nonpancreatic malignancy treated with chemotherapy. Prior malignancies treated with surgery or radiotherapy alone must be in remission ≥ 3 years. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic skin cancer.
Females who are pregnant or breastfeeding.
Refusal to use adequate contraception for fertile patients (females and males during the study and for 6 months after the last study treatment). Adequate forms of contraception are double-barrier methods (condoms or diaphragm with spermicidal jelly or foam); oral, depot, or injectable contraceptives; intrauterine devices; tubal ligation.
Any other reason the investigator considers the patient should not participate in the study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

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General Publications

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