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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01124786
Recruitment Status : Completed
First Posted : May 17, 2010
Results First Posted : April 17, 2014
Last Update Posted : April 17, 2014
Information provided by (Responsible Party):
Clovis Oncology, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Drug: CO-1.01 Drug: Gemcitabine Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 367 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Open-Label, Multicenter Study Comparing CO-1.01 With Gemcitabine as First-Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma
Study Start Date : May 2010
Actual Primary Completion Date : November 2012
Actual Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

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 :
  1. Overall Survival in Patients With Low High Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression [ Time Frame: Monthly follow up after treatment discontinuation until death, up to 1.5 years. ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01124786

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Sponsors and Collaborators
Clovis Oncology, Inc.
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Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01124786    
Other Study ID Numbers: CO-101-001
First Posted: May 17, 2010    Key Record Dates
Results First Posted: April 17, 2014
Last Update Posted: April 17, 2014
Last Verified: March 2014
Keywords provided by Clovis Oncology, Inc.:
human equilibrative nucleoside transporter-1 (hENT1)
Stage 4
Stage IV
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents