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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01124786
First received: May 12, 2010
Last updated: March 12, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Metastatic Pancreatic Adenocarcinoma
Drug: CO-1.01
Drug: Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Cancer Antigen (CA)19-9 Response Rates [ Time Frame: Every 4 weeks, up to 1.5 years ] [ Designated as safety issue: No ]
  • Drug Tolerability and Toxicity [ Time Frame: Every week, up to 1.5 years ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Pain Severity [ Time Frame: Every 4 weeks, up to 1.5 years ] [ Designated as safety issue: No ]
  • Change From Baseline in Health Status [ Time Frame: Every 4 weeks, up to 1.5 years ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) Profile of CO-1.01 Based on Sparse Sampling [ Time Frame: 30 days after first dose ] [ Designated as safety issue: No ]

Enrollment: 367
Study Start Date: May 2010
Study Completion Date: June 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01124786

  Show 95 Study Locations
Sponsors and Collaborators
Clovis Oncology, Inc.
  More Information

No publications provided

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01124786     History of Changes
Other Study ID Numbers: CO-101-001
Study First Received: May 12, 2010
Results First Received: November 12, 2013
Last Updated: March 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Clovis Oncology, Inc.:
cancer
metastatic
pancreatic
pancreas
adenocarcinoma
gemcitabine
human equilibrative nucleoside transporter-1 (hENT1)
CO-1.01
CO-101
CO101
Stage 4
Stage IV

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 30, 2014