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

NCT ID: NCT01124786

Last Updated: 2014-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 367 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2013-06-30

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.

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.

Conditions

Metastatic Pancreatic Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CO-1.01

Group Type: EXPERIMENTAL

CO-1.01

Intervention Type: DRUG

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

gemcitabine

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

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

Interventions

CO-1.01

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

Intervention Type: DRUG

Gemcitabine

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

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clovis Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arizona Center for Hematology Oncology

Glendale, Arizona, United States

Wilshire Oncology Medical Group, Inc.

Corona, California, United States

White Memorial Medical Center

Los Angeles, California, United States

Cancer Care Institute

Los Angeles, California, United States

Newport Cancer Care Medical

Newport Beach, California, United States

Hematology Oncology Associates

Oakland, California, United States

Sharp Clinical Oncology Research

San Diego, California, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Hartford Hospital Clinical Research

Hartford, Connecticut, United States

Oncology Associates of Bridgeport

Trumbull, Connecticut, United States

Annapolis Oncology Center

Annapolis, Maryland, United States

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

The Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Arena Oncology Associates, PC

Lake Success, New York, United States

Bend Memorial Clinic

Bend, Oregon, United States

Cancer Center of the Carolinas

Greenville, South Carolina, United States

Cancer Specialists of South Texas, P.A.

Corpus Christi, Texas, United States

Valley Cancer Associates

Harlingen, Texas, United States

South Texas Oncology and Hematology, PA

San Antonio, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Policlínica Privada Instituto de Medicina Nuclear

Buenos Aires, Bahia Blanca, Argentina

Instituto Especializado Alexander Fleming

Cuidad Autónoma de Buenos Aires, Buenos Aires, Argentina

Hospital de Gastroenterología

Loma Hermosa, Buenos Aires, Argentina

Clínica Universitaria Reina Fabiola

Córdoba, Córdoba Province, Argentina

ISIS Centro Especializado

Santa Fe, Santa Fe Province, Argentina

Newcastle Private Hospital

New Lambton Heights, New South Wales, Australia

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia

Southern Medical Day Oncology Care Centre

Wollongong, New South Wales, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Saint Vincent's Hospital

Fitzroy, Victoria, Australia

Border Medical Oncology, Murray Valley Private Hospital

Wodonga, Victoria, Australia

Universitair Ziekenhuis Antwerpen

Edegem, Antwerpen, Belgium

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Centre Hospitalier de Jolimont-Lobbes

Haine-Saint-Paul, , Belgium

Hospital Universitario

Brasília, Federal District, Brazil

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Instituto Nacional do Cancer

Rio de Janeiro, Rio de Janeiro, Brazil

Irmandade da Santa

Porto Alegre, Rio Grande do Sul, Brazil

Hospital São Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

CEPON-Centro de pesquisas Oncologicas

Florianópolis, Santa Catarina, Brazil

Hospital do Cancer de Barretos

Barretos, São Paulo, Brazil

Fundacao Hospital

Jaú, São Paulo, Brazil

Faculdade de Medicina do ABC

Santo André, São Paulo, Brazil

Cross Cancer Institute

Edmonton, Alberta, Canada

Centre Hospitalier de la Cote Basque

Bayonne, , France

Hôpital Saint André, Service d'Oncologie Médicale

Bordeaux, , France

Clinique François Chénieux

Limoges, , France

Centre Hospitalier Régional Universitaire Hôpital Saint Eloi

Montpellier, , France

Centre Regional de Lutte contre le Cancer Val d'Aurelle

Montpellier, , France

Centre René Gauducheau

Saint-Herblain, , France

Institut Gustave-Roussy - Centre de Lutte Contre le Cancer

Villejuif, , France

Ludwig-Maximilians-Universität, Medizinische Klinik und Poliklinikversität München

München, Bavaria, Germany

Klinikum der Ernst-Moritz-Arndt-Universität

Greifswald, Mecklenburg-Vorpommern, Germany

Knappschaftskrankenhaus Bochum-Langendreer

Bochum, North Rhine-Westphalia, Germany

Universitätsklinikum Jena

Jena, Thuringia, Germany

Charité Universitätsmedizin Berlin

Berlin, , Germany

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Klinik der Otto-Von-Guericke-Universität Magdeburg

Magdeburg, , Germany

Medizinische Universitätsklinik Ulm, Abt. Innere Medizin I

Ulm, , Germany

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

Bologna, Emilia-Romagna, Italy

Instituto Oncologico Veneto, Oncologia Medica 1

Padua, Padova, Italy

Fondazione San Raffaele del Monte Tabor

Milan, , Italy

Ospedali Riuniti di Ancona

Torrette Di Ancona, , Italy

Centro Ricerche Cliniche di Verona

Verona, , Italy

Vrije Universiteit Medisch Centrum

Amsterdam, North Holland, Netherlands

Sørlandet sykehus HF

Kristiansand, , Norway

Oslo Universitetssykehus, Ullevål

Oslo, , Norway

Republic Clinical Oncology Center

Izhevsk, Udmurtiya Republic, Russia

Regional Oncology Center

Irkutsk, , Russia

Clinical Oncology Center #1

Krasnodar, , Russia

Kursk Regional Oncology Center

Kursk, , Russia

Blokhin Cancer Research Center

Moscow, , Russia

Novosibirsk, City Clinical Hospital #1

Novosibirsk, , Russia

Leningrad Regional Clinical Hospital

Saint Petersburg, , Russia

Mechnikov St. Petersburg State Medical Academy

Saint Petersburg, , Russia

St. Petersburg City Oncology Center

Saint Petersburg, , Russia

Tambov Regional Oncology Center

Tambov, , Russia

Tula Regional Oncology Center

Tula, , Russia

Regional Clinical Oncology Hospital

Yaroslavl, , Russia

Sverdlovsk Regional Oncology Center

Yekaterinburg, , Russia

Lanssjukhuset Ryhov

Jönköping, , Sweden

Linköping University Hospital

Linköping, , Sweden

Växjö Centrallasarettet

Vaxjo, , Sweden

Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy, Dnipropetrovsk State Medical Academy, Department of Oncology and Medical Radiology

Dnipropetrovsk, , Ukraine

Public Clinical Treatment and Prophylaxis Institution "Donetsk Regional Antitumor Center", Oncosurgery Department #6

Donetsk, , Ukraine

"Public Healthcare Institution ""Kharkiv Regional Clinical Oncology Center"", Abdominal Department

Kharkiv, , Ukraine

National Cancer Institute, Department of Tumors of Abdominal Cavity and Retroperitoneum

Kiev, , Ukraine

State Regional Diagnostics and Treatment Oncology Center, Chemotherapy Department

Lviv, , Ukraine

Mykolayiv Regional Oncology Center, Surgery Department #1

Mykolayiv, , Ukraine

Zakarpatya Regional Clinical Oncology Center, Chemotherapy Department

Uzhhorod, , Ukraine

Clinical Facility: Public Institution "Zaporizhya City Clinical Hospital #3", Regional Center of Hepatic, Biliary Tract and Pancreatic Surgery, Surgery Department #1

Zaporizhya, , Ukraine

Hammersmith Hospital

London, England, United Kingdom

Christie Hospital

Manchester, England, United Kingdom

Beatson West of Scotland Cancer Centre, Cancer Research UK Clinical Trials Unit (CTU)

Glasgow, Scotland, United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; France; Germany; Italy; Netherlands; Norway; Russia; Sweden; Ukraine; United Kingdom

Other Identifiers

CO-101-001

Identifier Type: -

Identifier Source: org_study_id