A Study Comparing CO-1.01 With Gemcitabine as First Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma (LEAP)
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Interventions
- Registration Number
- NCT01124786
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 367
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CO-1.01 CO-1.01 - gemcitabine Gemcitabine -
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Trial Locations
- Locations (95)
Newport Cancer Care Medical
🇺🇸Newport Beach, California, United States
White Memorial Medical Center
🇺🇸Los Angeles, California, United States
Saint Vincent's Hospital
🇦🇺Fitzroy, Victoria, Australia
Centre Hospitalier de Jolimont-Lobbes
🇧🇪Haine-Saint-Paul, Belgium
"Public Healthcare Institution ""Kharkiv Regional Clinical Oncology Center"", Abdominal Department
🇺🇦Kharkiv, Ukraine
Zakarpatya Regional Clinical Oncology Center, Chemotherapy Department
🇺🇦Uzhorod, Ukraine
Christie Hospital
🇬🇧Manchester, England, United Kingdom
Hospital Universitario
🇧🇷Brasilia, Distrito Federal, Brazil
Hospital São Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Bend Memorial Clinic
🇺🇸Bend, Oregon, United States
Fondazione San Raffaele del Monte Tabor
🇮🇹Milano, Italy
Annapolis Oncology Center
🇺🇸Annapolis, Maryland, United States
Southern Medical Day Oncology Care Centre
🇦🇺Wollongong, New South Wales, Australia
Centre Hospitalier de la Cote Basque
🇫🇷Bayonne Cedex, France
Knappschaftskrankenhaus Bochum-Langendreer
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Policlínica Privada Instituto de Medicina Nuclear
🇦🇷Buenos Aires, Bahia Blanca, Argentina
Clínica Universitaria Reina Fabiola
🇦🇷Córdoba, Argentina
Sharp Clinical Oncology Research
🇺🇸San Diego, California, United States
ISIS Centro Especializado
🇦🇷Santa Fe, Argentina
Hospital do Cancer de Barretos
🇧🇷Barretos, Sao Paulo, Brazil
Hospital de Gastroenterología
🇦🇷Loma Hermosa, Buenos Aires, Argentina
Hartford Hospital Clinical Research
🇺🇸Hartford, Connecticut, United States
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
New Mexico Cancer Care Alliance
🇺🇸Albuquerque, New Mexico, United States
Wilshire Oncology Medical Group, Inc.
🇺🇸Corona, California, United States
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Arizona Center for Hematology Oncology
🇺🇸Glendale, Arizona, United States
South Texas Oncology and Hematology, PA
🇺🇸San Antonio, Texas, United States
Vrije Universiteit Medisch Centrum
🇳🇱Amsterdam, Noord-Holland, Netherlands
Regional Oncology Center
🇷🇺Irkutsk, Russian Federation
Oncology Associates of Bridgeport
🇺🇸Trumbull, Connecticut, United States
Valley Cancer Associates
🇺🇸Harlingen, Texas, United States
Public Clinical Treatment and Prophylaxis Institution "Donetsk Regional Antitumor Center", Oncosurgery Department #6
🇺🇦Donetsk, Ukraine
Lanssjukhuset Ryhov
🇸🇪Jonkoping, Sweden
Instituto Oncologico Veneto, Oncologia Medica 1
🇮🇹Padova, Italy
Mechnikov St. Petersburg State Medical Academy
🇷🇺St. Petersburg, Russian Federation
Hôpital Saint André, Service d'Oncologie Médicale
🇫🇷Bordeaux, France
Centre Regional de Lutte contre le Cancer Val d'Aurelle
🇫🇷Montpellier, France
Medizinische Universitätsklinik Ulm, Abt. Innere Medizin I
🇩🇪Ulm, Germany
Växjö Centrallasarettet
🇸🇪Växjö, Sweden
Centro Ricerche Cliniche di Verona
🇮🇹Verona, Italy
Regional Clinical Oncology Hospital
🇷🇺Yaroslavl, Russian Federation
Clinical Oncology Center #1
🇷🇺Krasnodar, Russian Federation
Novosibirsk, City Clinical Hospital #1
🇷🇺Novosibirsk, Russian Federation
Sverdlovsk Regional Oncology Center
🇷🇺Ekaterinburg, Russian Federation
Linköping University Hospital
🇸🇪Linköping, Sweden
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Clinique François Chénieux
🇫🇷Limoges Cedex, France
Centre René Gauducheau
🇫🇷Saint Herblain cedex, France
Kursk Regional Oncology Center
🇷🇺Kursk, Russian Federation
Tambov Regional Oncology Center
🇷🇺Tambov, Russian Federation
Tula Regional Oncology Center
🇷🇺Tula, Russian Federation
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Hematology Oncology Associates
🇺🇸Oakland, California, United States
Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Arena Oncology Associates, PC
🇺🇸Lake Success, New York, United States
The Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Cancer Specialists of South Texas, P.A.
🇺🇸Corpus Christi, Texas, United States
Cancer Center of the Carolinas
🇺🇸Greenville, South Carolina, United States
Port Macquarie Base Hospital
🇦🇺Port Macquarie, New South Wales, Australia
Fundacao Hospital
🇧🇷Jau, Sao Paulo, Brazil
Instituto Nacional do Cancer
🇧🇷Rio de Janeiro, Brazil
Institut Gustave-Roussy - Centre de Lutte Contre le Cancer
🇫🇷Villejuif Cedex, France
Ludwig-Maximilians-Universität, Medizinische Klinik und Poliklinikversität München
🇩🇪München, Bayern, Germany
Ospedali Riuniti di Ancona
🇮🇹Torrette di Ancona, Italy
St. Petersburg City Oncology Center
🇷🇺St. Petersburg, Russian Federation
Blokhin Cancer Research Center
🇷🇺Moscow, Russian Federation
Leningrad Regional Clinical Hospital
🇷🇺St. Petersburg, Russian Federation
Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy, Dnipropetrovsk State Medical Academy, Department of Oncology and Medical Radiology
🇺🇦Dnipropetrovsk, Ukraine
National Cancer Institute, Department of Tumors of Abdominal Cavity and Retroperitoneum
🇺🇦Kiev, Ukraine
Newcastle Private Hospital
🇦🇺New Lambton Heights, New South Wales, Australia
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Cancer Care Institute
🇺🇸Los Angeles, California, United States
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Faculdade de Medicina do ABC
🇧🇷Santo Andre, Sao Paulo, Brazil
Centre Hospitalier Régional Universitaire Hôpital Saint Eloi
🇫🇷Montpellier Cedex 5, France
Universitätsklinikum Jena
🇩🇪Jena, Thueringen, Germany
Klinik der Otto-Von-Guericke-Universität Magdeburg
🇩🇪Magdeburg, Germany
Republic Clinical Oncology Center
🇷🇺Izhevsk, Republic of Udmurtia, Russian Federation
Instituto Especializado Alexander Fleming
🇦🇷Cuidad Autónoma de Buenos Aires, Buenos Aires, Argentina
Mykolayiv Regional Oncology Center, Surgery Department #1
🇺🇦Mykolayiv, Ukraine
Clinical Facility: Public Institution "Zaporizhya City Clinical Hospital #3", Regional Center of Hepatic, Biliary Tract and Pancreatic Surgery, Surgery Department #1
🇺🇦Zaporizhya, Ukraine
CEPON-Centro de pesquisas Oncologicas
🇧🇷Florianópolis, Santa Catarina, Brazil
Border Medical Oncology, Murray Valley Private Hospital
🇦🇺Wodonga, Victoria, Australia
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Antwerpen, Belgium
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Sørlandet sykehus HF
🇳🇴Kristiansand, Norway
Oslo Universitetssykehus, Ullevål
🇳🇴Oslo, Norway
State Regional Diagnostics and Treatment Oncology Center, Chemotherapy Department
🇺🇦Lviv, Ukraine
Klinikum der Ernst-Moritz-Arndt-Universität
🇩🇪Greifswald, Mecklenburg-Vorpommern, Germany
Hammersmith Hospital
🇬🇧London, England, United Kingdom
Irmandade da Santa
🇧🇷Porto Alegre, Rio Grande do Sul, Brazil
Beatson West of Scotland Cancer Centre, Cancer Research UK Clinical Trials Unit (CTU)
🇬🇧Glasgow, Scotland, United Kingdom