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

A Phase II Randomized, Open-Label, Multicenter Study Comparing CO-1.01 With Gemcitabine as First-Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: CO-1.01; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 367
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5004FHP
    • Clinica Universitaria Reina Fabiola
  • Santa Fe, Argentina, S3000FFU
    • ISIS Centro especializado
  • Bahia Blanca
    • Buenos Aires, Bahia Blanca, Argentina, B8000FJI
      • Policlínica Privada Instituto de Medicina Nuclear
  • Buenos Aires
    • Cuidad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
      • Instituto Especializado Alexander Fleming
    • Loma Hermosa, Buenos Aires, Argentina, B1657BHD
      • Hospital de Gastroenterología
• Australia
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • Newcastle Private Hospital
    • Port Macquarie, New South Wales, Australia, 2444
      • Port Macquarie Base Hospital
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Oncology Care Centre
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Saint Vincent's Hospital
    • Wodonga, Victoria, Australia, 3690
      • Border Medical Oncology, Murray Valley Private Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint Luc
  • Haine-Saint-Paul, Belgium, 7100
    • Centre Hospitalier de Jolimont-Lobbes
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen
• Brazil
  • Rio de Janeiro, Brazil, 20231
    • Instituto Nacional do Câncer
  • Distrito Federal
    • Brasilia, Distrito Federal, Brazil, 70840
      • Hospital Universitario
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 60430-230
      • Santa Casa de Misericordia de Belo Horizonte
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90020
      • Irmandade da Santa
  • Santa Catarina
    • Florianópolis, Santa Catarina, Brazil, 88034-000
      • CEPON-Centro de Pesquisas Oncológicas
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Hospital do Cancer de Barretos
    • Jau, Sao Paulo, Brazil, 17210
      • Fundacao Hospital
    • Santo Andre, Sao Paulo, Brazil, 09060-650
      • Faculdade de Medicina do ABC
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
• France
  • Bayonne Cedex, France, 64109
    • Centre Hospitalier de la Cote Basque
  • Bordeaux, France, 33000
    • Hôpital Saint André, Service d'Oncologie Médicale
  • Limoges Cedex, France, 87039
    • Clinique Francois Chenieux
  • Montpellier, France, 34298
    • Centre Regional de Lutte contre le Cancer Val d'Aurelle
  • Montpellier Cedex 5, France, 34295
    • Centre Hospitalier Régional Universitaire Hôpital Saint Eloi
  • Saint Herblain cedex, France, 44805
    • Centre René Gauducheau
  • Villejuif Cedex, France, 94805
    • Institut Gustave-Roussy - Centre de Lutte Contre le Cancer
• Germany
  • Berlin, Germany, 13353
    • Charité Universitätsmedizin Berlin
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus
  • Magdeburg, Germany, 39120
    • Klinik der Otto-Von-Guericke-Universität Magdeburg
  • Ulm, Germany, 89081
    • Medizinische Universitätsklinik Ulm, Abt. Innere Medizin I
  • Bayern
    • München, Bayern, Germany, 81377
      • Ludwig-Maximilians-Universität, Medizinische Klinik und Poliklinikversität München
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
      • Klinikum der Ernst-Moritz-Arndt-Universität
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44892
      • Knappschaftskrankenhaus Bochum-Langendreer
  • Thueringen
    • Jena, Thueringen, Germany, 07740
      • Universitatsklinikum Jena
• Italy
  • Milano, Italy, 20132
    • Fondazione San Raffaele del Monte Tabor
  • Padova, Italy, 35128
    • Instituto Oncologico Veneto, Oncologia Medica 1
  • Torrette di Ancona, Italy, 60020
    • Ospedali Riuniti Di Ancona
  • Verona, Italy, 37134
    • Centro Ricerche Cliniche di Verona
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • Vrije Universiteit Medisch Centrum
• Norway
  • Kristiansand, Norway, 4604
    • Sørlandet Sykehus HF
  • Oslo, Norway, 0407
    • Oslo universitetssykehus, Ullevål
• Russian Federation
  • Ekaterinburg, Russian Federation, 620036
    • Sverdlovsk Regional Oncology Center
  • Irkutsk, Russian Federation, 664035
    • Regional Oncology Center
  • Krasnodar, Russian Federation, 350040
    • Clinical Oncology Center #1
  • Kursk, Russian Federation, 305035
    • Kursk Regional Oncology Center
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center
  • Novosibirsk, Russian Federation, 630047
    • Novosibirsk, City Clinical Hospital #1
  • St. Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinical Hospital
  • St. Petersburg, Russian Federation, 195067
    • Mechnikov St. Petersburg State Medical Academy
  • St. Petersburg, Russian Federation, 197785
    • St. Petersburg City Oncology Center
  • Tambov, Russian Federation, 392013
    • Tambov Regional Oncology Center
  • Tula, Russian Federation, 300053
    • Tula Regional Oncology Center
  • Yaroslavl, Russian Federation, 150040
    • Regional Clinical Oncology Hospital
  • Republic of Udmurtia
    • Izhevsk, Republic of Udmurtia, Russian Federation, 426067
      • Republic Clinical Oncology Center
• Sweden
  • Jonkoping, Sweden, 551 85
    • Länssjukhuset Ryhov
  • Linköping, Sweden, 581 85
    • Linkoping University Hospital
  • Växjö, Sweden, 351 85
    • Växjö Centrallasarettet
• Ukraine
  • Dnipropetrovsk, Ukraine, 49102
    • Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy, Dnipropetrovsk State Medical Academy, Department of Oncology and Medical Radiology
  • Donetsk, Ukraine, 83092
    • Public Clinical Treatment and Prophylaxis Institution "Donetsk Regional Antitumor Center", Oncosurgery Department #6
  • Kharkiv, Ukraine, 61070
    • "Public Healthcare Institution ""Kharkiv Regional Clinical Oncology Center"", Abdominal Department
  • Kiev, Ukraine, 03022
    • National Cancer Institute, Department of Tumors of Abdominal Cavity and Retroperitoneum
  • Lviv, Ukraine, 79031
    • State Regional Diagnostics and Treatment Oncology Center, Chemotherapy Department
  • Mykolayiv, Ukraine, 54044
    • Mykolayiv Regional Oncology Center, Surgery Department #1
  • Uzhorod, Ukraine, 88014
    • Zakarpatya Regional Clinical Oncology Center, Chemotherapy Department
  • Zaporizhya, Ukraine, 69032
    • Clinical Facility: Public Institution "Zaporizhya City Clinical Hospital #3", Regional Center of Hepatic, Biliary Tract and Pancreatic Surgery, Surgery Department #1
• United Kingdom
  • England
    • London, England, United Kingdom, W12 0HS
      • Hammersmith Hospital
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Beatson West of Scotland Cancer Centre, Cancer Research UK Clinical Trials Unit (CTU)
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Center for Hematology Oncology
  • California
    • Corona, California, United States, 92879
      • Wilshire Oncology Medical Group, Inc.
    • Los Angeles, California, United States, 90033
      • White Memorial Medical Center
    • Los Angeles, California, United States, 90036
      • Cancer Care Institute
    • Newport Beach, California, United States, 92660
      • Newport Cancer Care Medical
    • Oakland, California, United States, 94609
      • Hematology Oncology Associates
    • San Diego, California, United States, 92123
      • Sharp Clinical Oncology Research
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital Clinical Research
    • Trumbull, Connecticut, United States, 06611
      • Oncology Associates of Bridgeport
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Annapolis Oncology Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • The Cancer Institute of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Cancer Care Alliance
  • New York
    • Lake Success, New York, United States, 11042
      • Arena Oncology Associates, PC
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Cancer Center Of The Carolinas
  • Texas
    • Corpus Christi, Texas, United States, 78412
      • Cancer Specialists of South Texas, P.A.
    • Harlingen, Texas, United States, 78550
      • Valley Cancer Associates
    • San Antonio, Texas, United States, 78229
      • South Texas Oncology and Hematology, PA
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
Experimental: CO-1.01	Drug: CO-1.01; 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Clovis Oncology, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: May 12, 2010
• First Submitted That Met QC Criteria: May 14, 2010
• First Posted (Estimate): May 17, 2010

Study Record Updates

• Last Update Posted (Estimate): April 17, 2014
• Last Update Submitted That Met QC Criteria: March 12, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: cancer; pancreas; metastatic; gemcitabine; adenocarcinoma; pancreatic; Stage IV; Stage 4; human equilibrative nucleoside transporter-1 (hENT1); CO-1.01; CO-101; CO101
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: CO-101-001