Clinical trial NCT01124786: A Study Comparing CO-1.01 With Gemcitabine as First Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma (LEAP)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Pancreatic Adenocarcinoma
Keywords: cancer
metastatic
pancreatic
pancreas
adenocarcinoma
gemcitabine
human equilibrative nucleoside transporter-1 (hENT1)
CO-1.01
CO-101
CO101
Stage 4
Stage IV
Lead sponsor: Clovis Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2010-05-17
Enrollment: 367
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Survival in Patients With Low High Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression
timeFrame: Monthly follow up after treatment discontinuation until death, up to 1.5 years.
Secondary outcomes:
measure: Overall Survival in All Patients and Patients With hENT1 Expression
timeFrame: Monthly follow up after treatment discontinuation until death, up to 1.5 years
measure: ORR, Duration of Response, and Progression Free Survival (PFS) in Patients With Measurable/Evaluable Disease, Using RECIST 1.1, up to 1.5 Years
timeFrame: Every 8 weeks
measure: Cancer Antigen (CA)19-9 Response Rates
timeFrame: Every 4 weeks, up to 1.5 years
measure: Drug Tolerability and Toxicity
timeFrame: Every week, up to 1.5 years
measure: Change From Baseline in Pain Severity
timeFrame: Every 4 weeks, up to 1.5 years
measure: Change From Baseline in Health Status
timeFrame: Every 4 weeks, up to 1.5 years
measure: Pharmacokinetic (PK) Profile of CO-1.01 Based on Sparse Sampling
timeFrame: 30 days after first dose
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Center for Hematology Oncology
state: Arizona
city: Corona
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Los Angeles
country: United States
facility: White Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Cancer Care Institute
state: California
city: Newport Beach
country: United States
facility: Newport Cancer Care Medical
state: California
city: Oakland
country: United States
facility: Hematology Oncology Associates
state: California
city: San Diego
country: United States
facility: Sharp Clinical Oncology Research
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital Clinical Research
state: Connecticut
city: Trumbull
country: United States
facility: Oncology Associates of Bridgeport
state: Connecticut
city: Annapolis
country: United States
facility: Annapolis Oncology Center
state: Maryland
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: New Brunswick
country: United States
facility: The Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Lake Success
country: United States
facility: Arena Oncology Associates, PC
state: New York
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Greenville
country: United States
facility: Cancer Center of the Carolinas
state: South Carolina
city: Corpus Christi
country: United States
facility: Cancer Specialists of South Texas, P.A.
state: Texas
city: Harlingen
country: United States
facility: Valley Cancer Associates
state: Texas
city: San Antonio
country: United States
facility: South Texas Oncology and Hematology, PA
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Policlínica Privada Instituto de Medicina Nuclear
state: Bahia Blanca
city: Cuidad Autónoma de Buenos Aires
country: Argentina
facility: Instituto Especializado Alexander Fleming
state: Buenos Aires
city: Loma Hermosa
country: Argentina
facility: Hospital de Gastroenterología
state: Buenos Aires
city: Córdoba
country: Argentina
facility: Clínica Universitaria Reina Fabiola
city: Santa Fe
country: Argentina
facility: ISIS Centro Especializado
city: New Lambton Heights
country: Australia
facility: Newcastle Private Hospital
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Oncology Care Centre
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Fitzroy
country: Australia
facility: Saint Vincent's Hospital
state: Victoria
city: Wodonga
country: Australia
facility: Border Medical Oncology, Murray Valley Private Hospital
state: Victoria
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Antwerpen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Haine-Saint-Paul
country: Belgium
facility: Centre Hospitalier de Jolimont-Lobbes
city: Brasilia
country: Brazil
facility: Hospital Universitario
state: Distrito Federal
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas - PUCRS
state: Rio Grande Do Sul
city: Florianópolis
country: Brazil
facility: CEPON-Centro de pesquisas Oncologicas
state: Santa Catarina
city: Barretos
country: Brazil
facility: Hospital do Cancer de Barretos
state: Sao Paulo
city: Jau
country: Brazil
facility: Fundacao Hospital
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional do Cancer
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Bayonne Cedex
country: France
facility: Centre Hospitalier de la Cote Basque
city: Bordeaux
country: France
facility: Hôpital Saint André, Service d'Oncologie Médicale
city: Limoges Cedex
country: France
facility: Clinique François Chénieux
city: Montpellier Cedex 5
country: France
facility: Centre Hospitalier Régional Universitaire Hôpital Saint Eloi
city: Montpellier
country: France
facility: Centre Regional de Lutte contre le Cancer Val d'Aurelle
city: Saint Herblain cedex
country: France
facility: Centre René Gauducheau
city: Villejuif Cedex
country: France
facility: Institut Gustave-Roussy - Centre de Lutte Contre le Cancer
city: München
country: Germany
facility: Ludwig-Maximilians-Universität, Medizinische Klinik und Poliklinikversität München
state: Bayern
city: Greifswald
country: Germany
facility: Klinikum der Ernst-Moritz-Arndt-Universität
state: Mecklenburg-Vorpommern
city: Bochum
country: Germany
facility: Knappschaftskrankenhaus Bochum-Langendreer
state: Nordrhein-Westfalen
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thueringen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Magdeburg
country: Germany
facility: Klinik der Otto-Von-Guericke-Universität Magdeburg
city: Ulm
country: Germany
facility: Medizinische Universitätsklinik Ulm, Abt. Innere Medizin I
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
state: Emilia-Romagna
city: Milano
country: Italy
facility: Fondazione San Raffaele del Monte Tabor
city: Padova
country: Italy
facility: Instituto Oncologico Veneto, Oncologia Medica 1
city: Torrette di Ancona
country: Italy
facility: Ospedali Riuniti di Ancona
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
state: Noord-Holland
city: Kristiansand
country: Norway
facility: Sørlandet sykehus HF
city: Oslo
country: Norway
facility: Oslo Universitetssykehus, Ullevål
city: Izhevsk
country: Russian Federation
facility: Republic Clinical Oncology Center
state: Republic of Udmurtia
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Oncology Center
city: Irkutsk
country: Russian Federation
facility: Regional Oncology Center
city: Krasnodar
country: Russian Federation
facility: Clinical Oncology Center #1
city: Kursk
country: Russian Federation
facility: Kursk Regional Oncology Center
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk, City Clinical Hospital #1
city: St. Petersburg
country: Russian Federation
facility: Leningrad Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Mechnikov St. Petersburg State Medical Academy
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg City Oncology Center
city: Tambov
country: Russian Federation
facility: Tambov Regional Oncology Center
city: Tula
country: Russian Federation
facility: Tula Regional Oncology Center
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
city: Jonkoping
country: Sweden
facility: Lanssjukhuset Ryhov
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Växjö
country: Sweden
facility: Växjö Centrallasarettet
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy, Dnipropetrovsk State Medical Academy, Department of Oncology and Medical Radiology
city: Donetsk
country: Ukraine
facility: Public Clinical Treatment and Prophylaxis Institution "Donetsk Regional Antitumor Center", Oncosurgery Department #6
city: Kharkiv
country: Ukraine
facility: "Public Healthcare Institution ""Kharkiv Regional Clinical Oncology Center"", Abdominal Department
city: Kiev
country: Ukraine
facility: National Cancer Institute, Department of Tumors of Abdominal Cavity and Retroperitoneum
city: Lviv
country: Ukraine
facility: State Regional Diagnostics and Treatment Oncology Center, Chemotherapy Department
city: Mykolayiv
country: Ukraine
facility: Mykolayiv Regional Oncology Center, Surgery Department #1
city: Uzhorod
country: Ukraine
facility: Zakarpatya Regional Clinical Oncology Center, Chemotherapy Department
city: Zaporizhya
country: Ukraine
facility: Clinical Facility: Public Institution "Zaporizhya City Clinical Hospital #3", Regional Center of Hepatic, Biliary Tract and Pancreatic Surgery, Surgery Department #1
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre, Cancer Research UK Clinical Trials Unit (CTU)
state: Scotland
Study officials:
References: