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

Metastatic Pancreatic Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01124786
• Other study ID #: CO-101-001
• Status: Completed
• Phase: Phase 2
• First received: May 12, 2010
• Last updated: March 12, 2014
• Start date: May 2010
• Est. completion date: June 2013

Study information

• Verified date: March 2014
• Source: Clovis Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 367
• Est. completion date: June 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Adenocarcinoma

Intervention

Drug:
• CO-1.01
1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks
• Gemcitabine
1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Clovis Oncology, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  France,  Germany,  Italy,  Netherlands,  Norway,  Russian Federation,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	Overall Survival in All Patients and Patients With hENT1 Expression		Monthly follow up after treatment discontinuation until death, up to 1.5 years	No
Secondary	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	No
Secondary	Cancer Antigen (CA)19-9 Response Rates		Every 4 weeks, up to 1.5 years	No
Secondary	Drug Tolerability and Toxicity		Every week, up to 1.5 years	Yes
Secondary	Change From Baseline in Pain Severity		Every 4 weeks, up to 1.5 years	No
Secondary	Change From Baseline in Health Status		Every 4 weeks, up to 1.5 years	No
Secondary	Pharmacokinetic (PK) Profile of CO-1.01 Based on Sparse Sampling		30 days after first dose	No