AG-013736 In Combination With Gemcitabine Versus Gemcitabine Alone For Patients With Metastatic Pancreatic Cancer

Pancreatic Neoplasms Clinical Trial

Official title:

A RANDOMIZED PHASE 2 STUDY OF THE ANTI-ANGIOGENESIS AGENT AG-013736 IN COMBINATION WITH GEMCITABINE IN PATIENTS WITH CHEMOTHERAPY-NAIVE ADVANCED PANCREATIC CANCER PRECEDED BY A PHASE 1 PORTION

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00219557
• Other study ID #: A4061016
• Secondary ID: 2005-000053-30
• Status: Completed
• Phase: Phase 2
• Start date: July 5, 2005
• Est. completion date: March 14, 2008

Study information

• Verified date: April 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2 study being conducted at multiple centers in the United States, Europe and Canada. Patients having pancreatic cancer that is locally advanced or that has spread to other parts of the body (i.e., metastatic) are eligible to participate. Patients must have not had any prior systemic treatment for advanced disease. The purpose of the study is to test whether the angiogenesis inhibitor Axitinib [AG-013736] in combination with gemcitabine is an effective treatment for advanced pancreatic cancer vs. gemcitabine alone by overall survival.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: March 14, 2008
• Est. primary completion date: March 14, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with advanced (localized but surgically unresectable or metastatic) histologically/cytologically proven epithelial cancer of the exocrine pancreas

• no prior therapy for metastatic disease

Exclusion Criteria:

• patients with locally advanced disease who are candidates for radiation therapy.

• uncontrolled brain metastases (a controlled brain metastasis must be previously treated, asymptomatic, and without growth for 4 months)

Related Conditions & MeSH terms

• Pancreatic Neoplasms

Intervention

Drug:
• Gemcitabine
Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks
• AG-013736
Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 4 weeks.
• Gemcitabine
Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent/Dienst Gastroenterologie	Gent
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CHUM, Hopital Saint-Luc	Montreal	Quebec
Canada	Sault Area Hospital	Sault Ste Marie	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Canada	CancerCare Manitoba	Winnipeg	Manitoba
France	Hopital La Timone	Marseille
France	Hopital de la Pitie Salpetriere	Paris Cedex 13
France	Service Oncologie Medicale	Saint-Herblain	Saint Herblain Cedex
France	Institut Claudius Regaud	Toulouse
Germany	Medizinische Klinik mit Schwerpunkt Haematologie und Onkologie, Charité-Universitaetsmedizin Berlin	Berlin
Italy	Fondazione IRCCS, Istituto Nazionale Tumori, Oncologia Medica B	Milano
Italy	Unita Operativa, Oncologia Medica, Istituto di Medicina Interna e Geriatria	Roma
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital Universitario Vall D´Hebron	Barcelona
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
United Kingdom	Western General Hospitals Nhs Trust	Edinburgh
United Kingdom	Department of Cancer Studies & Molecular Medicine	Leicester	Leicestershire
United Kingdom	Hammersmith Hospital	London
United Kingdom	Cancer Research Uk Clinical Centre	Southampton	Hampshire
United States	East Bay Medical Oncology/Hematology Medical Associates Inc.	Antioch	California
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Maine Center for Cancer Medicine and Blood Disorders	Biddeford	Maine
United States	Maine Center for Cancer Medicine and Blood Disorders	Brunswick	Maine
United States	Bay Area Cancer Research Group	Concord	California
United States	East Bay Medical Oncology/Hematology Medical Associates, Inc.	Concord	California
United States	Southeast Nebraska Cancer Center, Southeast Nebraska Hematology and Oncology Consultants, P.C.	Lincoln	Nebraska
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Jackson Memorial Hospital & Clinics	Miami	Florida
United States	University of Miami Hospital & clinics	Miami	Florida
United States	Arch Medical Services, Inc. d/b/a The Center for Cancer Care and Research	Saint Louis	Missouri
United States	Maine Center for Cancer Medicine and Blood Disorders	Scarborough	Maine
United States	Hematology Oncology, P.C.	Stamford	Connecticut
United States	H Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Arch Medical Services, Inc. d/b/a The Center for Cancer Care and Research	Washington	Missouri
United States	Piedmont Hematology Oncology Associates	Winston-Salem	North Carolina
United States	Piedmont Hematology Oncology Association	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Time in days from randomization to date of death due to any cause. OS was calculated as the death date minus the date of randomization plus 1. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).	Baseline of Phase 2 to death or until at least 1 year after the randomization of the last participant
Secondary	Dose Confirmation of Axitinib (AG-013736) on Basis of Number of Participants With Dose Limiting Toxicity (DLT)	Dose of axitinib (AG-013736) was confirmed if not more than 1 out of 6 participants experienced a DLT during first cycle. DLT included grade (Gr) 4 neutropenia or thrombocytopenia, greater than or equal to (>=) Gr 3 anemia or non hematological toxicities for >= 7 days (except alopecia) or >= Gr 1 hemoptysis or >=2 gram /24 hours proteinuria or inability to resume background chemotherapy or axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.	Phase 1 baseline up to Week 4
Secondary	Dose Confirmation of Gemcitabine on Basis of Number of Participants With Dose Limiting Toxicity (DLT)	Dose of gemcitabine was confirmed if not more than 1 out of 6 participants experienced a DLT during first cycle. DLT included grade (Gr) 4 neutropenia or thrombocytopenia, greater than or equal to (>=) Gr 3 anemia or non hematological toxicities for >= 7 days (except alopecia) or >= Gr 1 hemoptysis or >=2 gram /24 hours proteinuria or inability to resume background chemotherapy or axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.	Phase 1 Baseline up to Week 4
Secondary	Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)		0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hours (hr) post-dose on Day 15 of Phase 1 Cycle 1
Secondary	Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] of Axitinib (AG-013736)	AUC (0-24) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to 24 hours (0-24).	0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib (AG-013736)	Tmax was based on the actual time points when the samples were collected.	0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1
Secondary	Plasma Decay Half-life (t1/2) of Axitinib (AG-013736)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1
Secondary	Maximum Observed Plasma Concentration (Cmax) of Gemcitabine		0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1
Secondary	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of Gemcitabine	AUC (0 - 8) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1
Secondary	Plasma Decay Half-life (t1/2) of Gemcitabine	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1
Secondary	Population Pharmacokinetics of Axitinib (AG-013736) in Phase 2	Data for this outcome measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Phase 2 Day 1 (Pre-dose), Day 29, Day 57 and then every 8 weeks until disease progression or discontinuation from study or up to 80 weeks
Secondary	Percentage of Participants With Overall Response (OR)	Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non-target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum of longest dimensions.	Phase 2 baseline to disease progression or discontinuation from study, assessed every 8 weeks up to 80 weeks
Secondary	Duration of Response (DR)	Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.	Phase 2 baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 80 weeks
Secondary	Progression-free Survival (PFS)	Time in days from randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of randomization plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").	Phase 2 baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 80 weeks
Secondary	One Year Survival Probability	One year survival probability was defined as the probability of survival at one year after the date of randomization based on the Kaplan Meier estimate.	Phase 2 baseline to disease progression or death due to any cause or at least 1 year after the first dose for the last participant
Secondary	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score at Day 1 of Every Cycle and End of Study	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. Change from baseline=Cycle/Day score minus baseline score.	Phase 2 baseline [Day (D)1 of Cycle (C)1], Day 1 of all subsequent cycles up to Cycle 14 and end of study (EoS).
Secondary	Change From Baseline in 26-item Pancreatic Cancer-specific Quality of Life Questionnaire (QLQ-PAN26) Score at Day 1 of Every Cycle and End of Study	QLQ-PAN26 consists of 26 questions (Qs) relating to disease symptoms, treatment (Tx) side effects and emotional issues specific to pancreatic cancer (PC). Questions include on altered bowel habits, pain, dietary changes, disease and Tx-related symptoms and issues related to the emotional and social well-being of participants with PC. All 26 Qs are answered on 4-point Likert scale ranging from '1=not at all' to 4='very much' and subsequently transformed into scales that range from 0-100. Higher scores on functioning scales=better functioning; higher scores on the symptom scales=more symptoms.	Phase 2 baseline [Day (D) 1 of Cycle (C)1], Day 1 of all subsequent cycles up to Cycle 14 and end of study (EoS).

External Links

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