Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine For Advanced Pancreatic Cancer.

Carcinoma, Pancreatic Ductal Clinical Trial

Official title:

A Randomized, Double-Blind Phase 3 Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine Plus Placebo For The First-Line Treatment Of Patients With Locally Advanced, Unresectable Or Metastatic Pancreatic Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00471146
• Other study ID #: A4061028
• Status: Completed
• Phase: Phase 3
• First received: May 7, 2007
• Last updated: June 14, 2012
• Start date: July 2007
• Est. completion date: November 2010

Study information

• Verified date: June 2012
• Source: Pfizer
• 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 investigational study drug, AG-013736, and gemcitabine are effective in the first-line treatment of advanced pancreatic cancer.

Description:

This study was prematurely discontinued for futility on 23 January 2009, based on a planned interim analysis by an independent Data Safety Monitoring Board (DSMB) that found no evidence of improvement in the primary endpoint (survival) in patients treated with axitinib and gemcitabine compared to gemcitabine alone. Enrollment on this study has been discontinued.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 630
• Est. completion date: November 2010
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed, metastatic or locally-, advanced pancreatic adenocarcinoma not amenable to curative resection.

• Adequate renal, hepatic and bone marrow function.

• Performance status 0 or 1.

Exclusion Criteria:

• Prior treatment with any systemic chemotherapy for metastatic disease.

• Prior treatment with gemcitabine, AG-013736, or other vascular endothelial growth factor inhibitors.

• Current or recent bleeding, thromboembolic event and or use of a thrombolytic agent.

• Inability to take oral medication.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Pancreatic Ductal
• Pancreatic Neoplasms

Intervention

Drug:
• AG-013736
oral administration, starting dose 5 mg twice daily [BID] every day until unacceptable toxicity or tumor progression.
• Gemcitabine
intravenous administration at 1,000 mg/m^2 day 1, day 8 and day 15 every 4 weeks (conventional dose) until unacceptable toxicity or tumor progression.
• Gemcitabine
intravenous administration at 1,000 mg/m^2 day 1, day 8 and day 15 every 4 weeks (conventional dose) until unacceptable toxicity or tumor progression.
• placebo
placebo

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Bahia Blanca	Buenos Aires
Argentina	Pfizer Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	Pfizer Investigational Site	La Plata	Buenos Aires
Argentina	Pfizer Investigational Site	Santa Fe
Australia	Pfizer Investigational Site	Clayton	Victoria
Australia	Pfizer Investigational Site	East Bentleigh	Victoria
Australia	Pfizer Investigational Site	St. Leonards	New South Wales
Australia	Pfizer Investigational Site	Wollongong	New South Wales
Austria	Pfizer Investigational Site	Salzburg
Austria	Pfizer Investigational Site	Wels
Austria	Pfizer Investigational Site	Wien
Austria	Pfizer Investigational Site	Wien
Austria	Pfizer Investigational Site	Wien
Belgium	Pfizer Investigational Site	Brussel
Belgium	Pfizer Investigational Site	Bruxelles
Belgium	Pfizer Investigational Site	Bruxelles
Belgium	Pfizer Investigational Site	Gent
Belgium	Pfizer Investigational Site	Leuven
Belgium	Pfizer Investigational Site	Wilrijk
Canada	Pfizer Investigational Site	Edmonton	Alberta
Canada	Pfizer Investigational Site	Kelowna	British Columbia
Canada	Pfizer Investigational Site	Kingston	Ontario
Canada	Pfizer Investigational Site	Kingston	Ontario
Canada	Pfizer Investigational Site	Moncton	New Brunswick
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Oshawa	Ontario
Canada	Pfizer Investigational Site	Toronto	Ontario
Canada	Pfizer Investigational Site	Victoria	British Columbia
Canada	Pfizer Investigational Site	Winnipeg	Manitoba
Canada	Pfizer Investigational Site	Winnipeg	Manitoba
France	Pfizer Investigational Site	Clichy cedex
France	Pfizer Investigational Site	La Chaussee Saint Victor
France	Pfizer Investigational Site	Marseille
France	Pfizer Investigational Site	Montpellier Cedex 02
France	Pfizer Investigational Site	Paris
France	Pfizer Investigational Site	PARIS Cedex 13
France	Pfizer Investigational Site	Pessac Cedex
France	Pfizer Investigational Site	Rouen
France	Pfizer Investigational Site	St Herblain Cedex
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Dresden
Germany	Pfizer Investigational Site	Essen
Germany	Pfizer Investigational Site	Greifswald
Germany	Pfizer Investigational Site	Magdeburg
Germany	Pfizer Investigational Site	Mannheim
Germany	Pfizer Investigational Site	Muenchen
Germany	Pfizer Investigational Site	Oldenburg
Germany	Pfizer Investigational Site	Ulm
Hong Kong	Pfizer Investigational Site	Shatin	NT
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Kaposvar
Hungary	Pfizer Investigational Site	Szentes
Hungary	Pfizer Investigational Site	Zalaegerszeg
India	Pfizer Investigational Site	Ahmedabad	Gujarat
India	Pfizer Investigational Site	Andhra	Pradesh
India	Pfizer Investigational Site	Bangalore	Karnataka
India	Pfizer Investigational Site	Chennai	Tamil Nadu
India	Pfizer Investigational Site	Cochin	Kerala
Ireland	Pfizer Investigational Site	Dublin
Ireland	Pfizer Investigational Site	Dublin 24
Italy	Pfizer Investigational Site	Bologna
Italy	Pfizer Investigational Site	Catania
Italy	Pfizer Investigational Site	Milano
Italy	Pfizer Investigational Site	Milano
Italy	Pfizer Investigational Site	Padova
Italy	Pfizer Investigational Site	Verona
Japan	Pfizer Investigational Site	Chiba city	Chiba
Japan	Pfizer Investigational Site	Chiba-shi	Chiba-ken
Japan	Pfizer Investigational Site	Chuo-ku	Tokyo
Japan	Pfizer Investigational Site	Fukuoka-shi	Fukuoka-ken
Japan	Pfizer Investigational Site	Kashiwa-shi	Chiba
Japan	Pfizer Investigational Site	Nagoya	Aichi
Japan	Pfizer Investigational Site	Osaka-shi	Osaka-fu
Japan	Pfizer Investigational Site	Suntougun	Shizuoka
Japan	Pfizer Investigational Site	Yokohama-shi	Kanagawa
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Netherlands	Pfizer Investigational Site	Amsterdam	Noord Holland
Netherlands	Pfizer Investigational Site	Amsterdam
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Moscow
Russian Federation	Pfizer Investigational Site	Omsk
Russian Federation	Pfizer Investigational Site	Sochi
Russian Federation	Pfizer Investigational Site	St. Petersburg
Russian Federation	Pfizer Investigational Site	St. Petersburg
Singapore	Pfizer Investigational Site	Singapore
Singapore	Pfizer Investigational Site	Singapore
South Africa	Pfizer Investigational Site	Cape Town
South Africa	Pfizer Investigational Site	Observatory
South Africa	Pfizer Investigational Site	Parktown
South Africa	Pfizer Investigational Site	Port Elizabeth
South Africa	Pfizer Investigational Site	Pretoria
South Africa	Pfizer Investigational Site	Sandton
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Las Palmas de Gran Canaria
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Malaga
Spain	Pfizer Investigational Site	Mostoles	Madrid
Spain	Pfizer Investigational Site	Palma de Mallorca	Islas Baleares
Spain	Pfizer Investigational Site	Pamplona	Navarra
Spain	Pfizer Investigational Site	Santa Cruz de Tenerife
Spain	Pfizer Investigational Site	Toledo
Sweden	Pfizer Investigational Site	Lund
Sweden	Pfizer Investigational Site	Uppsala
Switzerland	Pfizer Investigational Site	Winterthur
Taiwan	Pfizer Investigational Site	Kuei-Shan Jsoamg	Taoyuan County
Taiwan	Pfizer Investigational Site	Taichung
Taiwan	Pfizer Investigational Site	Taipei
United Kingdom	Pfizer Investigational Site	Birmingham
United Kingdom	Pfizer Investigational Site	Birmingham
United Kingdom	Pfizer Investigational Site	Edinburgh
United Kingdom	Pfizer Investigational Site	Leicester	Leicestershire
United Kingdom	Pfizer Investigational Site	London
United Kingdom	Pfizer Investigational Site	London
United Kingdom	Pfizer Investigational Site	Maidstone	Kent
United Kingdom	Pfizer Investigational Site	Manchester
United Kingdom	Pfizer Investigational Site	Northwood	Middlesex
United Kingdom	Pfizer Investigational Site	Southhampton
United Kingdom	Pfizer Investigational Site	Whitchurch	Cardiff
United Kingdom	Pfizer Investigational Site	Withington	Manchester
United States	Pfizer Investigational Site	Alton	Illinois
United States	Pfizer Investigational Site	Annapolis	Maryland
United States	Pfizer Investigational Site	Antioch	California
United States	Pfizer Investigational Site	Atlanta	Georgia
United States	Pfizer Investigational Site	Augusta	Georgia
United States	Pfizer Investigational Site	Augusta	Georgia
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Baton Rouge	Louisiana
United States	Pfizer Investigational Site	Baton Rouge	Louisiana
United States	Pfizer Investigational Site	Beech Grove	Indiana
United States	Pfizer Investigational Site	Billings	Montana
United States	Pfizer Investigational Site	Burlington	Massachusetts
United States	Pfizer Investigational Site	Canton	Ohio
United States	Pfizer Investigational Site	Chicago	Illinois
United States	Pfizer Investigational Site	Coeur D'Alene	Idaho
United States	Pfizer Investigational Site	Columbus	Mississippi
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	Corinth	Mississippi
United States	Pfizer Investigational Site	Corona	California
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Everett	Washington
United States	Pfizer Investigational Site	Federal Way	Washington
United States	Pfizer Investigational Site	Glendora	California
United States	Pfizer Investigational Site	Hollywood	Florida
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Jeffersonville	Indiana
United States	Pfizer Investigational Site	Kalamazoo	Michigan
United States	Pfizer Investigational Site	Kennewick	Washington
United States	Pfizer Investigational Site	Knoxville	Tennessee
United States	Pfizer Investigational Site	Knoxville	Tennessee
United States	Pfizer Investigational Site	Knoxville	Tennessee
United States	Pfizer Investigational Site	La Jolla	California
United States	Pfizer Investigational Site	La Jolla	California
United States	Pfizer Investigational Site	Lakewood	Washington
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	LaVerne	California
United States	Pfizer Investigational Site	Lincoln	Nebraska
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Lynchburg	Virginia
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Mineola	New York
United States	Pfizer Investigational Site	Pamona	California
United States	Pfizer Investigational Site	Pasadena	California
United States	Pfizer Investigational Site	Peabody	Massachusetts
United States	Pfizer Investigational Site	Pembroke Pines	Florida
United States	Pfizer Investigational Site	Pleasent Hill	California
United States	Pfizer Investigational Site	Pomona	California
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Puyallup	Washington
United States	Pfizer Investigational Site	Rancho Cucamonga	California
United States	Pfizer Investigational Site	Rancho Mirage	California
United States	Pfizer Investigational Site	Redlands	California
United States	Pfizer Investigational Site	Round Rock	Texas
United States	Pfizer Investigational Site	Salt Lake City	Utah
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Leandro	California
United States	Pfizer Investigational Site	Shelbyville	Kentucky
United States	Pfizer Investigational Site	Southaven	Mississippi
United States	Pfizer Investigational Site	St. Louis	Missouri
United States	Pfizer Investigational Site	Stuart	Florida
United States	Pfizer Investigational Site	Sylvania	Ohio
United States	Pfizer Investigational Site	Syracuse	New York
United States	Pfizer Investigational Site	Tacoma	Washington
United States	Pfizer Investigational Site	Tampa	Florida
United States	Pfizer Investigational Site	Tupelo	Mississippi
United States	Pfizer Investigational Site	West Covina	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Hong Kong,  Hungary,  India,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 7. 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 until death or at least 1 year after the randomization of last participant	No
Secondary	Progression Free Survival (PFS)	Time in weeks from randomization to the first documentation of objective tumor progression or death due to any cause. PFS was calculated as = (first event date minus randomization date plus 1) divided by 7. 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").	Baseline until disease progression or at least 1 year after the randomization of last participant	No
Secondary	Percentage of Participants With Objective 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 response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.	Baseline, every 8 weeks until tumor progression or death	No
Secondary	Duration of Response (DR)	Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. 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) divided by 7.	Baseline until death or at least 1 year after the randomization of last participant	No
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status (GHS), 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.	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal	No
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score	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= greater degree of symptoms or treatment side effects and emotional issues.	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal	No
Secondary	Change From Baseline Brief Pain Inventory-short Form (BPI-sf) Score	BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference.	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal	No
Secondary	Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal	No
Secondary	Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) VAS Score	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.	Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal	No
Secondary	Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736)	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.	Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 23 months	No

External Links

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