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Gemcitabine With/Out Erlotinib in Unresectable Locally Advanced/Metastatic Pancreatic Cancer

Sponsor
NCIC Clinical Trials Group (Other)
Overall Status
Completed
CT.gov ID
NCT00026338
Collaborator
(none)
569
Enrollment
173
Locations
2
Arms
87.4
Actual Duration (Months)
3.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies such as erlotinib use different ways to stimulate the immune system and stop cancer cells from growing. Combining chemotherapy and biological therapy may kill more tumor cells. It is not yet known if gemcitabine is more effective with or without erlotinib in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of gemcitabine with and without erlotinib in treating patients who have unresectable locally advanced or metastatic pancreatic cancer.

Condition or Disease Intervention/Treatment Phase
  • Drug: erlotinib hydrochloride
  • Drug: gemcitabine hydrochloride
 Phase 3

Detailed Description

OBJECTIVES:

  • Compare the overall survival rate in patients with unresectable locally advanced or metastatic pancreatic cancer treated with gemcitabine with or without erlotinib.

  • Compare the progression-free survival rate in patients treated with these regimens.

  • Compare the quality of life of patients treated with these regimens.

  • Compare the response rate and response duration in patients treated with these regimens.

  • Compare the nature, severity, and frequency of toxic effects of these regimens in these patients.

  • Correlate the expression of tissue epidermal growth factor receptor levels at diagnosis with outcome and response in patients treated with these regimens.

  • Determine the pharmacokinetics of erlotinib in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center, extent of disease (locally advanced vs metastatic), and ECOG performance status (0-1 vs 2). Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 of course 1 only, which lasts 8 weeks, and on days 1, 8, and 15 of all subsequent courses, which last 4 weeks each. Patients also receive 1 of 2 doses of oral erlotinib once daily.

  • Arm II: Patients receive gemcitabine as in arm I and 1 of 2 doses of oral placebo once daily.

Treatment continues in both arms in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, on day 29 of course 1, on day 1 of all subsequent courses, at 4 weeks after study, and then every 12 weeks until disease progression.

Patients are followed at 4 weeks and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 800 patients (400 per treatment arm) will be accrued for this study within 11 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
569 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized Placebo Controlled Study Of OSI-774 (TARCEVA) Plus Gemcitabine In Patients With Locally Advanced, Unresectable Or Metastatic Pancreatic Cancer
Actual Study Start Date :
Oct 29, 2001
Actual Primary Completion Date :
Sep 17, 2004
Actual Study Completion Date :
Feb 10, 2009

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: OSI-774 plus Gemcitabine

Drug: erlotinib hydrochloride
150 mg po daily

Drug: gemcitabine hydrochloride
1000 mg/m2 IV weekly (Cycle 1 -Day 1, 8, 15, 22, 29, 36, 43 of an 8 week cycle, Cycle 2 and subsequent cycles -Day 1,8 and 15 of a 4 week cycle)
Active Comparator: Placebo plus gemcitabine

Drug: gemcitabine hydrochloride
1000 mg/m2 IV weekly (Cycle 1 -Day 1, 8, 15, 22, 29, 36, 43 of an 8 week cycle, Cycle 2 and subsequent cycles -Day 1,8 and 15 of a 4 week cycle)

Outcome Measures

Primary Outcome Measures

  1. Overall survival [3 years]

Secondary Outcome Measures

  1. Progression free survival [3 years]

  2. Quality of Life [3 years]

    Canada, US and selected countries only

  3. Response rates [3 years]

    Complete and partial response only.

  4. Toxicity [3 years]

  5. EGFR levels [3 years]

    Correlate the expression oftissue EGFR levels (at diagnosis) with outcomes and response to treatment

  6. Pharmacokinetics [3 years]

    To measure trough levels of081-774 (Tarceva™) to determine population pharmacokinetics

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 120 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the pancreas

  • Locally advanced or metastatic disease that is considered unresectable

  • No known CNS metastases

PATIENT CHARACTERISTICS:
Age:
  • 18 and over
Performance status:
  • ECOG 0-2
Life expectancy:
  • Not specified
Hematopoietic:

  • Absolute granulocyte count at least 1,500/mm^3

  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin less than 2 times upper limit of normal (ULN)

  • AST and/or ALT less than 2 times ULN (5 times ULN if liver metastases present)

Renal:
  • Creatinine less than 1.5 times ULN
Cardiovascular:

  • No uncontrolled high blood pressure

  • No unstable angina

  • No congestive heart failure

  • No myocardial infarction within the past year

  • No cardiac ventricular arrhythmias requiring medication

Gastrointestinal:

  • No gastrointestinal (GI) tract disease resulting in an inability to take oral medication such as uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

  • No post-surgical malabsorption characterized by:

  • Uncontrolled diarrhea that results in weight loss and vitamin deficiency OR

  • Requires IV hyperalimentation

  • Pancreatic enzyme supplementation allowed provided that the above criteria are not met

Ophthalmic:

  • No ocular inflammation or infection unless fully treated prior to study

  • No significant ophthalmologic abnormalities, including the following:

  • Severe dry eye syndrome

  • Sjogren's syndrome

  • Keratoconjunctivitis sicca

  • Severe exposure keratopathy

  • Disorders that would increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)

Other:

  • Not pregnant or nursing

  • Negative pregnancy test

  • Fertile patients must use effective contraception

  • HIV negative

  • No serious active infection

  • No other serious underlying medical, psychological, or geographical condition that would preclude study participation

  • No prior allergic reaction to compounds with similar chemical or biologic composition to erlotinib

  • No other prior malignancy within the past 5 years except cancer in situ or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:
Biologic therapy:
  • No concurrent biologic therapy or immunotherapy
Chemotherapy:

  • No prior chemotherapy except fluorouracil (with or without leucovorin calcium) or gemcitabine administered concurrently with radiotherapy as a radiosensitizer

  • No other concurrent cytotoxic chemotherapy

Endocrine therapy:
  • Not specified
Radiotherapy:

  • See Chemotherapy

  • At least 4 weeks since prior radiotherapy and recovered

  • Prior radiotherapy for local disease allowed if evidence of disease progression has occurred

  • No concurrent radiotherapy

Surgery:

  • See Disease Characteristics

  • At least 2 weeks since prior major surgery

  • No concurrent ophthalmic surgery

Other:

  • No prior epidermal growth factor receptor inhibitors

  • At least 2 weeks since prior investigational drug

  • No other concurrent investigational drugs during and for at least 30 days after study

  • No other concurrent anti-cancer therapy

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arizona Clinical Research Center Tucson Arizona United States 85712
2 Highlands Oncology Group Springdale Arkansas United States 72764
3 Alta Bates Comprehensive Cancer Center Berkeley California United States 94704
4 Sutter Health West Cancer Research Group Greenbrae California United States 94904
5 Loma Linda University Cancer Institute Loma Linda California United States 92354
6 USC/Norris Comprehensive Cancer Center and Hospital Los Angeles California United States 90033-0804
7 Kenmar Research Institute Los Angeles California United States 90057
8 Century City Hospital Los Angeles California United States 90067
9 David Geffen School of Medicine Los Angeles California United States 90095-7059
10 Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego San Diego California United States 92120
11 Davis, Posteraro, & Wasser, MDs, LLP Manchester Connecticut United States 06040
12 New Britain General Hospital New Britain Connecticut United States 06050-2000
13 Eastern Connecticut Hematology and Oncology Associates Norwich Connecticut United States 06360
14 Hematology Oncology, P.C. Stamford Connecticut United States 06902
15 Florida Cancer Specialists Fort Myers Florida United States 33901
16 Oncology-Hematology Group of South Florida Miami Florida United States 33176
17 Ocala Oncology Center Ocala Florida United States 34471-5563
18 Oncology & Hematology Associates of West Broward Tamarac Florida United States 33321
19 Moffitt Clinic at Tampa General Hospital Tampa Florida United States 33612-9497
20 Central Georgia Hematology Oncology, P.C. Macon Georgia United States 31201
21 Mountain States Tumor Institute Boise Idaho United States 83712
22 Northwest Medical Specialists, P.C. Arlington Heights Illinois United States 60004
23 Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital) Hines Illinois United States 60141
24 Oncology/Hematology Associates of Central Illinois, P.C. Peoria Illinois United States 61602
25 Midwest Cancer Research Group, Inc. Skokie Illinois United States 60076
26 Carle Cancer Center Urbana Illinois United States 61801
27 Medical Consultants Muncie Indiana United States 47304
28 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
29 University of Kansas Medical Center Kansas City Kansas United States 66160-7353
30 Lucille Parker Markey Cancer Center, University of Kentucky Lexington Kentucky United States 40536-0093
31 Norton Healthcare Pavilion Louisville Kentucky United States 40202
32 Mary Bird Perkins Cancer Center Baton Rouge Louisiana United States 70809
33 Metairie Louisiana United States 70006
34 Tulane Cancer Center New Orleans Louisiana United States 70112-2699
35 Annapolis Medical Specialists Annapolis Maryland United States 21401
36 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
37 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231
38 Tuft-New England Medical Center Boston Massachusetts United States 02111
39 St. Elizabeth's Medical Center Boston Massachusetts United States 02135-2997
40 Berkshire Physicians and Surgeons, P.C. Pittsfield Massachusetts United States 01201
41 Baystate Medical Center Springfield Massachusetts United States 01199
42 University of Minnesota Cancer Center Minneapolis Minnesota United States 55455
43 Midwest Oncology Consortium Kansas City Missouri United States 64111
44 New Hampshire Oncology-Hematology PA Hooksett New Hampshire United States 03106
45 St. Barnabas Medical Center Livingston New Jersey United States 07039
46 Hematology-Oncology Associates Mount Holly New Jersey United States 08060
47 Cooper Cancer Institute Voorhees New Jersey United States 08043
48 Cancer Center at Glens Falls Hospital Glens Falls New York United States 12801
49 Arena Oncology Associates Great Neck New York United States 11021
50 NYU School of Medicine's Kaplan Comprehensive Cancer Center New York New York United States 10016
51 Beth Israel Medical Center New York New York United States 10019
52 Interlakes Oncology/Hematology PC Rochester New York United States 14623
53 Staten Island University Hospital Staten Island New York United States 10305
54 University Hospital - Stony Brook Stony Brook New York United States 11794-8174
55 Presbyterian Hospital Charlotte North Carolina United States 28233-3549
56 Mid Dakota Clinic, P.C. Bismarck North Dakota United States 58502-5538
57 University Hospitals of Cleveland Cleveland Ohio United States 44106
58 Earle A. Chiles Research Institute at Providence Portland Medical Center Portland Oregon United States 97213-2967
59 Hematology-Oncology Association of NE Pennsylvania Dunmore Pennsylvania United States 18512
60 University of Pennsylvania Cancer Center Philadelphia Pennsylvania United States 19104
61 Pennsylvania Oncology Hematology Associates Philadelphia Pennsylvania United States 19106
62 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
63 Charleston Hematology-Oncology, P.A. Charleston South Carolina United States 29403
64 Sarah Cannon-Minnie Pearl Cancer Center Nashville Tennessee United States 37203
65 Arlington Cancer Center Arlington Texas United States 76012
66 Southwest Regional Cancer Center Austin Texas United States 78705
67 Texas Cancer Care Fort Worth Texas United States 76104
68 University of Texas - MD Anderson Cancer Center Houston Texas United States 77030-4009
69 Tyler Hematology Oncology, P.A. Tyler Texas United States 75701
70 Green Mountain Oncology Group Bennington Vermont United States 05201
71 Hematology & Oncology Associates of Virginia Mechanicsville Virginia United States 23116
72 Western Washington Oncology Olympia Washington United States 98502
73 Southwest Washington Medical Center Vancouver Washington United States 98664
74 Oncology of Wisconsin Glendale Wisconsin United States 53212
75 Hospital Britanico Buenos Aires Argentina 1280
76 Instituto de Oncologia Angel H. Roffo Buenos Aires Argentina 1417
77 Instituto Alexander Fleming Buenos Aires Argentina 1426
78 Hospital Churruca Buenos Aires Argentina 1437
79 Hospital Italiano Buenos Aires Argentina CP1181ACH
80 Hospital Interzonal De Augudos Euita Lanus Argentina 1824
81 Confidence Medical Center San Isidro Argentina 1642
82 Concord Repatriation General Hospital Concord New South Wales Australia 2139
83 Liverpool Hospital Liverpool New South Wales Australia 2170
84 Newcastle Mater Misericordiae Hospital Newcastle New South Wales Australia NSW 2310
85 Institute of Oncology Randwick New South Wales Australia 2031
86 Royal Adelaide Hospital Adelaide South Australia Australia 5000
87 Ashford Cancer Centre Ashford South Australia Australia 5035
88 Queen Elizabeth Hospital Woodville South Australia Australia 5011
89 Frankston Hospital Frankston Victoria Australia 3199
90 Austin and Repatriation Medical Centre Heidelberg Victoria Australia 3084
91 Royal Perth Hospital Perth Western Australia Australia 6000
92 Peter MacCallum Cancer Institute Melbourne Australia 8006
93 Institut Jules Bordet Brussels Belgium 1000
94 Nucleo de Oncologia da Bahia Bahia Brazil 40170-070
95 Hospital Santa Rita Irtmandade Santa Casa De Porto Alegre Porto Alegre Brazil 91330-490
96 Hospital Israelita Albert Einstein Sao Paulo Brazil 05651-901
97 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
98 British Columbia Cancer Agency - Centre for the Southern Interior Kelowna British Columbia Canada V1Y 5L3
99 Penticton Regional Hospital Penticton British Columbia Canada V2A 3G6
100 British Columbia Cancer Agency - Fraser Valley Cancer Centre Surrey British Columbia Canada V3V 1Z2
101 British Columbia Cancer Agency Victoria British Columbia Canada V8R 6V5
102 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
103 Saint John Regional Hospital Saint John New Brunswick Canada E2L 4L2
104 Newfoundland Cancer Treatment and Research Foundation St. Johns Newfoundland and Labrador Canada A1B 3V6
105 Queen Elizabeth II Health Science Centre Halifax Nova Scotia Canada B3H 2Y9
106 Royal Victoria Hospital, Barrie Barrie Ontario Canada L4M 6M2
107 Cancer Care Ontario-Hamilton Regional Cancer Centre Hamilton Ontario Canada L8V 5C2
108 Kingston Regional Cancer Centre Kingston Ontario Canada K7L 5P9
109 Cancer Care Ontario-London Regional Cancer Centre London Ontario Canada N6A 4L6
110 Credit Valley Hospital Mississauga Ontario Canada L5M 2N1
111 Southlake Regional Health Centre Newmarket Ontario Canada L3Y 2P9
112 Ottawa Regional Cancer Centre Ottawa Ontario Canada K1H 1C4
113 Peterborough Oncology Clinic Peterborough Ontario Canada K9H 7B6
114 Algoma District Medical Group Sault Sainte Marie Ontario Canada P6B 1Y5
115 Hotel Dieu Health Sciences Hospital - Niagara St. Catharines Ontario Canada L2R 5K3
116 Toronto East General Hospital Toronto Ontario Canada M4C 3E7
117 Toronto Sunnybrook Regional Cancer Centre Toronto Ontario Canada M4N 3M5
118 Ontario Cancer Institute Toronto Ontario Canada M4X 1K9
119 Toronto General Hospital Toronto Ontario Canada M4X 1K9
120 Saint Joseph's Health Centre - Toronto Toronto Ontario Canada M6R 1B5
121 Maisonneuve-Rosemont Hospital Montreal Quebec Canada H1T 2M4
122 Hopital Du Sacre-Coeur de Montreal Montreal Quebec Canada H4J 1C5
123 L'Hopital Laval Ste-Foy Quebec Canada G1V 4G5
124 Allan Blair Cancer Centre Regina Saskatchewan Canada S4T 7T1
125 Clinica Las Condes Santiago Chile
126 Pamela Youde Nethersole Eastern Hospital Hong Kong China
127 Queen Mary Hospital Hong Kong China
128 Virchow Klinikum Humboldt Universitaet Berlin Berlin Germany D-13353
129 Universitaetsklinik und Strahlenklinik - Essen Essen Germany D-45122
130 Stadtische Kliniken Frankfurt-Hochst Frankfurt Germany DOH-65929
131 Tumor Biology Center at the Albert - Ludwigs University Freiburg Germany D-79106
132 Martin Luther Universitaet Halle Germany DOH-06112
133 Medizinische Universitaetsklinik und Poliklinik Heidelberg Germany D-69115
134 Universitatsklinik, Saarland Homburg/Saar Germany D-66421
135 University Wurzburg Wurzburg Germany D-97070
136 University Hospital of Heraklion Iraklion (Heraklion) Crete Greece 71110
137 Theagenio Medical Institute Thessaloniki Greece 540 07
138 Hippokration Hospital Thessaloniki Greece 54642
139 Prince of Wales Hospital Shatin, New Territories Hong Kong NT
140 Haemek Medical Center Afula Israel 18101
141 Rambam Medical Center Haifa Israel 31096
142 Rabin Medical Center - Beilinson Campus Petah-Tikva Israel 49100
143 Rabin Medical Center - Golda-Hasharon Campus Petah-Tikva Israel 49372
144 Kaplan Hospital Rehovot Israel 76100
145 Sheba Medical Center Tel Hashomer Israel 52621
146 Tel-Aviv Sourasky Medical Center Tel-Aviv Israel 64239
147 Policlinico - Cattedra di Ematologia Palermo Italy 90100
148 Instituto Nac de Cancerologia Tlalpan Distrito Federal Mexico 22
149 Centro Estatal de Cancerologia Dviango Mexico 34000
150 Auckland Hospital Auckland New Zealand 1
151 Christchurch Hospital Christchurch New Zealand 1
152 Great Poland Cancer Center Poznan Poland 61 866
153 Dolnoslaskie Centrum Oncology Wroclaw Poland 53-413
154 Institute of Oncology - Bucarest Bucarest Romania RO 72435
155 Institutul Oncologic-Universitatea de Medicina Cluj-Napoca Romania 3400
156 St. Spiridon University Hospital Lasi Romania 6600
157 Clinical County Hospital of Sibiu Sibiu Romania 2400
158 National University Hospital Singapore Singapore 119074
159 Singapore General Hospital Singapore Singapore 168609
160 National Cancer Centre - Singapore Singapore Singapore 169610
161 Queen Elizabeth Hospital Birmingham England United Kingdom B18 7QH
162 North Middlesex Hospital Edmonton, London England United Kingdom NI8 1QX
163 St. Luke's Cancer Center Guildford England United Kingdom GU2 5XX
164 Princess Royal Hospital Hull England United Kingdom HU8 9HE
165 Saint Bartholomew's Hospital London England United Kingdom EC1A 7BE
166 Guy's and St. Thomas' Hospitals NHS Trust London England United Kingdom SE1 9RT
167 Christie Hospital N.H.S. Trust Manchester England United Kingdom M20 4BX
168 Northern Centre for Cancer Treatment Newcastle upon Tyne England United Kingdom NE4 6BE
169 Royal South Hants Hospital Southampton England United Kingdom SO14 0YG
170 New Cross Hospital Wolverhampton England United Kingdom WV10 0QP
171 Belfast City Hospital Trust Belfast Northern Ireland United Kingdom BT9 7AB
172 Velindre Hospital Cardiff Wales United Kingdom CF4 7XL
173 Churchill Hospital Oxford United Kingdom OX3 7LJ

Sponsors and Collaborators

  • NCIC Clinical Trials Group

Investigators

  • Study Chair: Malcolm J. Moore, MD, Princess Margaret Hospital, Canada

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00026338
Other Study ID Numbers:
  • PA3
  • CAN-NCIC-PA3
  • OSI-CAN-NCIC-PA3
  • CDR0000069020
First Posted:
Jan 27, 2003
Last Update Posted:
Apr 2, 2020
Last Verified:
Mar 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by NCIC Clinical Trials Group
stage III pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer
Additional relevant MeSH terms:
Pancreatic Neoplasms
Gemcitabine
Erlotinib Hydrochloride

Study Results

No Results Posted as of Apr 2, 2020