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AZD0530 and Gemcitabine in Locally Advanced/Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery

Primary Purpose

Pancreatic Cancer

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
AZD0530
gemcitabine hydrochloride
Sponsored by
NCIC Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring adenocarcinoma of the pancreas, stage III pancreatic cancer, recurrent pancreatic cancer, stage IV pancreatic cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed pancreatic adenocarcinoma Unresectable disease Locally advanced or metastatic disease Clinically or radiologically documented disease Measurable or evaluable disease (phase I) Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan (phase II) Measurable lesion must be outside of previously irradiated field if it is the sole site of disease unless there is documented disease progression No known brain metastases PATIENT CHARACTERISTICS: Performance status ECOG 0-2 Life expectancy More than 12 weeks Hematopoietic Platelet count ≥ 100,000/mm^3 Absolute granulocyte count ≥ 1,500/mm^3 Hepatic Bilirubin normal AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if clearly attributable to liver metastasis) Renal Creatinine normal Cardiovascular No active cardiomyopathy No congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension No myocardial infarction within the past 12 months Pulmonary No pulmonary disease requiring oxygen supplementation Gastrointestinal Must not require IV hyperalimentation No uncontrolled inflammatory gastrointestinal (GI) disease (e.g., Crohn's disease or ulcerative colitis) No active peptic ulcer disease No postsurgical malabsorption characterized by uncontrolled diarrhea that results in weight loss and vitamin deficiency No other GI tract disease resulting in an inability to take oral medications Must be able to take oral medication without crushing, dissolving, or chewing tablets Pancreatic enzyme supplementation allowed provided the above conditions are met Immunologic No immune deficiency No active, uncontrolled, or serious infection No know hypersensitivity to study drugs or their components No known HIV positivity Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of psychiatric illness (e.g., uncontrolled psychotic disorders) or neurologic disorder that would preclude study compliance No other serious medical condition or illness that would preclude study participation No other malignancy within the past 5 years except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix or bladder PRIOR CONCURRENT THERAPY: Chemotherapy No prior chemotherapy except fluorouracil (with or without leucovorin calcium) or gemcitabine given concurrently with radiotherapy as a radiosensitizer At least 4 weeks since prior fluorouracil or gemcitabine Endocrine therapy Concurrent systemic hormonal therapy for symptom control (e.g., appetite stimulation, pain, or nausea) allowed Radiotherapy See Disease Characteristics See Chemotherapy At least 4 weeks since prior radiotherapy for local disease and recovered Surgery At least 3 weeks since prior major surgery Other At least 2 weeks since prior anticancer therapy or investigational agents The following drugs must not be used for 1-2 weeks before, during, and for 1-2 weeks after completion of study treatment: Ketoconazole Itraconazole Ritonavir Mibefradil Clarithromycin Saquinavir mesylate Indinavir sulfate Erythromycin Nefazodone hydrochloride Fluconazole Diltiazem hydrochloride Alfentanil hydrochloride Carbamazepine Cyclosporine Tacrolimus Lovastatin Simvastatin Any other drug known to be a potent inhibitor of cytochrome 3A4 No other concurrent anticancer therapy or investigational agents

Sites / Locations

  • BCCA - Vancouver Cancer Centre
  • Ottawa Health Research Institute - General Division
  • Algoma District Cancer Program
  • Univ. Health Network-Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AZD0530 + Gemcitabine

Arm Description

Outcomes

Primary Outcome Measures

Response (complete [CR] and partial response [PR] or stable disease [SD]) at 8 weeks
Response is assessed every other cycle and will be reported on at final analysis

Secondary Outcome Measures

Toxicity
Toxicity is assessed from the time of first treatment and final results will be reported at final analysis

Full Information

First Posted
December 14, 2005
Last Updated
August 3, 2023
Sponsor
NCIC Clinical Trials Group
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00265876
Brief Title
AZD0530 and Gemcitabine in Locally Advanced/Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery
Official Title
A Phase I/II Study of AZD0530 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
April 26, 2006 (Actual)
Primary Completion Date
January 8, 2009 (Actual)
Study Completion Date
January 6, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NCIC Clinical Trials Group
Collaborators
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AZD0530 together with gemcitabine may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of AZD0530 when given together with gemcitabine and to see how well they work in treating patients with locally advanced or metastatic pancreatic cancer that cannot be removed by surgery.
Detailed Description
OBJECTIVES: Phase I Determine the maximum tolerated dose of AZD0530 when given in combination with gemcitabine in patients with unresectable, locally advanced or metastatic pancreatic cancer. Determine the safety and tolerability of this regimen in these patients. Determine toxicity profile and dose-limiting toxicity of this regimen in these patients. Determine pharmacokinetic profile of this regimen in these patients. Correlate the toxicity profile with the pharmacokinetics of this regimen in these patients. Phase II Determine the objective response rate (partial and complete response) and prolonged stable disease rate in patients treated with this regimen. Determine the median survival, 1-year survival, response or stable disease duration, time to disease progression, clinical benefit response, and progression-free survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. Correlate changes in serum CTX levels (post-treatment vs baseline) with response and other clinical outcomes in patients treated with this regimen. OUTLINE: This is a phase I, open-label, multicenter, dose-escalation study of AZD0530 followed by a phase II study. Phase I: Patients receive oral AZD0530 once daily on days 1-28 and gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive 2 additional courses after achieving complete response or stable partial response. Patients with ongoing stable disease receive up to 6 courses. Patients who discontinue gemcitabine due to unacceptable toxicity or who complete 6 courses of therapy may continue to receive AZD0530 alone in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of AZD0530 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. Phase II: Patients receive AZD0530 at the MTD determined in phase I and gemcitabine as in phase I. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
adenocarcinoma of the pancreas, stage III pancreatic cancer, recurrent pancreatic cancer, stage IV pancreatic cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AZD0530 + Gemcitabine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AZD0530
Intervention Description
Taken daily every 4 weeks
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Description
1000mg/m2 IV weekly
Primary Outcome Measure Information:
Title
Response (complete [CR] and partial response [PR] or stable disease [SD]) at 8 weeks
Description
Response is assessed every other cycle and will be reported on at final analysis
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Toxicity
Description
Toxicity is assessed from the time of first treatment and final results will be reported at final analysis
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed pancreatic adenocarcinoma Unresectable disease Locally advanced or metastatic disease Clinically or radiologically documented disease Measurable or evaluable disease (phase I) Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan (phase II) Measurable lesion must be outside of previously irradiated field if it is the sole site of disease unless there is documented disease progression No known brain metastases PATIENT CHARACTERISTICS: Performance status ECOG 0-2 Life expectancy More than 12 weeks Hematopoietic Platelet count ≥ 100,000/mm^3 Absolute granulocyte count ≥ 1,500/mm^3 Hepatic Bilirubin normal AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if clearly attributable to liver metastasis) Renal Creatinine normal Cardiovascular No active cardiomyopathy No congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension No myocardial infarction within the past 12 months Pulmonary No pulmonary disease requiring oxygen supplementation Gastrointestinal Must not require IV hyperalimentation No uncontrolled inflammatory gastrointestinal (GI) disease (e.g., Crohn's disease or ulcerative colitis) No active peptic ulcer disease No postsurgical malabsorption characterized by uncontrolled diarrhea that results in weight loss and vitamin deficiency No other GI tract disease resulting in an inability to take oral medications Must be able to take oral medication without crushing, dissolving, or chewing tablets Pancreatic enzyme supplementation allowed provided the above conditions are met Immunologic No immune deficiency No active, uncontrolled, or serious infection No know hypersensitivity to study drugs or their components No known HIV positivity Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of psychiatric illness (e.g., uncontrolled psychotic disorders) or neurologic disorder that would preclude study compliance No other serious medical condition or illness that would preclude study participation No other malignancy within the past 5 years except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix or bladder PRIOR CONCURRENT THERAPY: Chemotherapy No prior chemotherapy except fluorouracil (with or without leucovorin calcium) or gemcitabine given concurrently with radiotherapy as a radiosensitizer At least 4 weeks since prior fluorouracil or gemcitabine Endocrine therapy Concurrent systemic hormonal therapy for symptom control (e.g., appetite stimulation, pain, or nausea) allowed Radiotherapy See Disease Characteristics See Chemotherapy At least 4 weeks since prior radiotherapy for local disease and recovered Surgery At least 3 weeks since prior major surgery Other At least 2 weeks since prior anticancer therapy or investigational agents The following drugs must not be used for 1-2 weeks before, during, and for 1-2 weeks after completion of study treatment: Ketoconazole Itraconazole Ritonavir Mibefradil Clarithromycin Saquinavir mesylate Indinavir sulfate Erythromycin Nefazodone hydrochloride Fluconazole Diltiazem hydrochloride Alfentanil hydrochloride Carbamazepine Cyclosporine Tacrolimus Lovastatin Simvastatin Any other drug known to be a potent inhibitor of cytochrome 3A4 No other concurrent anticancer therapy or investigational agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Malcolm J. Moore, MD
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Sharlene Gill, MD
Organizational Affiliation
British Columbia Cancer Agency
Official's Role
Study Chair
Facility Information:
Facility Name
BCCA - Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Ottawa Health Research Institute - General Division
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Algoma District Cancer Program
City
Sault Ste. Marie
State/Province
Ontario
ZIP/Postal Code
P6B 0A8
Country
Canada
Facility Name
Univ. Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21170669
Citation
Renouf DJ, Moore MJ, Hedley D, Gill S, Jonker D, Chen E, Walde D, Goel R, Southwood B, Gauthier I, Walsh W, McIntosh L, Seymour L. A phase I/II study of the Src inhibitor saracatinib (AZD0530) in combination with gemcitabine in advanced pancreatic cancer. Invest New Drugs. 2012 Apr;30(2):779-86. doi: 10.1007/s10637-010-9611-3. Epub 2010 Dec 18.
Results Reference
result

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AZD0530 and Gemcitabine in Locally Advanced/Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery

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