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

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00265876

Collaborator

AstraZeneca (Industry)

Enrollment

Locations

Arm

77.6

Actual Duration (Months)

8.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: AZD0530 Drug: gemcitabine hydrochloride	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Study of AZD0530 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer

Actual Study Start Date :

Jul 19, 2005

Actual Primary Completion Date :

Jan 8, 2009

Actual Study Completion Date :

Jan 6, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD0530 + Gemcitabine	Drug: AZD0530 Taken daily every 4 weeks Drug: gemcitabine hydrochloride 1000mg/m2 IV weekly

Arm

Intervention/Treatment

Experimental: AZD0530 + Gemcitabine

Drug: AZD0530

Taken daily every 4 weeks

Drug: gemcitabine hydrochloride

1000mg/m2 IV weekly

Outcome Measures

Primary Outcome Measures

Response (complete [CR] and partial response [PR] or stable disease [SD]) at 8 weeks [4 years]
Response is assessed every other cycle and will be reported on at final analysis

Secondary Outcome Measures

Toxicity [4 years]
Toxicity is assessed from the time of first treatment and final results will be reported at final analysis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
2	Ottawa Health Research Institute - General Division	Ottawa	Ontario	Canada	K1H 8L6
3	Algoma District Cancer Program	Sault Ste. Marie	Ontario	Canada	P6B 0A8
4	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9