A Phase I/II Study of AZD0530 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer
18 Years
N/A
Both
Pancreatic Cancer
Trial Information
A Phase I/II Study of AZD0530 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response (complete [CR] and partial response [PR] or stable disease [SD]) at 8 weeks
Outcome Description:
Response is assessed every other cycle and will be reported on at final analysis
Outcome Time Frame:
4 years
Safety Issue:
No
Principal Investigator
Malcolm J. Moore, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Princess Margaret Hospital, Canada
Authority:
United States: Federal Government
Study ID:
I173
NCT ID:
NCT00265876
Start Date:
September 2005
Completion Date:
January 2012
Related Keywords:
- Pancreatic Cancer
- adenocarcinoma of the pancreas
- stage III pancreatic cancer
- recurrent pancreatic cancer
- stage IV pancreatic cancer
- Pancreatic Neoplasms
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