Know Cancer

forgot password

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

Phase 1/Phase 2
18 Years
Not Enrolling
Pancreatic Cancer

Thank you

Trial Information

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


Phase I

- Determine the maximum tolerated dose of AZD0530 when given in combination with
gemcitabine in patients with unresectable, locally advanced or metastatic pancreatic

- Determine the safety and tolerability of this regimen in these patients.

- Determine toxicity profile and dose-limiting toxicity of this regimen in these

- Determine pharmacokinetic profile of this regimen in these patients.

- Correlate the toxicity profile with the pharmacokinetics of this regimen in these

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

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


- 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


Performance status

- ECOG 0-2

Life expectancy

- More than 12 weeks


- Platelet count ≥ 100,000/mm^3

- Absolute granulocyte count ≥ 1,500/mm^3


- Bilirubin normal

- AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if clearly
attributable to liver metastasis)


- Creatinine normal


- 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


- No pulmonary disease requiring oxygen supplementation


- 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


- No immune deficiency

- No active, uncontrolled, or serious infection

- No know hypersensitivity to study drugs or their components

- No known HIV positivity


- 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



- 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


- See Disease Characteristics

- See Chemotherapy

- At least 4 weeks since prior radiotherapy for local disease and recovered


- At least 3 weeks since prior major surgery


- 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:


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:


Principal Investigator

Malcolm J. Moore, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Princess Margaret Hospital, Canada


United States: Federal Government

Study ID:




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