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

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