A Phase II Study of Oral Once Daily GW572016 (Lapatinib) In Patients With Hormone Refractory Prostate Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate

- Hormone-refractory disease

- Prior androgen-deprivation therapy (either bilateral orchiectomy or medical
castration resulting in a testosterone level < 50 ng/dL) for prostate cancer
required

- Biochemical progression on androgen-deprivation therapy with rising PSA,
defined as elevated PSA (≥ 5 ng/mL) that has risen serially from baseline
on 2 occasions ≥ 1 week apart

- No known brain metastases

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy > 12 weeks

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Cardiac ejection fraction normal by ECHO or MUGA

- Fertile patients must use effective contraception

- Able to swallow and retain oral medication

- No history of allergic reaction to compounds of similar chemical or biological
composition to lapatinib ditosylate

- No other concurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia

- No psychiatric illness or social situation that would limit study compliance

- No HIV positivity

- No gastrointestinal (GI) tract disease resulting in an inability to take oral
medication

- No malabsorption syndrome

- No requirement for IV alimentation

- No uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

- No current active hepatic or biliary disease (with the exception of patients with
Gilbert syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver
disease per investigator assessment)

PRIOR CONCURRENT THERAPY:

- Recovered from all prior therapies

- No prior chemotherapy for prostate cancer

- No prior or concurrent cytotoxic chemotherapy

- At least 4 weeks since prior anti-androgen therapy, including flutamide (6 weeks for
bicalutamide and nilutamide)

- At least 4 weeks since prior radiotherapy

- At least 4 weeks since prior surgery

- At least 4 weeks since other prior hormonal therapy, including ketoconazole,
megestrol acetate, and aminoglutethimide

- At least 4 weeks since other prior chemotherapy

- At least 4 weeks since prior investigational agents

- At least 7 days since prior and no concurrent inhibitors of CYP3A4, including any of
the following:

- Antibiotics (clarithromycin, erythromycin, troleandomycin)

- Antifungals (itraconazole, ketoconazole, fluconazole [> 150 mg daily],
voriconazole)

- Antiretrovirals or protease inhibitors (delavirdine, nelfinavir, amprenavir,
ritonavir, indinavir, saquinavir, lopinavir)

- Calcium channel blockers (verapamil, diltiazem)

- Antidepressants (nefazodone, fluvoxamine)

- Gastrointestinal agents (cimetidine, aprepitant)

- Grapefruit or grapefruit juice

- At least 6 months since prior and no concurrent amiodarone

- At least 14 days since prior and no concurrent herbal or dietary supplements

- At least 14 days since prior and no concurrent inducers of CYP3A4, including any of
the following:

- Antibiotics (all rifamycin class agents [e.g., rifampicin, rifabutin,
rifapentine])

- Anticonvulsants (phenytoin, carbamazepine, barbiturates [e.g., phenobarbital])

- Antiretrovirals (efavirenz, nevirapine)

- Glucocorticoids (cortisone [> 50 mg], hydrocortisone [> 40 mg], prednisone [> 10
mg], methylprednisolone [> 8 mg], dexamethasone [> 1.5 mg])

- Daily oral glucocorticoid doses ≤ 1.5 mg of dexamethasone (or equivalent)
allowed

- Hypericum perforatum (St. John's wort)

- Modafinil

- No prior ErbB family-targeting therapies

- No prior surgical procedures affecting absorption

- No concurrent local radiotherapy for pain control or life-threatening situations
(i.e., spinal cord compression, superior vena cava syndrome)