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

Phase 2
18 Years
Not Enrolling
Prostate Cancer

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Trial Information

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



- Determine the proportion of patients with hormone-refractory prostate cancer who
experience > 50% decline in PSA after treatment with lapatinib ditosylate.


- Determine the safety of this drug in these patients.

- Determine the time to PSA progression in patients treated with this drug.

- Determine the molecular correlates and predictive biomarkers of response in patients
treated with this drug.

OUTLINE: This is a multicenter, open-label study.

Patients receive oral lapatinib ditosylate once daily. Treatment continues in the absence of
disease progression or unacceptable toxicity.

Serum samples are collected for biomarker analysis at baseline and every 4 weeks.

After completion of study treatment, patients are followed at 4 weeks.

Inclusion Criteria


- 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

- 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


- 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

- 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

- 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)


- 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],

- 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,

- 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)

- 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)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients with early hormone refractory prostate cancer experiencing decrease in measurable disease after treatment with lapatinib (GW572016).

Outcome Description:

Radiographic response will be measured using RECIST criteria for patients with measurable disease every 12 weeks. Subjects will be evaluated for CR (complete response), PR (partial response), SD (stable disease) or PD (progressive disease)

Outcome Time Frame:

Every 12 weeks until disease progression

Safety Issue:


Principal Investigator

Young Whang, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:

LCCC 0505



Start Date:

October 2005

Completion Date:

May 2013

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage I prostate cancer
  • stage II prostate cancer
  • stage III prostate cancer
  • stage IV prostate cancer
  • Prostatic Neoplasms



Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Rex Cancer Center at Rex HospitalRaleigh, North Carolina  27607