Lapatinib in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

Prostate Cancer Clinical Trial

— NRR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00246753
• Other study ID #: LCCC 0505
• Secondary ID: CDR0000550151
• Status: Completed
• Phase: Phase 2
• First received: October 28, 2005
• Last updated: January 20, 2016
• Start date: October 2005
• Est. completion date: May 2013

Study information

• Verified date: January 2016
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well lapatinib works in treating patients with prostate cancer that did not respond to hormone therapy.

Description:

OBJECTIVES:

Primary

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

Secondary

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: May 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• lapatinib ditosylate
1500 mg, daily until disease progression

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with early hormone refractory prostate cancer experiencing decrease in measurable disease after treatment with lapatinib (GW572016).	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)	Every 12 weeks until disease progression	No
Secondary	Number of patients experiencing adverse events	Adverse events will be assessed (graded) using CTCAE critera	every 4 weeks of treatment	Yes
Secondary	Time to PSA progression	Efficacy monitoring will be assessed by serum PSA for those subjects without radiographic, measurable disease. Decrease in PSA value from baseline by > 50 % for 2 successive evaluations at least 4 weeks apart will be considered PSA repsonse.	every 4 weeks of treatment	No
Secondary	Predictive molecular markers in response to treatment with lapatinib (GW572016)	To assess the correlation between expression of molecular markers and patient response to treatment with GW572016	every 4 weeks of treatment	No