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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00246753
First received: October 28, 2005
Last updated: May 17, 2013
Last verified: May 2013

October 28, 2005
May 17, 2013
October 2005
July 2012   (final data collection date for primary outcome measure)
Proportion of patients with early hormone refractory prostate cancer experiencing decrease in measurable disease after treatment with lapatinib (GW572016). [ Time Frame: Every 12 weeks until disease progression ] [ Designated as safety issue: No ]
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)
- To determine the proportion of patients with early hormone refractory prostate cancer experiencing greater than 50% decline in prostate-specific antigen (PSA) after treatment with GW572016.
Complete list of historical versions of study NCT00246753 on ClinicalTrials.gov Archive Site
  • Number of patients experiencing adverse events [ Time Frame: every 4 weeks of treatment ] [ Designated as safety issue: Yes ]
    Adverse events will be assessed (graded) using CTCAE critera
  • Time to PSA progression [ Time Frame: every 4 weeks of treatment ] [ Designated as safety issue: No ]
    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.
  • Predictive molecular markers in response to treatment with lapatinib (GW572016) [ Time Frame: every 4 weeks of treatment ] [ Designated as safety issue: No ]
    To assess the correlation between expression of molecular markers and patient response to treatment with GW572016
  • - To determine the safety profile of GW572016 in this patient population.
  • - To determine the time to PSA progression in patients treated with GW572016.
  • - To explore the molecular correlates and predictive biomarkers of response to GW572016.
Not Provided
Not Provided
 
Lapatinib in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy
A Phase II Study of Oral Once Daily GW572016 (Lapatinib) In Patients With Hormone Refractory Prostate Cancer

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
Drug: lapatinib ditosylate
1500 mg, daily until disease progression
Other Name: GW572016
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
May 2013
July 2012   (final data collection date for primary outcome measure)

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)
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00246753
LCCC 0505, CDR0000550151
Yes
UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Young Whang, MD, PhD UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP