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Lapatinib and Epirubicin in Treating Patients With Metastatic Breast Cancer. ICORG 06-30

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ClinicalTrials.gov Identifier: NCT00753207
Recruitment Status : Completed
First Posted : September 16, 2008
Last Update Posted : February 15, 2016
Sponsor:
Information provided by (Responsible Party):
Cancer Trials Ireland

Tracking Information
First Submitted Date  ICMJE September 13, 2008
First Posted Date  ICMJE September 16, 2008
Last Update Posted Date February 15, 2016
Study Start Date  ICMJE October 2007
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2014)
Optimally-tolerated regimen of lapatinib ditosylate in combination with epirubicin hydrochloride [ Time Frame: 2012 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 13, 2008)
Optimally-tolerated regimen of lapatinib ditosylate in combination with epirubicin hydrochloride
Change History Complete list of historical versions of study NCT00753207 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2014)
  • Efficacy of this regimen in terms of objective tumor response rate and disease progression as assessed by standard RECIST criteria [ Time Frame: 2012 ]
  • Pharmacokinetics [ Time Frame: 2012 ]
  • Correlation between baseline expression of intra-tumoral biomarkers (e.g., ErbB1, ErbB2, insulin-like growth factor-1 receptor, p-AKT, and ERK) and clinical response or benefit to lapatinib ditosylate by IHC [ Time Frame: 2012 ]
  • Correlation between expression pattern of drug resistance proteins (e.g., p-glycoprotein, MRP1, BCRP, and MDR-3) and clinical response or benefit to lapatinib ditosylate by IHC [ Time Frame: 2012 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2008)
  • Efficacy of this regimen in terms of objective tumor response rate and disease progression as assessed by standard RECIST criteria
  • Pharmacokinetics
  • Correlation between baseline expression of intra-tumoral biomarkers (e.g., ErbB1, ErbB2, insulin-like growth factor-1 receptor, p-AKT, and ERK) and clinical response or benefit to lapatinib ditosylate by IHC
  • Correlation between expression pattern of drug resistance proteins (e.g., p-glycoprotein, MRP1, BCRP, and MDR-3) and clinical response or benefit to lapatinib ditosylate by IHC
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Lapatinib and Epirubicin in Treating Patients With Metastatic Breast Cancer. ICORG 06-30
Official Title  ICMJE An Open-Label Phase I Study of Fixed Dose Lapatinib in Combination With an Escalating Dose of Epirubicin in Metastatic Breast Cancer
Brief Summary

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with epirubicin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of epirubicin when given together with lapatinib in treating patients with metastatic breast cancer.

Detailed Description

OBJECTIVES:

Primary

  • To assess the safety and tolerability of fixed-dose lapatinib ditosylate in combination with epirubicin hydrochloride in patients with metastatic breast cancer.
  • To determine the optimally-tolerated regimen in these patients.

Secondary

  • To determine the clinical efficacy of this regimen in these patients.
  • To analyze pharmacokinetic data of this regimen.
  • To determine biomarkers that correlate with clinical benefit or response to lapatinib ditosylate in these patients.

Tertiary

  • To identify tumor-derived or blood-derived biomarkers that correlate with or are predictive of clinical response or benefit to lapatinib ditosylate in these patients.
  • To determine the levels of IGF-IR and phosphorylated IGF-IR in tumor tissue.
  • To determine the expression pattern of the proteins associated with drug resistance that may be clinically active in these patients.

OUTLINE: This is a multicenter, dose-escalation study of epirubicin hydrochloride.

Patients receive oral lapatinib ditosylate followed by epirubicin hydrochloride IV over 15-30 minutes on day 1. Treatment repeats every 3 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic analysis via liquid chromatography-mass spectometry (LC-MS).

After completion of study therapy, patients are followed at 28 days and then every 3 months thereafter.

Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: epirubicin hydrochloride
  • Drug: lapatinib ditosylate
  • Other: biomarker analysis
  • Other: immunohistochemistry staining method
  • Other: liquid chromatography
  • Other: mass spectrometry
Study Arms Experimental: Lapatinib and Epirubicin
Fixed dose of lapatinib in combination with escalating dose of epirubicin.
Interventions:
  • Drug: epirubicin hydrochloride
  • Drug: lapatinib ditosylate
  • Other: biomarker analysis
  • Other: immunohistochemistry staining method
  • Other: liquid chromatography
  • Other: mass spectrometry
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 23, 2014)
10
Original Estimated Enrollment  ICMJE
 (submitted: September 13, 2008)
24
Actual Study Completion Date March 2012
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Confirmed diagnosis of breast cancer

    • Metastatic disease
  • No de novo metastasis
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy > 3 months
  • Menopausal status not specified
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 9 g/dL
  • Creatinine clearance ≥ 50 mL/min
  • AST/ALT < 3 times upper limit of the normal (ULN)
  • Total bilirubin normal (unless documented history of congenital hypobilirubinemia)
  • LVEF normal by ECHO or MUGA scan
  • Not pregnant or breastfeeding
  • Negative pregnancy test
  • Fertile patients must use effective contraception from the time of their negative pregnancy test before treatment, during treatment, and 28 days following treatment
  • Able to swallow and retain oral medication
  • History of other malignancies (e.g., cervical carcinoma in situ, melanoma in situ, or basal cell or squamous cell carcinoma of the skin) allowed provided patient has been treated and disease free ≥ 5 years and deemed by the investigator to be at low risk for recurrence
  • No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib ditosylate or excipients
  • No malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
  • No active or uncontrolled infection
  • No known history of uncontrolled or symptomatic angina, arrhythmias, congestive heart failure, or other cardiac disorders
  • No history of prolonged QT interval
  • No active hepatic or biliary disease (except for Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
  • No concurrent disease or condition that would render the patient inappropriate for study participation, or serious medical disorder that would interfere with the patient's safety
  • No dementia, altered mental status, or psychiatric condition that would prohibit the understanding or rendering of informed consent

PRIOR CONCURRENT THERAPY:

  • Prior radiotherapy for treatment of primary tumor allowed
  • Prior non-anthracycline based regimens in neoadjuvant, adjuvant, or metastatic setting allowed
  • Prior adjuvant Herceptin® or ErbB inhibitors allowed provided disease progression was > 6 months after completion of treatment
  • More than 3 months since prior Herceptin®, ErbB1, or ErbB2
  • No prior chemotherapy in the adjuvant or neoadjuvant setting with anthracycline or anthracenedione-containing regimens
  • More than 3 weeks since prior and no concurrent medications that would prolong QT interval
  • More than 1 month or 5 half-lives (whichever is longer) since prior, no concurrent investigational drugs
  • No unresolved or unstable, serious toxicity from prior investigational drug and/or cancer treatment
  • At least 3 weeks since prior and no concurrent prohibited medications (i.e., CYP3A4 inducers or inhibitors)
  • No concurrent non-study anticancer therapy (i.e., chemotherapy, immunotherapy, or biologic therapy)
  • No concurrent participation in another clinical trial
  • No concurrent grapefruit or grapefruit juice
  • Concurrent bisphosphonates allowed
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ireland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00753207
Other Study ID Numbers  ICMJE 06-30 ICORG
ICORG-06-30
ICORG-109403
EUDRACT-2007-002327-33
EU-20875
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Cancer Trials Ireland
Study Sponsor  ICMJE Cancer Trials Ireland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: John Crown, MD St. Vincent's University Hospital
PRS Account Cancer Trials Ireland
Verification Date January 2014

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