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

NCT00753207 | Completed Phase 1

• 5 other identifiers: 06-30 ICORGICORG-06-30ICORG-109403EUDRACT-2007-002327-33EU-20875
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

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.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (1)

• Optimally-tolerated regimen of lapatinib ditosylate in combination with epirubicin hydrochloride

  2012

Secondary Outcomes (4)

• Efficacy of this regimen in terms of objective tumor response rate and disease progression as assessed by standard RECIST criteria

  2012

• Pharmacokinetics

  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

  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

  2012

Study Arms (1)

Lapatinib and Epirubicin

EXPERIMENTAL

Fixed dose of lapatinib in combination with escalating dose of epirubicin.

Drug: epirubicin hydrochloride; Drug: lapatinib ditosylate; Other: biomarker analysis; Other: immunohistochemistry staining method; Other: liquid chromatography; Other: mass spectrometry

Interventions

epirubicin hydrochloride DRUG

Lapatinib and Epirubicin

lapatinib ditosylate DRUG

Lapatinib and Epirubicin

biomarker analysis OTHER

Lapatinib and Epirubicin

immunohistochemistry staining method OTHER

Lapatinib and Epirubicin

liquid chromatography OTHER

Lapatinib and Epirubicin

mass spectrometry OTHER

Lapatinib and Epirubicin

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (3)

The Adelaide and Meath Hospital, Dublin Incorporating the National Childresn's Hospital

Dublin, 24, Ireland

Location

St Vincent's University Hospital

Dublin, 4, Ireland

Location

St James's Hospital

Dublin, 8, Ireland

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Epirubicin; Lapatinib; Immunohistochemistry; Chromatography, Liquid; Mass Spectrometry

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Chromatography; Chemistry Techniques, Analytical

Study Officials

• John Crown, MD

  St Vincent's University Hospital, Ireland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2008
• First Posted: September 16, 2008
• Study Start: October 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: March 1, 2012
• Last Updated: February 15, 2016

Record last verified: 2014-01

Locations

IE (3)