Efficacy Study of Single Agent Trastuzumab or Lapatinib to Treat HER2-Overexpressing Breast Cancer (HERLAP)

A Phase II, Randomized Trial With Single Agent Trastuzumab or Lapatinib in Patients With Metastatic HER2-Overexpressing Breast Cancer

This study will evaluate the activity of single agent trastuzumab or lapatinib in patients not previously treated for HER-2 positive (FISH positive) metastatic breast cancer. A companion biological study will assess factors correlated with sensitivity or resistance to either one of the compounds

Study Overview

• Status: Unknown
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab or Lapatinib

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Filippo Montemurro, MD; Phone Number: 278 +39.011.9933; Email: fmontemurro@mauriziano.it
• Study Contact Backup: Name: Manuela Muliello, Study Coordinator; Phone Number: 278 +39.011.9933; Email: mmuliello@mauriziano.it

Study Locations

• Italy
  • Candiolo , Torino, Italy, 10060
    • Recruiting
    • Institute for Cancer Research and Treatment (I.R.C.C.)
  • Cuneo, Italy, 12100
    • Active, not recruiting
    • U.O. Oncologia Medica
  • Torino, Italy, 10126
    • Active, not recruiting
    • U.O. Oncologia Medica - COES Molinette
  • Torino
    • Orbassano, Torino, Italy, 10043
      • Active, not recruiting
      • U.O. Oncologia Medica - Ospedale San Luigi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women aged 18-75 years
• Histologically or cytologically confirmed metastatic disease.
• HER2-Overexpression proven by Fluorescence in Situ Hybridization (FISH).
• Availability of paraffin-embedded block of either primitive tumor and/or biopsy of metastases.
• No prior chemotherapy for metastatic or locally advanced disease. Patients with hormone receptor (oestrogen and/or progesterone) positive breast cancer can be eligible provided that they had received only ONE line of hormonal therapy for metastatic disease.
• For patients undergoing hormonal therapy for metastatic disease, disease progression must be confirmed according to RECIST criteria.
• At least 20% increase in the sum of longest diameters, OR
• Evidence of new metastatic lesions or progression of pre-existing non-target lesions.
• Presence of at least one monodimensionally measurable lesion. Patients without clinically or radiologically proven evidence of disease are not eligible.
• Patients with exclusively skin disease are eligible, provided that the disease evolution under treatment can be photographically documented.

• Patients with involvement of NCS, besides presence of measurable lesions, are eligible provided that:

  • Brain lesion/s has/have been radically resected;
  • Brain lesion/s has/have obtained complete remission following radiation therapy. Complete remission must be documented by TC or RMN.
• At least 4-week interval from end of radiotherapy, hormono- or immunotherapy and enrollment in this study.
• ECOG PS </= 2 and life expectancy of at least 6 months.
• Liver metastases involving < 30% of liver volume.
• Adequate hematopoietic, liver and renal function
• Written informed consent.
• Patients with childbearing potential must have negative pregnancy test and must use adequate contraceptive measures during treatment.
• Prior treatment with Trastuzumab as adjuvant therapy is permitted provided that it was completed at least 12 months prior enrollment in this study.

Exclusion Criteria:

• Prior chemotherapy for metastatic disease.
• Active pregnancy or breastfeeding.
• Previous treatment with Lapatinib.
• Previous therapy with mono- or policlonal antibodies for metastatic disease.
• Patients with bone involvement or pleural effusion/ascites as unique localization of disease.
• Patients with dyspnea due to presence of disease (lymphangitis) or requiring oxygen therapy.
• Patients with clinically evident hearth disease and/or active infectious diseases.
• Patients with not resected or not irradiated brain and/or leptomeningeal metastases.
• Prior or actual concurrent neoplasms, with the exception of adequately treated carcinoma della cervice uterina and basal cell or squamocellular carcinoma of the skin.
• Patients with uncontrolled serious illnesses that may compromise the compliance of the patient to the treatment.
• Previous allergic reactions towards any excipient in the composition of Trastuzumab or Lapatinib.
• Use of any experimental drug within 4 weeks prior initiation of study treatment.
• Women with childbearing potential who refuse to use adequate contraceptive measures.
• Patients unable to give written informed consent or are not compliant with treatment.
• Patients with great tumor involvement (> 30% dof hepatic volume, etc).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 - Trastuzumab; Day1 Week1: 8 mg/kg iv in 90 min. Following 1st week: 2 mg/kg once/weekly for 8 weeks	Drug: Trastuzumab or Lapatinib; Trastuzumab: loading dose 8 mg/kg iv in 90 min.followed by weekly doses of 2 mg/kg Lapatinib: 1500 mg/die orally
Experimental: 2 - Lapatinib; 1500 mg/die orally	Drug: Trastuzumab or Lapatinib; Trastuzumab: loading dose 8 mg/kg iv in 90 min.followed by weekly doses of 2 mg/kg Lapatinib: 1500 mg/die orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evidence of clinically definite response confirmed by CT or MRI	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Progression (TTP) and duration of response in patients treated with Trastuzumab	8 weeks

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Ordine Mauriziano di Torino
• Investigators: Study Chair: Massimo Aglietta, Full Professor, MD, University of Turin Medical School at AO Ordine Mauriziano di Torino; Principal Investigator: Filippo Montemurro, MD, AO Ordine Mauriziano di Torino

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Anticipated): December 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: February 11, 2009
• First Submitted That Met QC Criteria: February 11, 2009
• First Posted (Estimate): February 12, 2009

Study Record Updates

• Last Update Posted (Estimate): June 26, 2009
• Last Update Submitted That Met QC Criteria: June 25, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: breast cancer; HER2; Trastuzumab; Lapatinib; HER2 gene-amplification
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Trastuzumab; Lapatinib
• Other Study ID Numbers: 20080331 - HERLAP; EudraCT No: 2008-001916-18