A Study Evaluating the Efficacy and Safety of Lapatinib + Vinorelbine in ErbB2 Positive Metastatic Breast Cancer Patients

NCT01161368 | Terminated Phase 2 DMC

• 1 other identifier: CECOG/BC.1.2.001
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 2

Brief Summary

The objective of this phase II study is to gain first information on the efficacy (PFS, ORR and OS) and safety of lapatinib plus vinorelbine in patients with HER2 positive metastatic breast cancer pretreated with a combination therapy (chemotherapy and/or hormonal therapy) including lapatinib and presenting with tumor progression. Primary objective is to assess the efficacy with respect to the percentage of patients surviving without disease progression as assessed by RECIST criteria. Secondary objectives are to assess the efficacy of the study treatment with respect to the objective response rates as assessed by RECIST criteria version 1.1, the overall survival and to evaluate the safety profile of the combination by recording the adverse events and abnormal laboratory values associated with the study treatments. The main efficacy endpoints will be investigated both for the intent-to-treat (ITT) population and the per-protocol (PP) population.

Conditions

Metastatic Breast Cancer

Keywords

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progressive Free Survival

  Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  4 years

Secondary Outcomes (2)

• Objective Response Rate using RECIST (vers 1.1)

  4 years

• Overall survival (OS)

  4 years

Study Arms (1)

lapatinib, vinorelbine

EXPERIMENTAL

Drug: Lapatinib, Vinorelbine Lapatinib 1250mg orally once daily continuously plus Vinorelbine 20 mg/m2 intravenously (IV) once weekly \[Days 1 and 8\] for 2 weeks, followed by a rest week in a 3-week cycle.

Drug: Lapatinib, Vinorelbine

Interventions

Lapatinib, Vinorelbine DRUG

Lapatinib 1250mg orally once daily continuously plus Vinorelbine 20 mg/m2 intravenously (IV) once weekly \[Days 1 and 8\] for 2 weeks, followed by a rest week in a 3-week cycle.

lapatinib, vinorelbine

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained prior to any study-specific procedure.
• Females ≥18 years.
• Histologically or cytologically confirmed, HER2-positive (HER+++ or HER++ and FISH positive), adenocarcinoma of the breast with measurable locally recurrent or metastatic disease, who are candidates for chemotherapy. Locally recurrent disease must not be amenable to radiotherapy or resection with curative intent.
• Presence of at least one measurable lesion according to RECIST Criteria version 1.1. (target lesion(s) must not lie within an irradiated area)
• Able to comply with the protocol.
• Prior treatment with a combination therapy including lapatinib as first or second-line treatment for metastatic disease.
• ECOG performance status of 0-1.
• Life expectancy more than 12 weeks.
• Adequate left ventricular ejection function at baseline, defined as LVEF ≥ 50% by either echocardiogram or MUGA.
• Adequate hematological function
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL (may be transfused to maintain or exceed this level).
• Adequate liver function
• Total bilirubin ≤ 1.25 x upper normal limit (ULN)

You may not qualify if:

• Concomitant hormonal therapy for locally recurrent or metastatic disease. Note: previous hormonal therapy is allowed for adjuvant, locally recurrent or metastatic breast cancer, but must have been discontinued at least 1 week prior to first study drug administration.
• Previous radiotherapy for the treatment of metastatic disease (unless given for the relief of metastatic bone pain and with the precautions mentioned below).Radiotherapy administered solely for the relief of metastatic bone pain is allowed prior to study entry, providing that
• not more than 30% of marrow-bearing bone was irradiated
• the last fraction of radiotherapy was administered ≥ 3 weeks prior to first dose of Lapatinib.
• Other primary tumors/hematologic malignancies within the last 5 years, except for adequately controlled limited basal cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Pre-existing peripheral neuropathy NCI CTCAE grade \> 2 at first study drug administration
• Evidence of spinal cord compression or current evidence of central nervous system (CNS) metastases. If suspected, the patient should be scanned by CT or magnetic resonance imaging (MRI) within 28 days prior to first study drug administration to rule out spinal / CNS metastases.
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• History or evidence upon physical/neurological examination of CNS disease unrelated to cancer, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).
• Active infection requiring i.v. antibiotics at first study drug administration.
• Pregnant or lactating females. Pregnancy test to be assessed within 7 days prior to study treatment start.
• Women of childbearing potential (\< 2 years after the last menstruation) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of 6 months following the last administration of study drug.
• Surgery (excluding diagnostic biopsy) within 4 weeks prior to study entry
• Current or recent (within 28 days of first study drug treatment) treatment with another investigational drug or participation in another investigational study
• Clinically significant malabsorption syndrome or inability to take oral medication.

Sponsors & Collaborators

• Central European Cooperative Oncology Group: lead

Study Sites (2)

Dep. of Medicine I , Division of Oncology

Vienna, 1090, Austria

Location

National Institute of Oncology

Budapest, Hungary

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Vinorelbine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Istvan Lang, MD

  National Institute of Oncology Rath Gyorgy u. 7-9. 1122 Budapest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2010
• First Posted: July 13, 2010
• Study Start: September 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: August 13, 2015

Record last verified: 2014-05

Locations

AU (1); HU (1)