Brain Metastases In ErbB2-Positive Breast Cancer

NCT00437073 | Terminated Phase 2 Results

• 1 other identifier: 107671
• Study Type: interventional
• Target: 22
• Locations: 11 countries
• Sites: 44

Brief Summary

This study is for patients with ErbB2 overexpressing breast cancer that has spread to the brain and is still progressing there even after radiation treatment using WBRT (whole brain radiotherapy) or SRS (stereotactic radiosurgery) to the brain. The study will determine how safe and effective lapatinib is when given in combination with capecitabine to treat patients with ErbB2 overexpressing breast cancer that has spread to the brain. Lapatinib is an oral drug that will be taken every day. Tests for safety and efficacy will be performed regularly during the course of the study.

Conditions

Neoplasms, Breast

Keywords

brain metastases; ErbB2; lapatinib; Breast Cancer; HYCAMTIN; topotecan; capecitabine; metastatic breast cancer; TYKERB; XELODA

Outcome Measures

Primary Outcomes (2)

• Number of Participants With the Indicated Central Nervous System (CNS) Objective Response (OR)

  CNS OR is defined as the number of participants with either a complete response (CR) or partial response (PR) as assessed by volumetric analysis of brain magnetic resonance imaging (MRI) and Response Evaluation Criteria In Solid Tumors (RECIST). CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =\>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline.

  From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

• Number of Participants With the Indicated CNS Responses

  CNS responses were assessed by volumetric (V) analysis of brain MRI and RECIST. CR: complete resolution of all evaluable and non-evaluable brain metastases (BMs). PR: =\>50% reduction in the V sum of all evaluable BMs compared to baseline. A response of "Other" was used for participants who discontinued the study prior to the first efficacy assessment. Stable Disease (SD): disease that does not meet CR, PR, or CNS progression criteria. Progressive disease (PD): a requirement for a new steroid or an increasing steroid dose for the treatment of worsening neurological signs/symptoms due to BMs.

  From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Secondary Outcomes (10)

• Duration of CNS Objective Response (Defined as the Time From the First Documented Evidence of CNS PR or CR Until the First Documented Sign of Disease Progression or Death, if Sooner)

  From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

• Percentage of Participants With Clinical Benefit

  From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

• Percentage of Participants (Par.) With Objective Response by RECIST in Non-CNS Disease

  From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

• Time to CNS Objective Response (Defined as the Time From the Start of Treatment Until the First Documented Evidence of Partial or Complete Tumor Response [Whichever Status is Recorded First])

  From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

• Number of Participants With the Indicated Site of Initial Disease Progression

  From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Study Arms (2)

lapatinib plus capecitabine

EXPERIMENTAL

A total of 55 isubjects will be enrolled into this arm. Subjects with progression of CNS and/or non-CNS disease will be considered progressors. At the time of radiographically-documented CNS and/or non-CNS disease progression, a subject randomized to this arm will be allowed to cross over to the alternative arm.

Drug: capecitabine; Drug: lapatinib

lapatinib + topotecan

EXPERIMENTAL

A total of 55 isubjects will be enrolled into this arm. Subjects with progression of CNS and/or non-CNS disease will be considered progressors. At the time of radiographically-documented CNS and/or non-CNS disease progression, a subject randomized to this arm will be allowed to cross over to the alternative arm.

Drug: topotecan; Drug: lapatinib

Interventions

capecitabine DRUG

capecitabine 2000mg/m2/day orally, Days 1-14, every 21 days

Also known as: Xeloda

lapatinib plus capecitabine

topotecan DRUG

topotecan intravenous (IV, in the vien) 3.2mg/m2 Days 1, 8 and 15; every 28 days

Also known as: Hycamtin

lapatinib + topotecan

lapatinib DRUG

lapatinib administered 1250mg once daily orally

Also known as: Tykerb/Tyverb

lapatinib + topotecan; lapatinib plus capecitabine

Eligibility Criteria

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

You may qualify if:

• Subjects eligible for enrollment in the study must meet all of the following criteria:
• Signed written informed consent;
• Females or males age ≥ 18 years old;
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1;
• Life expectancy of at least 12 weeks;
• Subjects must have histologically or cytologically confirmed invasive breast cancer, with Stage IV disease;
• ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB 2 gene amplification by FISH, or ErbB 2 gene amplification by FISH alone (in subjects whose tumor blocks were not assessed by IHC). Subjects with tumors that are 2+ by IHC but negative or borderline by FISH assay are ineligible. For subjects with a history of more than one primary breast cancer, each breast cancer must be ErbB2 overexpressing to be eligible;
• ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB2 gene amplification by FISH, or ErbB2 gene amplification by FISH alone (in subjects whose tumor blocks were not assessed by IHC). ErbB2 gene amplification is defined by: \> 6 ErbB2 gene copies/nucleus for test systems without an internal control probe or an ErbB2/CEP 17 ratio of more than 2.2. Subjects with tumors that are 2+ by IHC but negative or borderline by FISH assay are ineligible. For subjects with a history of more than one primary breast cancer, each breast cancer must be ErbB2 overexpressing to be eligible;
• Prior treatment of brain metastases with WBRT and/or SRS;
• Unequivocal evidence of new and / or progressive lesions in the brain on an imaging study; Note: Subjects with progressive brain lesions are not required to meet RECIST criteria for CNS progression in order to be eligible for this study.
• Prior treatment with trastuzumab, either alone or in combination with chemotherapy is required. Trastuzumab will be discontinued at least 2 weeks prior to enrollment on study;
• Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. Subjects who require cardiac medications (e.g. positive inotropic agents or afterload reducers) for normal ejection fraction are ineligible. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive;
• At least 2 weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, or hormonal therapy for cancer, and sufficiently recovered or stabilized from side effects associated with prior therapy. Concurrent treatment with bisphosphonates is permitted;
• At least 3 weeks since major surgical procedures;
• Able to swallow and retain oral medications;

You may not qualify if:

• Subjects meeting any of the following criteria must not be enrolled in the study:
• Subjects who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or who have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
• Concurrent treatment with an investigational agent or participation in another treatment clinical trial;
• Prior therapy with a topoisomerase 1 inhibitor;
• Prior lapatinib therapy;
• Prior therapy with capecitabine;
• Known dihydropyrimidine dehydrogenase (DPD) deficiency;
• ECOG Performance Status 2 or greater;
• Subjects receiving concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of their cancer. Hormone therapy for ovarian suppression which has been used for \> 6 months, during which time there has been disease progression in the brain, is allowed. Concurrent treatment with bisphosphonates is allowed;
• Subjects with evidence of leptomeningeal carcinomatosis at screening;
• History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib;
• History of allergic reactions attributed to compounds chemically related to capecitabine, fluorouracil or any excipients;
• Concurrent treatment with medications listed as Prohibited Medications;
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded;
• History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast;

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (44)

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

Sioux City, Iowa, 51101-1733, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02115, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55455, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

Albuquerque, New Mexico, 87131-0001, United States

Location

GSK Investigational Site

Cary, North Carolina, 27518, United States

Location

GSK Investigational Site

Portland, Oregon, 97239, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Salzburg, A-5020, Austria

Location

GSK Investigational Site

Vienna, A-1090, Austria

Location

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Vancouver, British Columbia, V5Z 4E6, Canada

Location

GSK Investigational Site

Québec, Quebec, G1S 4L8, Canada

Location

GSK Investigational Site

Besançon, 25030, France

Location

GSK Investigational Site

Lille, 59020, France

Location

GSK Investigational Site

Paris, 75010, France

Location

GSK Investigational Site

Paris, 75248, France

Location

GSK Investigational Site

Saint-Herblain, 44805, France

Location

GSK Investigational Site

Munich, Bavaria, 80637, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81377, Germany

Location

GSK Investigational Site

Bremen, City state Bremen, 28205, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

Location

GSK Investigational Site

Troisdorf, North Rhine-Westphalia, 53840, Germany

Location

GSK Investigational Site

Heraklion, Crete, 71110, Greece

Location

GSK Investigational Site

Neo Faliro, 18547, Greece

Location

GSK Investigational Site

Petah Tikva, 49100, Israel

Location

GSK Investigational Site

Ramat Gan, 52621, Israel

Location

GSK Investigational Site

Zrifin, 70300, Israel

Location

GSK Investigational Site

Milan, Lombardy, 20141, Italy

Location

GSK Investigational Site

Perugia, Umbria, 06156, Italy

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Pamplona, 31008, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Valencia, 46010, Spain

Location

GSK Investigational Site

Uppsala, SE-751 85, Sweden

Location

Related Publications (1)

• Lin NU, Eierman W, Greil R, Campone M, Kaufman B, Steplewski K, Lane SR, Zembryki D, Rubin SD, Winer EP. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neurooncol. 2011 Dec;105(3):613-20. doi: 10.1007/s11060-011-0629-y. Epub 2011 Jun 26.

  PMID: 21706359 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

Capecitabine; Topotecan; Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: May 1, 2007
• Primary Completion: January 1, 2009
• Study Completion: February 1, 2010
• Last Updated: October 15, 2015
• Results First Posted: October 15, 2012

Record last verified: 2012-10

Locations

IL (3); CA (3); GR (2); FR (5); DE (5); IT (2); ES (7); AU (2); BE (1); US (13); SE (1)