Neoplasms, BreastPhase 2NCT00437073
Brain Metastases In ErbB2-Positive Breast Cancer
A Phase 2 study testing capecitabine, topotecan and lapatinib in people with Neoplasms, Breast, run by GlaxoSmithKline at 44 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- capecitabine, topotecan and lapatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 44 sitesin 11 countries
- Study dates
- May 2007to Feb 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 18Show fewer
- 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;
- Women of childbearing potential must have a negative serum pregnancy test at screening and must use an approved contraceptive method, if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product. Males able to father a child must practice adequate methods of birth control or practice complete abstinence from intercourse from the first dose of investigational treatment until one week after the final dose of investigational treatment.
- Subjects must complete all screening assessments as outlined in the protocol;
- Normal organ and marrow function as defined by these LABORATORY VALUES : ANC (absolute neutrophil count) ≥ 1.5 x 10^9/L; Hemoglobin ≥ 10 g/dL (after transfusion if needed); Platelets ≥ 100 x 10^9/L; Albumin ≥ 2.5 g/dL; Serum bilirubin ≤ 1.5x ULN unless due to Gilbert's syndrome; AST and ALT ≤ 5x ULN if documented liver metastases ≤ 3x ULN without liver metastases; Serum Creatinine ≤ 1.2 mg/dL or Calculated Creatinine Clearance1 ≥ 50 mL/min
Who cannot join
- 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;
Show all 31Show fewer
- 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;
- Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel;
- Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety;
- Anticoagulant therapy (other than coumadin or aspirin as catheter prophylaxis) at study entry;
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent, unless a legally acceptable representative could provide informed consent (if in accord with the policies of the local Ethics Committee);
- Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel, CNS vasculitis, or malignant hypertension;
- Active cardiac disease, defined as one or more of the following:
- History of uncontrolled or symptomatic angina
- History of arrhythmias requiring medications, or clinically significant
- Myocardial infarction < 6 months from study entry
- Uncontrolled or symptomatic congestive heart failure
- Ejection fraction below the institutional normal limit
- Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient;
- Uncontrolled infection;
- Pregnant or lactating females;
- History of other malignancy, except for curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. Subjects with other malignancies who have been disease-free for at least 5 years are eligible.
- Have current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
Trial locations and contacts
44 sites in 11 countries.
44 sites in 11 countries
United States13 sites
GSK Investigational Site
Albuquerque, New Mexico, 87131-0001
GSK Investigational Site
Boston, Massachusetts, 02115
GSK Investigational Site
Cary, North Carolina, 27518
GSK Investigational Site
Dallas, Texas, 75230
GSK Investigational Site
Indianapolis, Indiana, 46202
GSK Investigational Site
Minneapolis, Minnesota, 55455
GSK Investigational Site
Philadelphia, Pennsylvania, 19104
GSK Investigational Site
Pittsburgh, Pennsylvania, 15213
GSK Investigational Site
Portland, Oregon, 97239
GSK Investigational Site
Rochester, Minnesota, 55905
GSK Investigational Site
Sioux City, Iowa, 51101-1733
GSK Investigational Site
Spartanburg, South Carolina, 29303
GSK Investigational Site
Washington D.C., District of Columbia, 20007
Spain7 sites
GSK Investigational Site
Barcelona, 08035
GSK Investigational Site
Hospitalet de Llobregat, Barcelona, 08907
GSK Investigational Site
Madrid, 28034
GSK Investigational Site
Madrid, 28041
GSK Investigational Site
Pamplona, 31008
GSK Investigational Site
Santiago de Compostela, 15706
GSK Investigational Site
Valencia, 46010
France5 sites
GSK Investigational Site
Besançon, 25030
GSK Investigational Site
Lille, 59020
GSK Investigational Site
Paris, 75010
GSK Investigational Site
Paris, 75248
GSK Investigational Site
Saint-Herblain, 44805
Germany5 sites
GSK Investigational Site
Bremen, Free Hanseatic City of Bremen, 28205
GSK Investigational Site
Frankfurt am Main, Hesse, 60590
GSK Investigational Site
Munich, Bavaria, 80637
GSK Investigational Site
Munich, Bavaria, 81377
GSK Investigational Site
Troisdorf, North Rhine-Westphalia, 53840
Canada3 sites
GSK Investigational Site
Edmonton, Alberta, T6G 1Z2
GSK Investigational Site
Québec, Quebec, G1S 4L8
GSK Investigational Site
Vancouver, British Columbia, V5Z 4E6
Israel3 sites
GSK Investigational Site
Petah Tikva, 49100
GSK Investigational Site
Ramat Gan, 52621
GSK Investigational Site
Zrifin, 70300
Austria2 sites
GSK Investigational Site
Salzburg, A-5020
GSK Investigational Site
Vienna, A-1090
Greece2 sites
GSK Investigational Site
Heraklion, Crete, 71110
GSK Investigational Site
Neo Faliro, 18547
Italy2 sites
GSK Investigational Site
Milan, Lombardy, 20141
GSK Investigational Site
Perugia, Umbria, 06156
About this study
Official title: Study EGF107671 - a Phase II Study of Lapatinib Plus Topotecan or Lapatinib Plus Capecitabine in the Treatment of Recurrent Brain Metastases From ErbB2-Positive Breast Cancer Following Cranial Radiotherapy
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
- Being tested
- capecitabine, topotecan, lapatinib
- Keywords
- brain metastases, ErbB2, lapatinib, Breast Cancer, HYCAMTIN, topotecan, capecitabine, metastatic breast cancer, TYKERB, XELODA
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
capecitabineDrug
Also called Xeloda
capecitabine 2000mg/m2/day orally, Days 1-14, every 21 days
topotecanDrug
Also called Hycamtin
topotecan intravenous (IV, in the vien) 3.2mg/m2 Days 1, 8 and 15; every 28 days
lapatinibDrug
Also called Tykerb/Tyverb
lapatinib administered 1250mg once daily orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: topotecan; Drug: lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
CNS OR is defined as the number of participants with either a CR or PR as assessed by volumetric analysis of brain MRI and 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. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: 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
Clinical benefit is defined as 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), or stable disease (disease that does not meet CR, PR, or CNS progression criteria) for at least 6 months. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: 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
Non-CNS disease (for par. with measurable baseline non-CNS disease) OR is defined as the number of par. with either a CR or PR as assessed by computed tomography (CT) or MRI scan and RECIST. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough par. enrolled in the study to provide statistically valid analyses.
Measured: 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])
CNS OR is defined as the number of participants with either a CR or PR as assessed by volumetric analysis of brain MRI and 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. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: 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
The site of initial disease will be determined by taking the earliest date of known progression and assigning the appropriate category (CNS or non-CNS) based on the source of the earliest date. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Progression-free Survival
Progression-free survival is defined as the time from the start of treatment until the first documented sign of disease progression at any site or death due to any cause, if sooner. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Overall Survival
Overall survival is defined as the time from the start of treatment until death due to any cause. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: 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 Baseline Tumor-related (TR) Neurological Signs and Symptoms (NSS), Who Experienced Improvement in NSS as Measured by the Neurological Examination Worksheet (NEW)
TR NSS was to be recorded by the Investigator on the NEW, using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE V3.0). Improvement was to be defined as a decrease of 1 or more CTCAE grades from baseline of any TR NSS. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: 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 Disease Stabilization for 6 Months or More
The percentage participants with disease stabiliztion for 6 months or more were defined as those treated participants with a best CNS objective response of SD whose disease stabilization lasted 6 months or more from the start of treatment. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: 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 a >=20% Volumetric Reduction in CNS Lesions
The percentage of participants with a >=20% volumetric reduction in CNS lesions was defined as the percentage of treated participants achieving at least a 20% volumetric reduction in CNS lesions relative to baseline. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.
Measured: Baseline; from the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2007 (estimated)
- Study startMay 2007
- Primary completionJan 2009
- Study completionFeb 2010
Why it stopped: Lapatinib-topotecan arm enrollment closed early per protocol amendment 2. Then enrollment into remaining arm terminated due to operational issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00437073
- Sponsor's protocol ID
- 107671
- Status last verified
- Oct 2012
- First submitted
- 15 Feb 2007
- Last updated
- 15 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 21706359
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study EGF107671 - a Phase II Study of Lapatinib Plus Topotecan or Lapatinib Plus Capecitabine in the Treatment of Recurrent Brain Metastases From ErbB2-Positive Breast Cancer Following Cranial Radiotherapy
- ClinicalTrials.gov ID
- NCT00437073
- Acronym / sponsor ID
- 107671
- Conditions
- Neoplasms, Breast
- Keywords
- brain metastases, ErbB2, lapatinib, Breast Cancer, HYCAMTIN, topotecan, capecitabine, metastatic breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lapatinib-topotecan arm enrollment closed early per protocol amendment 2. Then enrollment into remaining arm terminated due to operational issues.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Jan 2009 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 19 Feb 2007 (estimated)
- Results
- Posted 15 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| lapatinib plus capecitabine | Experimental | Drug: capecitabine, Drug: lapatinibA 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. |
| lapatinib + topotecan | Experimental | Drug: topotecan, Drug: lapatinibA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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;
Key exclusion criteria (31 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| capecitabineAlso: Xelodacapecitabine 2000mg/m2/day orally, Days 1-14, every 21 days | Drug | lapatinib plus capecitabine |
| topotecanAlso: Hycamtintopotecan intravenous (IV, in the vien) 3.2mg/m2 Days 1, 8 and 15; every 28 days | Drug | lapatinib + topotecan |
| lapatinibAlso: Tykerb/Tyverblapatinib administered 1250mg once daily orally | Drug | lapatinib + topotecan, lapatinib plus capecitabine |
Primary outcome
Number of Participants With the Indicated Central Nervous System (CNS) Objective Response (OR)
Time frame: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
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.
Number of Participants With the Indicated CNS Responses
Time frame: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
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.
10 secondary outcomes
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)
Time frame: 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
Time frame: 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
Time frame: 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])
Time frame: 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
Time frame: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Progression-free Survival
Time frame: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Overall Survival
Time frame: 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 Baseline Tumor-related (TR) Neurological Signs and Symptoms (NSS), Who Experienced Improvement in NSS as Measured by the Neurological Examination Worksheet (NEW)
Time frame: 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 Disease Stabilization for 6 Months or More
Time frame: 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 a >=20% Volumetric Reduction in CNS Lesions
Time frame: Baseline; from the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21706359Lin 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.
Related trials for Neoplasms, Breast
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
44 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing capecitabine, topotecan and lapatinib in people with Neoplasms, Breast, run by GlaxoSmithKline at 44 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Spain, France, Germany, Canada and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With the Indicated Central Nervous System (CNS) Objective Response (OR) (time frame: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00437073, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2015.