Last updated: 11/03/2018 09:43:50
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
Brain Metastases In ErbB2-Positive Breast Cancer
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Number of participants with the indicated Central Nervous System (CNS) Objective Response (OR)
Timeframe: 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
Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
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)
Timeframe: 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
Timeframe: 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
Timeframe: 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])
Timeframe: 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
Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Progression-free survival
Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Overall survival
Timeframe: 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)
Timeframe: 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
Timeframe: 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
Timeframe: Baseline; from the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
Interventions:
Drug: capecitabine
Drug: topotecan
Drug: lapatinib
Enrollment:
22
Observational study model:
Not applicable
Primary completion date:
2008-29-12
Time perspective:
Not applicable
Clinical publications:
Lin N, Doering, Eierman, Greil, Campone, Kaufman, Lane S, Zembryki D, Rubin S, Winer E. Randomized Phase II Study of Lapatinib plus Capecitabine or Lapatinib plus Topotecan for Patients with HER2-Positive Breast Cancer Brain Metastases. [J Neurooncol]. 2011;
Medical condition
Neoplasms, Breast
Product
lapatinib, topotecan
Collaborators
Not applicable
Study date(s)
May 2007 to December 2008
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Subjects eligible for enrollment in the study must meet all of the following criteria:
- Signed written informed consent;
- 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
Inclusion and exclusion criteria
Inclusion criteria:
- 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;
- 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
Exclusion criteria:
- 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;
- 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 location(s)
Location
GSK Investigational Site
Hospitalet de Llobregat, Barcelona, Spain, 08907
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Frankfurt am Main, Hessen, Germany, 60590
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Cary, North Carolina, United States, 27518
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Rochester, Minnesota, United States, 55905
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 4E6
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02115
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Troisdorf, Nordrhein-Westfalen, Germany, 53840
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Albuquerque, New Mexico, United States, 87131-0001
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55455
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Edmonton, Alberta, Canada, T6G 1Z2
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Portland, Oregon, United States, 97239
Status
Study Complete
Location
GSK Investigational Site
Muenchen, Bayern, Germany, 81377
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
Status
Study Complete
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20007
Status
Study Complete
Location
GSK Investigational Site
Sioux City, Iowa, United States, 51101-1733
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Dallas, Texas, United States, 75230
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
No longer a GSK study
Actual primary completion date
2008-29-12
Actual study completion date
2008-29-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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