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

• Conditions: Brain metastases from ErbB2-positive breast cancer; MedDRA version: 8.1Level: LLTClassification code 10006128Term: Brain metastases

• Registration Number: EUCTR2006-005912-28-IE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-06
• Last Update Posted: 30 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

Subjects eligible for enrollment in the study must meet all of the following criteria:

1. Signed written informed consent;
2. Females or males of 18 years of age or older;
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1;
4. Life expectancy of at least 12 weeks;
5. Subjects must have histologically or cytologically confirmed invasive breast cancer, with Stage IV disease;
6. ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC with ErbB 2 gene amplification by FISH, or ErbB 2 gene amplification by FISH alone;
7. At least one measurable lesion in the brain, defined as any lesion of 10mm or greater in longest dimension. Measurable brain lesions should not have been treated with prior stereotactic radiosurgery (SRS);
8. Prior treatment of brain metastases with whole-brain radiotherapy and/or SRS;
9. Evidence of new and / or progressive lesions in the brain;
Note: Subjects with progressive brain lesions are not required to meet RECIST criteria for CNS progression in order to be eligible for this study.
10. 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;
11. 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;
12. 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;
13. At least 3 weeks since major surgical procedures;
14. Able to swallow and retain oral medications;
15. Women of childbearing potential must have a negative serum pregnancy test at screening and must use an approved contraceptive method, 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.
16. Subjects must complete all screening assessments as outlined in the protocol;
17. Subjects must have normal organ and marrow function (as defined in the protocol).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:

1. 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;
2. Concurrent treatment with an investigational agent or participation in another treatment clinical trial;
3. Prior therapy with a topoisomerase 1 inhibitor;
4. Prior lapatinib therapy;
5. Prior therapy with capecitabine;
6. Known dihydropyrimidine dehydrogenase (DPD) deficiency;
7. ECOG Performance Status 2 or greater;
8. 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;
9. Subjects with evidence of leptomeningeal carcinomatosis at screening;
10. History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib;
11. History of allergic reactions attributed to compounds chemically related to capecitabine, fluorouracil or any excipients;
12. Concurrent treatment with medications listed in the protocol;
13. Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or active, uncontrolled ulcerative colitis;
14. History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast;
15. Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel;
16. 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;
17. Anticoagulant therapy at study entry (other than coumadin or aspirin as catheter prophylaxis, or a low dose heparin [i.e. 50 unit unfractionated] flush of a central venous device);
18. 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);
19. Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel, CNS vasculitis, or malignant hypertension;
20. 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;
21. Uncontrolled infection;
22. Pregnant or lactating females;
23. 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 disea

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified