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.

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

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-22
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

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 age = 18 years old;
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 in conjunction with ErbB2 gene
amplification by FISH, or ErbB2 gene amplification by FISH alone.
7. At least one measurable lesion in the brain, defined as any lesion =10 mm in longest dimension. Measurable brain lesions should not have been treated with prior stereotactic radiosurgery (SRS); an exception being a brain lesion whose longest linear dimension increased = 50% following SRS and whose absolute longest dimension now measures = 15mm;
8. Prior treatment of brain metastases with WBRT and/or SRS;
9. Unequivocal evidence of new and / or progressive lesions in the brain on an imaging study; (view protocol).
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. MUGA
scans will be accepted in cases where an echocardiogram cannot be performed or is
inconclusive;
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, 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.
16. Subjects must complete all screening assessments as outlined in the protocol;
17. Subjects must have normal organ and marrow function as defined (please view 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 Section 7.2 and Section 13.6,
Prohibited Medications;
13. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled
ulcerative colitis are also excluded;
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 o

Study & Design

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