A Phase II, Randomised, Multi-Centre Study Evaluating Lapatinib in Combination with Vinorelbine or Capecitabine in Women with ErbB2 Overexpressing Metastatic Breast Cancer

Phase 1

• Conditions: Breast Cancer (with ErbB2 Overexpressing Metastatic Breast Cancer); MedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer

• Registration Number: EUCTR2009-009885-15-GR
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-10-07
• Last Update Posted: 26 September 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 105

Inclusion Criteria

1. Signed informed consent prior to registration.
2. Considered by the investigator to have a life expectancy of =12 weeks.
3. Subjects must be female and have histologically-confirmed invasive breast cancer
with Stage IV disease at primary diagnosis or at relapse after curative-intent surgery. Where the disease is restricted to a solitary lesion, the neoplastic nature of the lesion should be confirmed by cytology or histology.
4. Documented overexpression of ErbB2 by 3+ immunohistochemistry or a positive
score by fluorescence in situ hybridization (FISH) or chromogenic in situ
hybridisation (CISH) using a local laboratory result on a specimen from the primary
tumour or visceral metastatic site. Verification by a central laboratory is not
required.
5. Subjects should have progressive disease following prior therapy which may include anthracyclines, taxanes, and trastuzumab. Subjects who have not received prior treatment for MBC must fulfill one or more of the following conditions: 1) Relapse following receipt of trastuzumab-based therapy in the adjuvant setting, 2)
Contraindication to receiving trastuzumab or documented medical reason for
trastuzumab not being appropriate, as determined by the study investigator, or 3)
Unsuitable for taxane-based chemotherapy as determined by the study investigator.
6. All prior chemotherapy, immunotherapy, biologic therapy, or surgery (except for
minor surgical procedures) must be discontinued or completed at least 4 weeks prior
to first dose of randomized study medication. Hormonal therapy must be
discontinued at least 1 week prior to first dose. Prior treatment with trastuzumab is
permitted provided that at least 6 weeks has elapsed since the last dose of therapy
and all treatment-related adverse events are = Grade 1 at the time of randomization.
7. Prior diagnosis of non-breast cancer is allowed as long as the subject is free of
disease and has not received treatment for prior malignancies for at least 5 years.
Subjects with completely resected basal or squamous cell skin cancer or successfully
treated cervical carcinoma in situ will be allowed if it has been 1 year or longer since
definitive and curative surgery.
8. Females aged =18 years with any menopausal status:
• Non-child-bearing potential (i.e., women with functioning ovaries who have a
current documented tubal ligation or hysterectomy, or women who are
postmenopausal).
• Child-bearing potential (i.e., women with functioning ovaries and no
documented impairment of oviductal or uterine function that would cause
sterility): This category includes women with oligomenorrhea (severe), women
who are perimenopausal, and young women who have begun to menstruate.
These subjects must have a negative serum pregnancy test at screening and
agree to one of the following:
• Complete abstinence from intercourse from 2 weeks prior to
administration of the first dose of study medication until 28 days after
the final dose of study medication; or
• Consistent and correct use of one of the following acceptable methods of
birth control: male partner who is sterile prior to the female subject’s
entry into the study and is the sole sexual partner for that female subject;
any intrauterine device or contraceptive method with a documented
failure rate of less than 1% per year
9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
10. Subjects must have adequate organ and marrow function as defined view protocol for further information.
11. Su

Exclusion Criteria

1. Subjects taking medications listed in Section 5.9.2 of the protocol are not eligible for the study.
This includes human immunodeficiency virus-positive subjects receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with lapatinib.
2. Therapy with lapatinib, vinorelbine, or capecitabine prior to randomization into this
study.
3. Prior therapy with more than one chemotherapeutic regimen for metastatic breast
cancer.
4. Concurrent anticancer or concomitant radiotherapy treatment.
5. History of uncontrolled or symptomatic angina; history of arrhythmias requiring
medications; clinically significant myocardial infarction <6 months from study entry;
uncontrolled or symptomatic congestive heart failure; ejection fraction below the
institutional normal limit; or any other cardiac condition, which in the opinion of the
treating physician, would make this protocol unreasonably hazardous for the patient.
6. Have current active hepatic or biliary disease (with exception of patients with
Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver
disease per investigator assessment).
7. Use of an investigational drug within 30 days or 5 half-lives, whichever is longer,
preceding the first dose of investigational treatment, or, concurrent treatment with an investigational agent or participation in another clinical trial involving
investigational agents.
8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to any of the agents used in this study or their excipients that in
the opinion of the investigator or GSK Medical Monitor contraindicates their
participation.
9. Known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD).
10. Known history of uncontrolled inter-current illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.
11. Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject’s
safety.
12. Pregnant or lactating females at any time during the study (due to the potential
teratogenic or abortifacient effects of lapatinib and breastfeeding).
13. Subjects with diseases affecting gastrointestinal function resulting in an inability to take oral medication, including; malabsorption syndrome, disease significantly
affecting gastrointestinal function, or resection of the stomach, small bowel, or
colon. Subjects with inflammatory bowel disease or ulcerative colitis are also
excluded.
14. Peripheral neuropathy of Grade 2 or greater.
15. Unresolved or unstable, serious toxicity from prior administration of another
investigational drug and/or of prior cancer treatment.
16. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.

Study & Design

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