A Phase 3 Randomized Open Label Study of Neratinib versus Lapatinib plus Capecitabine for the Treatment of ErbB-2 Positive Locally Advanced or Metastatic Breast Cancer - Not available

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2008-005425-11-NL
• Date of registration: 12/06/2009
• Prospective Registration: Yes
• Primary sponsor: Wyeth Research
• Public title: A Phase 3 Randomized Open Label Study of Neratinib versus Lapatinib plus Capecitabine for the Treatment of ErbB-2 Positive Locally Advanced or Metastatic Breast Cancer - Not available
• Scientific title: A Phase 3 Randomized Open Label Study of Neratinib versus Lapatinib plus Capecitabine for the Treatment of ErbB-2 Positive Locally Advanced or Metastatic Breast Cancer - Not available
• Date of first enrolment: 28/12/2009
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005425-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, France, Germany, Greece, Hungary, Italy, Netherlands, Slovenia, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Women aged at least 18 years.

2. Histologically and/or cytologically confirmed diagnosis of breast cancer.

3. Locally advanced or metastatic breast cancer that is not amenable to curative surgery and/or radiation (stage IIIB, IIIC, or IV).

4. Documentation of erbB-2 gene amplification by fluorescence in situ hybridization (FISH, as defined by a ratio >2.2) or chromogenic in situ hybridization (CISH, as defined by the manufacturer's kit instruction) or documentation of erbB-2 overexpression by immunohistochemistry (IHC, defined as IHC3+, or IHC2+ with FISH or CISH confirmation) based on local laboratory or initial diagnostic results utilizing one of the sponsor-approved assays. If erbB-2 status was determined using a test other than a sponsor-approved assay as defined in attachment 1, testing and study eligibility must be obtained from the sponsor-identified central laboratory prior to randomization.

5. All subjects must have tumor tissue available for central review of erbB-2 expression levels by FISH testing performed by the sponsor-identified central laboratory.

6. Disease progression on or following a prior trastuzumab-containing treatment regimen (regimen should have been given for a duration of at least 6 weeks), alone or in combination with cytotoxic chemotherapy, for metastatic or locally advanced disease. A 2 week washout period is required between trastuzumab treatment and first dose of the test article.

7. Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, and/or metastatic disease treatment settings.

8. At least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (specifically, ascites, pleural or pericardial effusion, osteoblastic bone metastases, and carcinomatous lymphangitis of the lung will not be considered measurable lesions). Subjects with skin lesions that are measurable by Computed Tomography (CT) scans or Magnetic Resonance Imaging (MRI) as the only site of measurable disease are allowed.

9. Eastern Cooperative Oncology Group (ECOG) status of 0,1 or 2 (not declining within 2 weeks prior to signing of informed consent).

10. Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by multiple-gated acquisition (MUGA) or echocardiogram (ECHO).

11. Screening lab values within the following parameters:
• Absolute neutrophil count (ANC): =1.5 × 109/L (1,500/mm3)
• Platelet count: =100 ×109/L (100,000/mm3)
• Hemoglobin: = 9.0 g/dL (90g/L)
• Serum creatinine: =1.5 × upper limit of normal (ULN)
• Total bilirubin: =1.5 × ULN (<3 ULN if Gilbert's disease)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): =2.5 × ULN (< 5 × ULN if liver metastases are present).

12. Recovery (to grade 1 or baseline) from all clinically significant adverse effects related to prior therapies (excluding alopecia).

13. All subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control starting 2 weeks prior to the administration of the first dose of test article until 28 days after the last dose of test article. A subject is biologically capable of having children if she is using contraceptives or if her sexual partner is sterile or using contraceptives.

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
Exclusion criteria:
1. More than 2 prior trastuzumab-based regimens for metastatic or locally advanced disease.

2. Subjects with prior exposure to capecitabine, lapatinib, or other erbB-2 targeted treatments (with the exception of trastuzumab).

3. Prior treatment with anthracyclines with a cumulative dose of doxorubicin of > 400 mg/m2 or epirubicin dose > 800 mg/m2, or the equivalent dose for other anthracycline derivatives.

4. Subjects with bone as the only site of disease.

5. Active uncontrolled or symtomatic CNS metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Subjects with a history of CNS metastases or spinal cord compression are allowable if they have been definitively treated and are off anticonvulsivants and steroids for at least 4 weeks before the first dose of test article.

6. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn disease, malabsorption, or grade =2 diarrhea of any etiology at baseline).

7. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association [NYHA] functional classification of =3), unstable angina, or myocardial infarction.

8. Family history of long or short QT syndrome, Brugada syndrome or subjects with QT/QTc interval > 0.45 second or known history of QT/QTc prolongation or torsade de pointes (TdP).

9. Renal insufficiency defined as creatinine clearance < 50 mL/min (as calculated by Cockroft and Gault Method, and normalized to body surface area).

10. History of known hypersensitivity to lapatinib, capecitabine, 5-fluorouracil, or any of their excipients, or known dihydropyrimidine dehydrogenase deficiency.

11. Major surgery, chemotherapy, radiotherapy, any investigational agents, or other cancer therapy within 2 weeks before administration of the first dose of test article.

12. Inability or unwillingness to swallow tablets or capsules.

13. Any other cancer within 5 years prior to screening with the exception of adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.

14. Pregnant, breast-feeding, or women of child bearing potential who are not using effective contraception during participation in the study and do not agree to do so for at least 28 days after final dose of study drug.

15. Evidence of significant medical illness or abnormal laboratory finding that would, in the investigator’s judgment, make the subject inappropriate for this study. Examples include, but are not limited to, serious active infection (ie, requiring intravenous antibiotic or antiviral agent) or uncontrolled major seizure.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Locally advanced or metastatic breast cancer
MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer

Intervention(s)

Product Name: neratinib
Product Code: HKI-272
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: neratinib
CAS Number: 698387-09-06
Current Sponsor code: WAY-179272-B
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: XELODA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
CAS Number: 154361-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: TYVERB
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: lapatinib
CAS Number: 231277-92-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: XELODA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
CAS Number: 154361-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: XELODA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
CAS Number: 154361-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: XELODA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
CAS Number: 154361-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Primary end point(s): The primary endpoint is the comparison of the independently assessed progression-free survival (PFS) following treatment with single agent neratinib versus lapatinib plus capecitabine in subjects with erbB-2-positive locally advanced or metastatic breast cancer. Progression-free survival is the time from the date of randomization to the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable tumor evaluation.

Secondary Objective: - to compare overall survival, objective response rate, duration of response, and clinical benefit rate (complete response+ partial response+ stable disease =24 weeks)
- to compare the frequency of and time to symptomatic or progressive central nervous system lesions in both treatment arms
- to compare safety
- to compare the frequency of grade 3 or higher diarrhea (as graded by CTCAE V3)
- to compare the frequency of palmar-plantar erythrodysesthesia (as graded by CTCAE V3)
- to assess population pharmacokinetics of neratinib
- to compare patient reported breast cancer specific quality of life between treatment arms
- to assess frequency of new or progressive central nervous system lesions and rate of symptomatic brain metastases

Main Objective: to compare the independently assessed progression-free survival (PFS) following treatment with single agent neratinib versus lapatinib plus capecitabine in subjects with erbB2 positive locally advanced or metastatic breast cancer.

Secondary ID(s)

3144A2-3003

2008-005425-11-HU

Ethics review

Status: Approved
Approval date: 28/12/2009
Contact:

Results

• Results available: Yes
• Date Posted: 25/12/2016
• Date Completed: 19/12/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-005425-11/results