Clinical trial NCT00479856: Lapatinib In Combination With Chemotherapy In Subjects With Relapsed Breast Cancer
Official title: An Open-label, Multi-centre Study of Lapatinib in Combinationwith Chemotherapy in Patients With ErbB2 Overexpressing Breastcancer After Trastuzumab Failure in the Neoadjuvant or Adjuvantsetting.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Relapsed Breast Cancer
Neoplasms, Breast
Keywords: ErbB1
ErbB2
GW572016
lapatinib
Relapsed breast cancer
dual tyrosine kinase inhibitor
MBC
EGFR
Her-2/neu
FISH amplification
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-05-28
Enrollment: 9
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and efficacy of lapatinib in combination with chemotherapy (capecitabine, docetaxel, nab-paclitaxel) in subjects with ErbB2-overexpressing breast cancer whose disease has progressed during or within 12 months after completion of trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent.
* Histologically/cytologically confirmed breast cancer;

If the disease is restricted to a solitary lesion, the neoplastic nature of the lesion must be confirmed by cytology or histology.

* Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors) \[Therasse, 2000\].
* Documented amplification of the ErbB2 gene by fluorescence in situ hybridization (FISH) or documented overexpression of the ErbB2 protein by 3+ IHC in primary or metastatic tumor tissue.
* Subjects must have relapsed breast cancer where the disease progressed during or ≤ 12 months after completion of trastuzumab-containing therapy in the neoadjuvant or adjuvant setting.

Note: Progression is defined using RECIST criteria, that is, either the appearance of new lesions or a \>=20% increase in the sum of longest diameter (LD).

* Subjects must not have received prior anti-cancer therapy for metastatic breast cancer (MBC). Subjects who received prior antihormonal agents combined with trastuzumab for the treatment of disease which first presented as ER positive MBC and recurred while receiving trastuzumab or ≤ 3 months after completing this therapy are eligible.
* Subjects with stable central nervous system (CNS) metastases as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI) are allowed. Treatment with prophylactic anticonvulsants is permitted, unless listed within the Prohibited Medications.
* Subjects must have a baseline cardiac ejection fraction (LVEF) ³50% measured by echocardiogram (ECHO) (or multigated acquisition (MUGA) scan if an ECHO cannot be performed). The same modality used at baseline must be used for repeat assessment throughout study. Only subjects with controlled or asymptomatic angina or arrhythmias are eligible.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.
* Subjects must have archived tumor tissue from the initial diagnosis available for analysis. If tissue from the initial diagnosis is not available, then tissue must be obtained from a recurrent or metastatic site prior to initiating study treatment.
* Female ≥18 years.
* Subject must have adequate organ function as defined in Table 1.
* Table 1: Baseline Laboratory Values for Adequate Organ Function.

SYSTEM

Hematologic:

Absolute neutrophil count: ≥1.5 X 10\^9/L

Hemoglobin: ≥9 g/dL

Platelets: ≥ 75 X 10\^9/L

Hepatic:

AST, ALT and Alkaline phosphatase: ≤ 2.5 X ULN

Unless concomitant docetaxel, then ≤ 1.5 x ULN for AST and ALT, with AP ≤ 2.5 x ULN

Unless documented liver metastasis, then ≤ 5 x ULN

Serum bilirubin: ≤ 2.0 X ULN

Albumin: ≥ 2.5 g/dL

Renal:

Serum Creatinine: ≤ 1.5 mg/dL

* OR - Calculate Creatinine Clearance: ≥ 40 mL/min

  1. Calculated by the Cockcroft and Gault Method \[Cockcroft , 1976\].

Exclusion Criteria:

* Pregnant or lactating females.
* Women of childbearing potential who do not practice approved contraceptive methods (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.
* History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
* Concurrent therapy given to treat cancer (chemotherapy, radiation therapy, immunotherapy, biologic therapy, anti-hormonal therapy) while taking study medication.
* Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
* Malabsorption syndrome or resection of the stomach or small bowel significantly affecting gastrointestinal function.
* Have current active haptic or biliary disease (with excpetion of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
* Concurrent disease or condition that, in the opinion of the physician, would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety (for example, uncontrolled infection, or any psychiatric condition prohibiting understanding or rendering of informed consent).
* Concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents for anti-cancer therapy.
* Bisphosphonates may not be initiated after the first dose of study medication.
* Considered by the Investigator to have a life expectancy less than 3 months.
* Not able to swallow or retain oral medication.
* The subject with a known unmanageable hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients and those related to capecitabine, docetaxel, nab paclitaxel or their excipients.

Primary outcomes:
measure: Overall Tumor Response
timeFrame: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 wks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, of other reason)
Secondary outcomes:
measure: Clinical Benefit (CB)
timeFrame: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason)
measure: Duration of Response
timeFrame: time from first documented evidence of CR or PR until the first documented sign of disease progression or death (approximately 95 weeks)
measure: Time to Response (TTR)
timeFrame: start of treatment until first documented evidence of CR or PR (approximately 95 weeks)
measure: Progression-free Survival
timeFrame: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 weeks); dependent on when participant discontinued study therapy due to disease progression, death, adverse event, or other reason)
measure: Number of Participants With the Indicated Serious Adverse Events and Adverse Events
timeFrame: Baseline through End of Treatment, or discontinuation of study therapy (approximately 95 weeks); from the first dose of lapatinib until 5 days after the last dose of lapatinib
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Burbank
country: United States
facility: GSK Investigational Site
state: California
city: Highland
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Hollywood
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Lawrenceville
country: United States
facility: GSK Investigational Site
state: Georgia
city: Zion
country: United States
facility: GSK Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Tupelo
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Voorhees
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Sumter
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Ogden
country: United States
facility: GSK Investigational Site
state: Utah
city: Abingdon
country: United States
facility: GSK Investigational Site
state: Virginia
city: Fairfax
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: