Lapatinib Combined With Paclitaxel For Patients With First-Line ErbB2-Amplified Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00356811
First received: July 25, 2006
Last updated: January 9, 2014
Last verified: January 2014

July 25, 2006
January 9, 2014
May 2006
March 2008   (final data collection date for primary outcome measure)
Overall tumor response rate. [ Time Frame: Tumor measurement assessments are conducted every 8 weeks. ] [ Designated as safety issue: No ]
Overall Response Rate is defined as percentage of patients achieving either a confirmed complete or partial response as determined by an independent review committee (IRC).
Overall tumor response rate.
Complete list of historical versions of study NCT00356811 on ClinicalTrials.gov Archive Site
Overall survival, Duration of response, Time to response, Time to progression, Progression-free survival, Determine toxicities associated with the study treatments. [ Time Frame: Safety assessments are conducted every 4 weeks. Efficacy assessments are conducted every 8 weeks. Survival follow-up visits are conducted every 12 weeks after protocol treatment discontinuation. ] [ Designated as safety issue: No ]
Overall survival Duration of response Time to response Time to progression Progression-free survival Determine toxicities associated with the study treatments.
Not Provided
Not Provided
 
Lapatinib Combined With Paclitaxel For Patients With First-Line ErbB2-Amplified Metastatic Breast Cancer
An Open-label, Single-arm, Multi-centre, Phase II Study of Oral Lapatinib in Combination With Paclitaxel as First-line Treatment for ErbB2-amplified Metastatic Breast Cancer Patients

This study investigates the safety and efficacy of oral lapatinib in combination with an approved medication, paclitaxel, for patients with ErbB2 metastatic breast cancer.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Neoplasms, Breast
  • Drug: Lapatinib oral tablets
    Lapatinib will be given as tablets contain 410 mg of lapatinib ditosylate monohydrate, equivalent to 250 mg lapatinib free base per tablet. Subjects will be given a 4 week supply of lapatinib tables and instructed to take 6 tablets daily (1500 mg daily dose) orally at the same time each day. Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent.
    Other Name: Tykerb/ Tyverb
  • Drug: Paclitaxel infusion
    Subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle). Subjects will be treated with paclitaxel for at least 6 months, and may continue on paclitaxel at the discretion of the Investigator, or discontinued sooner if the subject has disease progression, an unacceptable toxicity or withdraws consent.
    Other Name: Taxol
Experimental: Single arm
Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Subjects will be treated with paclitaxel for at least 6 months, and may continue on paclitaxel at the discretion of the Investigator, or discontinued sooner if the subject has disease progression, an unacceptable toxicity or withdraws consent.
Interventions:
  • Drug: Lapatinib oral tablets
  • Drug: Paclitaxel infusion

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
53
December 2013
March 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

  • Signed informed consent.
  • Only females ≥18 years of age will be recruited:

    • Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal); or
    • 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 oligomenorrhoea (severe), women who are perimenopausal and young women who have begun to menstruate. These subjects must provide 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.
    • Implants of levonorgestrel.
    • Injectable progestogen.
    • Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
    • Oral contraceptives (either combined or progestogen only).
    • Barrier methods, including diaphragm or condom with a spermicide.
  • Subjects must have histologically confirmed invasive breast cancer with stage IVdisease;

    • Where the disease is restricted to a solitary lesion, the neoplastic nature of the lesion should be confirmed by cytology or histology.

  • Subjects whose disease is ER+ and/or PR+ or unknown status will only be included in the study if they meet the following criteria:

    • They have symptomatic visceral disease that requires chemotherapy (e.g., patients with liver or lung metastases).
    • The disease is considered by the Investigator to be progressing rapidly or lifethreatening.
    • Subjects who have received endocrine therapy and who are no longer benefiting from this therapy.
  • Documented amplification of ErbB2 defined by FISH in primary or metastatic tumor tissue. Results of FISH testing at local laboratories are acceptable, however, tissue sample must still be sent to Central laboratory where results will be repeated but not used for eligibility criterion.
  • If a taxane had been administered in the neoadjuvant or adjuvant setting, progression must have occurred ≥12 months after completion of this treatment.
  • Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria [Stephens, 2004; Therasse, 2000].
  • Radiotherapy prior to initiation of study medication is allowed to a limited area (e.g., palliative treatment for painful bone metastases), if it is not the sole site of disease. Subject must have completed radiation treatment and recovered from all acute radiation treatment-related toxicities, in particular bone marrow suppression.
  • Bisphosphonate therapy for bone metastases is allowed however; treatment must be initiated prior to the first dose of study medication. Prophylactic use of bisphosphonates in subjects without bone disease, except for the treatment of osteoporosis, is not permitted.
  • Subjects with stable central nervous system (CNS) metastases (stable for at least 3 months) as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI)) or leptomeningeal involvement are eligible only if they are not taking oral steroids or enzyme-inducing anticonvulsants.
  • Subjects must have a cardiac ejection fraction within institutional range of normal as measured by echocardiogram (or multigated acquisition (MUGA) scan if an echocardiogram cannot be performed or is inconclusive). Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are not eligible.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 1.
  • Considered by the Investigator to have a life expectancy of at least 3 months.
  • Able to swallow and retain oral medication.
  • Subjects must have new or archived tumor tissue available for analysis.
  • Subjects must complete all screening assessments as outlined in the protocol.
  • Subject must have adequate organ function as defined in Table 1.

Table 1 Baseline Laboratory Values for Adequate Organ Function SYSTEM LABORATORY VALUES

Haematologic

Absolute neutrophil count ≥1.5 × 10^9/L Haemoglobin ≥9 g/dL Platelets ≥100 × 10^9/L

Hepatic

Albumin ≥2.5 g/dL Serum bilirubin

  • 1.25 x ULN AST and ALT ≤3 × ULN without liver metastases
  • 5 × ULN with documented liver metastases

Renal

Serum Creatinine1 ≤2.0 mg/dL

  • OR - Calculate Creatinine Clearance1 ≥40 mL/min

    1. Calculated by the Cockcroft and Gault Method. ALT = alanine aminotransferase; AST = aspartate aminotransferase

      Exclusion Criteria:

      A subject will not be eligible for inclusion in this study if any of the following criteria apply:

  • Pregnant or lactating females.
  • Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy for metastatic disease.
  • Prior therapy with ErbB1 and/or ErbB2 inhibitors.
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy) while taking study medication.
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
  • Peripheral neuropathy of grade 2 or greater.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded.
  • 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 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.
  • Active or uncontrolled infection.
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.
  • Concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents.
  • Used an investigational drug within 30 days or five half-lives, whichever is longer, preceding the first dose of investigational treatment.
  • The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients and those related to paclitaxel or excipients.
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Latvia,   Poland,   Romania,   Russian Federation
 
NCT00356811
EGF105764
No
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP