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

NCT00356811 | Completed Phase 2 Results

• 1 other identifier: EGF105764
• Study Type: interventional
• Target: 57
• Locations: 4 countries
• Sites: 13

Brief Summary

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

Conditions

Neoplasms, Breast

Keywords

Lapatinib; Metastatic breast cancer; Paclitaxel; ErbB2-amplification; GW572016

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC)

  OR is defined as the number of participants achieving either a CR or PR, per Response Evaulation Criteria in Solid Tumors (RECIST). The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made \>=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.

  From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)

Secondary Outcomes (9)

• Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator

  From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)

• Duration of Response (DoR), as Assessed by the IRC

  From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)

• Duration of Response (DoR), as Assessed by the Investigator

  From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)

• Time to Response, as Assessed by the IRC

  From randomization until the first documented evidence of a PR or CR (up to Week 86)

• Time to Response, as Assessed by the Investigator

  From randomization until the first documented evidence of a PR or CR (up to Week 86)

Study Arms (1)

Single arm

EXPERIMENTAL

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.

Drug: Lapatinib oral tablets; Drug: Paclitaxel infusion

Interventions

Lapatinib oral tablets DRUG

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.

Also known as: Tykerb/ Tyverb

Single arm

Paclitaxel infusion DRUG

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.

Also known as: Taxol

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (13)

GSK Investigational Site

Liepāja, LV3401, Latvia

Location

GSK Investigational Site

Riga, LV 1002, Latvia

Location

GSK Investigational Site

Riga, LV 1079, Latvia

Location

GSK Investigational Site

Krakow, 31-115, Poland

Location

GSK Investigational Site

Olsztyn, 10-228, Poland

Location

GSK Investigational Site

Olsztyn, 10-699, Poland

Location

GSK Investigational Site

Warsaw, 02-781, Poland

Location

GSK Investigational Site

Bucharest, 022328, Romania

Location

GSK Investigational Site

Moscow, 115 478, Russia

Location

GSK Investigational Site

Moscow, 117997, Russia

Location

GSK Investigational Site

Moscow, 129 128, Russia

Location

GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

GSK Investigational Site

Saint Petersburg, 197758, Russia

Location

Related Publications (2)

• Jagiello-Gruszfeld A, Tjulandin Sergei S, Dobrovolskaya N et al, Lapatinib (L) with weekly paclitaxel (P) as first-line therapy for patients (pts) with HER2+ metastatic breast cancer (MBC). The 31st Annual San Antonio Breast Cancer Symposium; San Antonio TX: December 10-14 2008. Abstract 3145.

  BACKGROUND

• Jagiello-Gruszfeld A, Tjulandin S, Dobrovolskaya N, Manikhas A, Pienkowski T, DeSilvio M, Ridderheim M, Abbey R. A single-arm phase II trial of first-line paclitaxel in combination with lapatinib in HER2-overexpressing metastatic breast cancer. Oncology. 2010;79(1-2):129-35. doi: 10.1159/000318043. Epub 2010 Nov 22.

  PMID: 21088439 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2006
• First Posted: July 26, 2006
• Study Start: May 1, 2006
• Primary Completion: March 1, 2008
• Study Completion: December 1, 2013
• Last Updated: July 21, 2014
• Results First Posted: July 21, 2014

Record last verified: 2014-05

Locations

RO (1); RU (5); PL (4); LA (3)