Lapatinib + Vinorelbine in ErbB2 Overexpressing, First or Second Line Metastatic Breast Cancer Subjects

NCT00709618 | Terminated Phase 2 Results

• 1 other identifier: LPT111110
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 22

Brief Summary

This is an open-label, single-arm, multi-center, Phase II study to determine the activity of vinorelbine plus lapatinib in either first- or second-line setting in women with ErbB2 overexpressing metastatic breast cancer (MBC). Sixty subjects will be enrolled in the study. Subjects will receive vinorelbine intravenously once weekly for 3 weeks, followed by a rest week in a 4-week cycle) plus lapatinib daily. Subjects will receive treatment until disease progression or withdrawal from the study. The primary objective of this study is to evaluate overall tumor response rate of lapatinib in combination with vinorelbine. Secondary objectives include progression-free survival, overall survival, duration of response, time to response and time to progression and safety. Safety and efficacy assessments will be performed at 4, 8 and 12 week intervals, and at the end of treatment. Subject: Metastatic Breast Cancer, ErbB2, First-line or Second-line therapy, Lapatinib, Vinorelbine

Conditions

Neoplasms, Breast

Keywords

Erbb2; MBC; First or Second line therapy; Metastatic Breast Cancer; Vinorelbine; Tykerb

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Overall Response (OR), as Assessed by the Investigator

  OR is defined as the number of participants achieving either a confirmed complete response (CR: the disappearance of all target lesions \[TLs\]) or partial response (PR: a \>=30% decrease in the sum of the longest diameter \[LD\] of the TLs, taking as a reference the baseline sum LD) as assessed by the investigator as the best OR. The best OR is the best response recorded from the start of treatment until disease progression (PD: a \>=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since treatment started or the appearance of \>=1 new lesions)/recurrence.

  From the start of study medication until disease progression, assessed every 8 weeks for up to 2 years

Secondary Outcomes (6)

• Progression-Free Survival (PFS), as Assessed by the Investigator

  From the start of study medication until disease progression, assessed every 8 weeks for up to 2 years

• Duration of Response, as Assessed by the Investigator

  From the start of study medication until disease progression, assessed every 8 weeks for up to 2 years

• Time to Response, as Assessed by the Investigator

  From the start of study medication until disease progression, assessed every 8 weeks for up to 2 years

• Time to Progression (TTP), as Assessed by the Investigator

  From the start of study medication until disease progression, assessed every 8 weeks for up to 2 years

• Number of Participants With the Indicated Adverse Events Occurring in at Least 5 Participants and Related to the Combination of Lapatinib and Vinorelbine

  From the start of study medication until disease progression, assessed every 4 weeks for up to 2 years

Interventions

Lapatinib, Vinorelbine DRUG

Vinorelbine intravenously once weekly for 3 weeks, followed by a rest week in a 4-week cycle) plus lapatinib daily

Also known as: Lapatinib, Vinorelbine

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 prior to registration.
• Considered by the Investigator to have a life expectancy of ≥12 weeks.
• Subjects must 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.
• Documented amplification of ErbB2 3+ by immunohistochemistry or a positive score (\>2.2) by fluorescence in situ hybridization (FISH) using a local laboratory result (which will be considered sufficient in this study with no further verification by a central laboratory). NOTE: If both IHC and FISH results available, FISH results must be used for eligibility.
• Subjects must not have received more than 1 prior chemotherapeutic regimen in the metastatic setting.
• All prior chemotherapy, immunotherapy, biologic therapy, or surgery (except for minor surgical procedures) must be discontinued at least 4 weeks prior to first dose of investigational product. Hormonal therapy must be discontinued at least 1 week prior to first dose.
• Prior diagnosis of cancer is allowed as long as the subject is free of disease and has been off treatment for prior malignancies for 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 surgery.
• Subjects must have measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
• 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 with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progestogen only) where not contraindicated for this subject population or per local practice.; or barrier methods, including diaphragm or condom with a spermicide.
• ECOG performance status (PS) of 0 to 2 \[Oken, 1982\] (Appendix 1).

You may not qualify if:

• Subjects taking treatment with medications provided in the list of restricted medications and substances in the drug information section for lapatinib 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.
• Prior therapy with lapatinib.
• Prior therapy with vinorelbine for treatment of breast cancer.
• More than 1 line of therapy for treatment of MBC.
• Concurrent anticancer or concomitant radiotherapy treatment.
• 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.
• 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)
• 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.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the agents used in this study or their excipients.
• 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.
• Concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety.
• Pregnant or lactating females at any time during the study (due to the potential teratogenic or abortifacient effects of lapatinib and breastfeeding).
• 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 or small bowel.
• Women with ulcerative colitis are also excluded.
• Peripheral neuropathy of Grade 2 or greater.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (22)

GSK Investigational Site

Muscle Shoals, Alabama, 35661, United States

Location

GSK Investigational Site

Tucson, Arizona, 85715, United States

Location

GSK Investigational Site

Sacramento, California, 95817, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32204, United States

Location

GSK Investigational Site

Plantation, Florida, 33324, United States

Location

GSK Investigational Site

Augusta, Georgia, 30901, United States

Location

GSK Investigational Site

Cedar Rapids, Iowa, 52402, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21237, United States

Location

GSK Investigational Site

Bethesda, Maryland, 20817, United States

Location

GSK Investigational Site

Jackson, Mississippi, 39202, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64118, United States

Location

GSK Investigational Site

St Louis, Missouri, 63141, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68114, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Greensboro, North Carolina, 27403, United States

Location

GSK Investigational Site

Columbus, Ohio, 43219, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73120, United States

Location

GSK Investigational Site

Tulsa, Oklahoma, 74136, United States

Location

GSK Investigational Site

Eugene, Oregon, 97401, United States

Location

GSK Investigational Site

Portland, Oregon, 97239-3098, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19106, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38120, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Vinorelbine

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; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Limitations and Caveats

The study was terminated due to low screening and a low enrollment rate after 3 years.

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2008
• First Posted: July 3, 2008
• Study Start: June 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: July 14, 2014
• Results First Posted: January 18, 2013

Record last verified: 2014-06

Locations

US (22)