Phase II Lapatinib Plus Nab-Paclitaxel As First And Second Line Therapy In her2+ MBC

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00709761
First received: July 1, 2008
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

This is an open-label, single-arm, multi-center, Phase II study to determine the activity of nab-paclitaxel plus lapatinib in the first and second-line setting in women with ErbB2 overexpressing metastatic breast cancer (MBC). Sixty subjects will be enrolled in the study. Subjects will receive nab-paclitaxel (100 mg/m2 intravenously once weekly for 3 weeks, followed by a rest week in a 4-week cycle) plus lapatinib (1000 mg once 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 nab-paclitaxel administered in women with ErbB2 overexpressing MBC who have received no chemotherapeutic regimen in the metastatic setting. 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 8 and 12 week intervals, and at the end of treatment.

Subject: Metastatic Breast Cancer, ErbB2, First-line therapy, Lapatinib, Nab-paclitaxel


Condition Intervention Phase
Neoplasms, Breast
Drug: Lapatinib/nab-Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: LPT 111111- A Single-arm, Multicenter Phase II Study to Evaluate The Combination of Weekly Nanoparticle Albumin Bound Paclitaxel (Nab-Paclitaxel or ABRAXANE®) and Lapatinib (TYKERB®) in Women With No More Than One Prior Treatment for ErbB2 Overexpressing Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Overall Tumor Response (OR) [ Time Frame: Start of treatment to disease progression or death or discontinuation from study or at least 28 days after last dose (up to Week 131) ] [ Designated as safety issue: No ]
    OR was defined as the percentage of participants experiencing either a confirmed complete response (CR) or a confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.0. CR is defined as the disappearance of all lesions (target and/or non-target). PR is defined as at least a 30% decrease in the sum of the longest dimensions (LD) of target lesions taking as a reference the baseline sum LD, with non-target lesions not increased or absent.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Start of treatment to death (up to Week 131) ] [ Designated as safety issue: No ]
    OS was defined as the time from the start of treatment until death due to any cause. For participants who did not die, time to death was censored at the time of last contact. OS could not be analyzed because only 13 participants had died as of data cut off, and data were not mature (greater than 75% of the participants were censored for the endpoint).

  • Duration of Response (DOR) [ Time Frame: First documented response (CR or PR) to disease progression or death (up to Week 131) ] [ Designated as safety issue: No ]
    DOR was defined for the subset of participants who showed a confirmed CR or PR, as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

  • Time to Response (TTR) [ Time Frame: Start of treatment to first documented response (CR or PR) (up to Week 131) ] [ Designated as safety issue: No ]
    TTR was defined for the subset of participants who showed a confirmed CR or PR, as the time from the start of treatment until the first documented evidence of CR or PR (whichever status was recorded first).

  • Time to Progression (TTP) [ Time Frame: Start of treatment to disease progression or death (up to Week 131) ] [ Designated as safety issue: No ]
    TTP was defined as the interval between the start of treatment until the earliest date of disease progression or death due to breast cancer.

  • Progression-Free Survival (PFS) [ Time Frame: Start of treatment to disease progression or death (up to Week 131) ] [ Designated as safety issue: No ]
    PFS was defined as the time from the start of treatment until the earliest date of disease progression or death due to any cause, if sooner.


Enrollment: 60
Study Start Date: July 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm
Single arm combination therapy of Lap and NabPaclitaxel combination
Drug: Lapatinib/nab-Paclitaxel
This is an open-label, single-arm, multi-center, Phase II study to determine the activity of nab-paclitaxel plus lapatinib (TYKERB) in the first and second-line setting in women with ErbB2 overexpressing metastatic breast cancer (MBC). Sixty subjects will be enrolled in the study. Subjects will receive nab-paclitaxel (100 mg/m2 intravenously on Day 1, 8, 15, every 28 days (q28) days plus lapatinib (1000 mg once daily on a continuous basis).
Other Name: Lapatinib/nab-Paclitaxel

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  • 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 FISH using a local laboratory result (which will be considered sufficient in this study with no further verification by a central laboratory).
  • Subjects must have received no more than one prior chemotherapeutic regimen in the metastatic setting.
  • If a taxane had been administered in the neoadjuvant, adjuvant or metastatic setting, progression must have occurred ≥12 months after completion of this treatment.
  • Prior therapy with radiation for this breast cancer population is permitted if it was administered in the neoadjuvant or adjuvant non metastatic setting. Radiotherapy given in the metastatic setting, prior to initiation of study medication, is allowed to a limited area (e.g., palliative therapy and involving less than 25% of bone marrow), if it is not the sole site of disease. Subjects must have completed radiation treatment and recovered from all acute radiation treatment related toxicities (e.g., bone marrow suppression) prior to commencement of combination treatment.
  • The subject must have received all prior chemotherapy treatment at least 4 weeks prior to enrollment in this study and must have recovered from all related toxicities. Subjects who have received weekly dose of prior chemotherapy e.g. gemcitabine or capecitabine may enroll 2 to 3 weeks after cessation of treatment provided that they have recovered from all related toxicities.
  • Prior therapy with trastuzumab in the neoadjuvant, adjuvant or metastatic setting is permitted. The subject must have received all prior trastuzumab treatment at least 4 weeks prior to enrollment in this study and must have recovered from all related toxicities.
  • Prior endocrine therapy is permitted in the neoadjuvant or adjuvant or metastatic setting. The subject must have received all prior endocrine treatment at least 1 week prior to enrollment in this study and must have recovered from all related toxicities.
  • Prior diagnosis of cancer is allowed as long as the subject is free of disease for 5 years. Subjects with completely resected basal or squamous cell skin cancer, thyroid cancer or successfully treated cervical carcinoma in-situ will be allowed if it has been 1 year or greater since definitive surgery.
  • Subjects must have measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter [LD] to be recorded) by mammogram, ultrasound or physical exam [Therasse, 2000].
  • Subjects with liver metastases or stable chronic liver disease are permitted into the study.
  • Women ≥18 years of age:
  • 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 1 of the following:
  • Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 5 days after the final dose of study medication; or
  • Consistent and correct use of 1 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 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.
  • Considered by the Investigator to have a life expectancy of ≥6 months.
  • ECOG Performance Status (PS) of 0 or 1 (Karnofsky ≥80%) [Oken, 1982].
  • Subjects must have normal organ and marrow function as defined in Table 3:

CONFIDENTIAL UM2007/00382/01 LPT111111 28

  • Table 3 Baseline Laboratory Values for Adequate Organ Function
  • Hematologic
  • Absolute neutrophil count ≥1.5 × 10^9/L
  • Hemoglobin ≥9 g/dL
  • Platelets ≥100 × 10^9/L
  • Hepatic
  • Serum bilirubin ≤ upper limit of normal (ULN)
  • Aspartate aminotransferase and alanine aminotransferase
  • ≤3 × ULN without liver metastases
  • ≤5 × ULN if documented liver metastases
  • Renal
  • Serum creatinine ≤1.5 mg/dL
  • OR -
  • Calculated creatinine clearance ≥40 mL/min
  • Subjects must have a cardiac ejection fraction of >50% as measured by echocardiogram (ECHO) or multigated acquisition scan (MUGA) and within the institutional range of normal.
  • Subjects with stable central nervous system metastases (stable for at least 3 months) as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI) or evidence of leptomeningeal involvement are eligible only if they are not taking steroids or enzyme-inducing anticonvulsants.
  • Subject must be free of gastrointestinal diseases that impede swallowing and retaining of oral medications.
  • Signed, informed consent prior to registration.
  • 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 whose disease is estrogen receptor + and/or progesterone receptor + or unknown status will only be included in the study if they meet the following criteria:
  • They have symptomatic visceral disease that requires chemotherapy.
  • Significant visceral organ tumor burden
  • The disease is considered by the Investigator to be progressing rapidly or is life threatening.
  • Subjects who have received prior endocrine therapy and who are no longer benefiting from this therapy.

Exclusion Criteria:

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

  • Subjects who have received more than one prior chemotherapeutic regimen in the metastatic setting
  • 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 (Section 5.11.2). This includes human immunodeficiency virus-positive subjects receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with lapatinib.
  • Prior treatment with lapatinib.
  • Concurrent anticancer or concomitant radiotherapy treatment;
  • Concurrent treatment with prohibited medications (Section 5.11.2);
  • 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 history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or nab-paclitaxel or 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.
  • 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)
  • 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.
  • 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, a requirement for iv alimentation, prior surgical procedures affecting absorption e.g. gastric resection and uncontrolled inflammatory bowel disease (e.g., Crohn's, ulcerative colitis).
  • Peripheral neuropathy of Grade 2 or greater.
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
  • History of prior malignancy. However, subjects who have been disease-free for 5 years, or subjects with completely resected basal or squamous cell skin cancer, thyroid cancer or successfully treated cervical carcinoma in situ will be eligible if it has been at least 1 year since definitive surgery.
  • or rendering of informed consent.

Other Eligibility Criteria Considerations:

  • To assess any potential impact on subject eligibility with regard to safety, the Investigator must refer to the following document(s) for detailed information regarding warnings, precautions, contraindications, AEs, and other significant data pertaining to the investigational product(s) being used in this study: Clinical Investigator's Brochure (IB), SPM, and the nab-paclitaxel Product Label.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00709761

Locations
United States, California
GSK Investigational Site
La Verne, California, United States, 91750
GSK Investigational Site
Long Beach, California, United States, 90813
United States, Florida
GSK Investigational Site
Fort Myers, Florida, United States, 33916
GSK Investigational Site
Jupiter, Florida, United States, 33458
GSK Investigational Site
St Petersburg, Florida, United States, 33705
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30341
United States, Kentucky
GSK Investigational Site
Paducah, Kentucky, United States, 42003
United States, New York
GSK Investigational Site
New York, New York, United States, 10065
GSK Investigational Site
Rochester, New York, United States, 14623
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45242
GSK Investigational Site
Cleveland, Ohio, United States, 44106
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97213
United States, Rhode Island
GSK Investigational Site
Woonsocket, Rhode Island, United States, 02895
United States, Tennessee
GSK Investigational Site
Chattanooga, Tennessee, United States, 37404
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Lubbock, Texas, United States, 79410
United States, Virginia
GSK Investigational Site
Danville, Virginia, United States, 24541
GSK Investigational Site
Richmond, Virginia, United States, 23230
GSK Investigational Site
Salem, Virginia, United States, 24153
United States, Washington
GSK Investigational Site
Everett, Washington, United States, 98201
GSK Investigational Site
Seattle, Washington, United States, 98101
GSK Investigational Site
Spokane, Washington, United States, 99218
GSK Investigational Site
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00709761     History of Changes
Other Study ID Numbers: LPT111111
Study First Received: July 1, 2008
Results First Received: October 13, 2011
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Erbb2
ABRAXANE
MBC
first or second line therapy
Metastatic Breast Cancer
TYKERB

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Lapatinib
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 21, 2014