Docetaxel, Carboplatin, and Trastuzumab and/or Lapatinib in Treating Women With Stage I, Stage II, or Stage III Breast Cancer That Can Be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of California, Los Angeles
Information provided by (Responsible Party):
Translational Oncology Research International
ClinicalTrials.gov Identifier:
NCT00769470
First received: October 8, 2008
Last updated: August 22, 2013
Last verified: August 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether docetaxel and carboplatin are more effective when given together with trastuzumab and/or lapatinib in treating women with stage I, stage II, or stage III breast cancer.

PURPOSE: This randomized phase II trial is studying how well docetaxel and carboplatin work when given together with trastuzumab and/or lapatinib in treating women with stage I, stage II, or stage III breast cancer that can be removed by surgery.


Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: carboplatin
Drug: docetaxel
Drug: lapatinib ditosylate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open Label, Randomized Phase II Trial of Presurgical Treatment With Single-Agent Trastuzumab (H) or Lapatinib (Ty) or the Combination of Trastuzumab and Lapatinib (H+Ty), Followed by Six Cycles of Docetaxel (T) and Carboplatin (C) With Trastuzumab (TCH) or Lapatinib (TCTy) or the Combination of Trastuzumab and Lapatinib (TCHTy) in Patients With HER2/Neu-Amplified Operable Breast Cancer

Resource links provided by NLM:


Further study details as provided by Translational Oncology Research International:

Primary Outcome Measures:
  • Pathologic complete response (pCR) [ Time Frame: 7 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of pCR rates [ Time Frame: 7 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: April 2009
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive trastuzumab IV over 90 minutes on day in course 1. Patients receive docetaxel IV, carboplatin IV, and trastuzumab IV over 30 minutes on day 1 in course 2-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: trastuzumab
Given IV
Drug: carboplatin
Given IV
Drug: docetaxel
Given IV
Experimental: Arm II
Patients receive oral lapatinib ditosylate once daily on days 1-21 in course 1. Patients receive docetaxel IV and carboplatin IV on day 1 and oral lapatinib ditosylate once daily on days 1-21 in courses 2-7.Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: carboplatin
Given IV
Drug: docetaxel
Given IV
Drug: lapatinib ditosylate
Given orally
Experimental: Arm III
Patients receive trastuzumab IV over 90 minutes on day 1 and oral lapatinib ditosylate daily on days 1-21. Starting on day 22, patients receive docetaxel IV, carboplatin IV, and trastuzumab IV three times a week and oral lapatinib ditosylate once daily on days 1-21 in courses 2-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: trastuzumab
Given IV
Drug: carboplatin
Given IV
Drug: docetaxel
Given IV
Drug: lapatinib ditosylate
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • To investigate the clinical efficacy of neoadjuvant docetaxel and carboplatin in combination with trastuzumab (Herceptin®) and/or lapatinib ditosylate by estimating the pathologic complete response (pCR) rate in the breast and axilla of women with HER2/neu-positive resectable stage I-III adenocarcinoma of the breast.

Secondary

  • To estimate the molecular effects of lapatinib ditosylate and trastuzumab alone or in combination on tumor tissues of these patients by assessing changes in gene expression using serial gene microarray analysis.
  • To assess for gene expression and/or biomarker changes that may be correlated with or predict pCR and clinical response to lapatinib ditosylate and/or trastuzumab in these patients.
  • To evaluate the safety and tolerability of these regimens in these patients.
  • To evaluate the clinical efficacy of these regimens by estimating the clinical objective response rate (complete response and partial response) in these patients.
  • To estimate the rate of congestive heart failure or drop in LVEF (> 10% points from baseline and below lower limits of normal) in each of the three treatment arms.

OUTLINE: This is a multicenter study. Patients are stratified according to baseline tumor size (≤ 3 cm vs > 3 cm) and hormone receptor status (estrogen receptor [ER]- and/or progesterone receptor [PR]-positive vs ER- and PR- negative). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive a trastuzumab IV over 90 minutes on day 1 in course 1. Patients receive docetaxel IV, carboplatin IV, and trastuzumab IV over 30 minutes on day 1 in courses 2-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral lapatinib ditosylate once daily on days 1-21 in course 1. Patients receive docetaxel IV, carboplatin IV as in arm I and oral lapatinib ditosylate once daily on days 1-21 in courses 2-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Arm III: Patients receive trastuzumab IV as in arm I on day 1 and oral lapatinib ditosylate as in arm II on days 1-21 in course 1. Patients receive docetaxel IV, carboplatin IV, and trastuzumab IV as in arm I on day 1 and oral lapatinib ditosylate as in arm II on days 1-21 in courses 2-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Within 4-6 weeks after completion of chemotherapy, all patients under go definitive surgery and/or radiotherapy at the discretion of the treating physician. Tumor biopsy and blood samples are collected for biomarker analysis and molecular analysis at baseline, after course 1, and at the time of definitive breast surgery or completion of chemotherapy. Gene expression changes are analyzed by mRNA microarray analysis and molecular changes in protein expression profiles by IHC. Samples may also be analyzed by RT-PCR.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women aged 18 to 70 years, inclusive
  • Histologically or cytologically confirmed adenocarcinoma of the breast
  • Stage I, II or III disease (early stage) with tumor measuring ≥ 1 cm and meeting any the following criteria:

    • Grade > 1
    • Estrogen receptor- and progesterone receptor-negative
    • Age ≤ 35 years
  • HER2/neu-positivity by fluorescence in situ hybridization (FISH)
  • Estrogen and progesterone receptor status known prior to study entry.
  • ECOG performance status 0-1 Adequate organ function (ejection fraction>- lower limit of normal) as determined by MUGA or echocardiogram.
  • If female of childbearing potential, pregnancy test is negative and is willing to use effective contraception while on treatment and for at least 3 months after the last dose of study therapy.
  • patient is accessible and willing to comply with treatment, tissue acquisition and follow up.
  • patient is willing to provide written informed consent prior to performance of any study-related procedure.
  • Adequate organ function as defined by the following laboratory values
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9.0 g/dL
  • Creatinine < 1.5 mg/dL
  • Total bilirubin ≤ 1.0 times upper limit of normal (ULN) (< 3 times ULN in patients with Gilbert's syndrome confirmed by genotyping or Invader UGTIA1 molecular assay)
  • Alkaline phosphatase (AP), ALT, and AST must meet 1 of the following criteria:
  • AP normal AND AST/ALT ≤ 2.5 times upper limit of normal (ULN)
  • AP ≤ 2.5 times ULN AND ALT/AST ≤ 1.5 times ULN
  • AP ≤ 5 times ULN AND AST/ALT normal

Exclusion Criteria:

  • Inflammatory breast cancer, defined as the presence of erythema or induration involving > 1/3 of the breast
  • Bilateral invasive breast cancer
  • Metastatic disease
  • Concurrent therapy with any other non-protocol anti-cancer therapy
  • history of any other malignancy within the past 5 years, with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix
  • pre-existing motor or sensory neurotoxicity ≥ grade 2 by NCI NTCAE version 3.0
  • cardiac disease including any of the following:
  • Myocardial infarction within the past 6 months
  • Unstable angina
  • New York Heart Association class II-IV congestive heart failure
  • inflammatory bowel disease or other bowel condition causing chronic diarrhea and requiring active therapy
  • active, uncontrolled infection requiring parenteral antimicrobials
  • known hypersensitivity to Chinese hamster ovary products or other recombinant human or humanized antibodies and/or known hypersensitivity to any of the study drugs or their ingredients (e.g., polysorbate 80 in docetaxel)
  • other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of study drugs or place the subject at undue risk for treatment complications
  • hormonal agent (e.g., raloxifene, tamoxifen citrate, or other selective estrogen receptor modulators) for osteoporosis or prevention of breast cancer. subjects must have discontinued these agents 14 days prior to first baseline biopsy.
  • prior ipsilateral radiotherapy for invasive or noninvasive breast cancer or to the ipsilateral chest wall for any malignancy
  • prior chemotherapy, radiotherapy, or endocrine therapy for currently diagnosed invasive or noninvasive breast cancer
  • concurrent ovarian hormonal replacement therapy. Prior treatment must be stopped prior to first baseline biopsy.
  • male subjects
  • pregnant or lactating subjects
  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: NCT00769470

Locations
United States, California
Central Hematology Oncology Medical Group, Incorporated - Alhambra
Alhambra, California, United States, 91801
Comprehensive Blood and Cancer Center
Bakersfield, California, United States, 93309-0633
St. Jude Heritage Medical Group at Virginia K. Crosson Cancer Center
Fullerton, California, United States, 92835
North Valley Hematology-Oncology Medical Group
Northridge, California, United States, 91328
Wilshire Oncology Medical Group, Incorporated - Pomona
Pomona, California, United States, 91767-3021
Sansum Medical Clinic
Santa Barbara, California, United States, 93105
Central Coast Medical Oncology Corporation
Santa Maria, California, United States, 93454
Santa Barbara Hematology Oncology - Solvang
Solvang, California, United States, 93463
Cancer Care Associates Medical Group, Incorporated - Redondo Beach
Torrance, California, United States, 90505
United States, Florida
Cancer Institute of Florida, PA - Orlando
Orlando, Florida, United States, 32804
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
Hematology and Oncology Consultants, PA - Orlando
Orlando, Florida, United States, 32804
United States, Indiana
Providence Medical Group
Haute Terre, Indiana, United States, 47802
United States, Nevada
Comprehensive Cancer Centers of Nevada - Henderson
Henderson, Nevada, United States, 89052
United States, New Mexico
New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87109
Sponsors and Collaborators
Translational Oncology Research International
University of California, Los Angeles
Investigators
Principal Investigator: Sara Hurvitz, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Translational Oncology Research International
ClinicalTrials.gov Identifier: NCT00769470     History of Changes
Other Study ID Numbers: CDR0000616008, P30CA016042, TRIO-TORI-B-07, SANOFI-AVENTIS-TRIO-TORI-B-07, WIRB-20080822
Study First Received: October 8, 2008
Last Updated: August 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Translational Oncology Research International:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
HER2-positive breast cancer

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

ClinicalTrials.gov processed this record on August 28, 2014