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

NCT ID: NCT00769470

Last Updated: 2016-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30

Brief Summary

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.

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

trastuzumab

Intervention Type: BIOLOGICAL

Given IV

carboplatin

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

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.

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

lapatinib ditosylate

Intervention Type: DRUG

Given orally

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.

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: BIOLOGICAL

Given IV

carboplatin

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

lapatinib ditosylate

Intervention Type: DRUG

Given orally

Interventions

trastuzumab

Given IV

Intervention Type: BIOLOGICAL

carboplatin

Given IV

Intervention Type: DRUG

docetaxel

Given IV

Intervention Type: DRUG

lapatinib ditosylate

Given orally

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

Translational Oncology Research International

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sara Hurvitz, MD

Role: PRINCIPAL_INVESTIGATOR

Jonsson Comprehensive Cancer Center

Locations

Central Hematology Oncology Medical Group, Incorporated - Alhambra

Alhambra, California, United States

Comprehensive Blood and Cancer Center

Bakersfield, California, United States

St. Jude Heritage Medical Group at Virginia K. Crosson Cancer Center

Fullerton, California, United States

North Valley Hematology-Oncology Medical Group

Northridge, California, United States

Wilshire Oncology Medical Group, Incorporated - Pomona

Pomona, California, United States

Sansum Medical Clinic

Santa Barbara, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

Santa Barbara Hematology Oncology - Solvang

Solvang, California, United States

Cancer Care Associates Medical Group, Incorporated - Redondo Beach

Torrance, California, United States

Cancer Institute of Florida, PA - Orlando

Orlando, Florida, United States

Florida Hospital Cancer Institute

Orlando, Florida, United States

Hematology and Oncology Consultants, PA - Orlando

Orlando, Florida, United States

Providence Medical Group

Haute Terre, Indiana, United States

Comprehensive Cancer Centers of Nevada - Henderson

Henderson, Nevada, United States

New Mexico Cancer Center

Albuquerque, New Mexico, United States

Countries

United States

References

Hurvitz SA, Caswell-Jin JL, McNamara KL, Zoeller JJ, Bean GR, Dichmann R, Perez A, Patel R, Zehngebot L, Allen H, Bosserman L, DiCarlo B, Kennedy A, Giuliano A, Calfa C, Molthrop D, Mani A, Chen HW, Dering J, Adams B, Kotler E, Press MF, Brugge JS, Curtis C, Slamon DJ. Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07). Nat Commun. 2020 Nov 17;11(1):5824. doi: 10.1038/s41467-020-19494-2.

Reference Type: DERIVED

PMID: 33203854 (View on PubMed)

Other Identifiers

P30CA016042

Identifier Type: NIH

Identifier Source: secondary_id

View Link

TRIO-TORI-B-07

Identifier Type: -

Identifier Source: secondary_id

SANOFI-AVENTIS-TRIO-TORI-B-07

Identifier Type: -

Identifier Source: secondary_id

WIRB-20080822

Identifier Type: -

Identifier Source: secondary_id

CDR0000616008

Identifier Type: -

Identifier Source: org_study_id

NCT02668939

Identifier Type: -

Identifier Source: nct_alias