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Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00770809
Recruitment Status : Active, not recruiting
First Posted : October 10, 2008
Results First Posted : May 27, 2015
Last Update Posted : March 2, 2022
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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Brief Summary:
This randomized phase III trial studies paclitaxel and trastuzumab with or without lapatinib to see how well they work in treating patients with stage II or stage III breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. Giving paclitaxel with trastuzumab and/or lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which regimen is more effective in treating patients with breast cancer.

Condition or disease Intervention/treatment Phase
Male Breast Carcinoma Stage IIA Breast Cancer AJCC v6 and v7 Stage IIB Breast Cancer AJCC v6 and v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7 Other: Laboratory Biomarker Analysis Drug: Lapatinib Ditosylate Drug: Paclitaxel Biological: Trastuzumab Phase 3

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine if the pathologic complete response (pCR) in the breast to neoadjuvant weekly paclitaxel with trastuzumab plus lapatinib (THL) is 20% greater than the pCR to weekly paclitaxel with trastuzumab alone (TH).

SECONDARY OBJECTIVES:

I. To determine the pathologic complete response in the breast and axilla, using American Joint Committee on Cancer (AJCC) Tumor, Lymph Nodes and Metastasis (TMN) criteria (version 6), to neoadjuvant weekly paclitaxel plus human epidermal growth factor 2 (HER2)- targeted therapy in patients with HER2-positive operable breast cancer.

II. To evaluate residual cancer burden (RCB) as a predictor of long term relapse free survival (RFS) and overall survival (OS).

III. To document the toxicity of all chemotherapeutic regimens (THL, TH). IV. To determine the correlation between clinical, radiographic and pathologic response.

V. To compare overall survival (OS), relapse free survival (RFS) and time to first failure (TFF) among the treatment groups.

VI. To obtain blood, fresh frozen and fixed tumor tissue to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in blood, serum and tissue that are likely to influence response to and toxicity of trastuzumab alone or trastuzumab plus lapatinib, when given with paclitaxel.

VII. To determine the surgical practice patterns for breast conservation and sentinel lymphadenectomy in patients undergoing neoadjuvant chemotherapy.

VIII. To determine the radiotherapy practice patterns for post-mastectomy and regional nodal irradiation in patients undergoing neoadjuvant chemotherapy.

IX. To evaluate pharmacogenomic determinants of toxicity.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive trastuzumab IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and lapatinib ditosylate orally (PO) once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive trastuzumab and paclitaxel as in arm I.

ARM III: Patients receive paclitaxel and lapatinib ditosylate as in arm I. (Discontinued as of 6-15-11) Within 42 days after completion of neoadjuvant therapy, patients in both arms undergo definitive surgery (breast conservation or total mastectomy).

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 10 years.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 305 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial of Paclitaxel +Trastuzumab + Lapatinib Versus Paclitaxel + Trastuzumab as Neoadjuvant Treatment of HER2-Positive Primary Breast Cancer
Actual Study Start Date : December 1, 2008
Actual Primary Completion Date : January 31, 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm I (THL)
Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.
 Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lapatinib Ditosylate
Given PO
Other Name: Tykerb

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Biological: Trastuzumab
Given IV
Other Names:
  • ABP 980
  • ALT02
  • Anti-c-ERB-2
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Anti-p185-HER2
  • c-erb-2 Monoclonal Antibody
  • HER2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • Herzuma
  • Kanjinti
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • Ogivri
  • Ontruzant
  • PF-05280014
  • rhuMAb HER2
  • RO0452317
  • SB3
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar ALT02
  • trastuzumab biosimilar EG12014
  • Trastuzumab Biosimilar HLX02
  • Trastuzumab Biosimilar PF-05280014
  • Trastuzumab Biosimilar SB3
  • Trastuzumab Biosimilar SIBP-01
  • Trastuzumab-anns
  • Trastuzumab-dkst
  • Trastuzumab-dttb
  • Trastuzumab-pkrb
  • Trastuzumab-qyyp
  • Trazimera
Active Comparator: Arm II (TH)
Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.
 Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Biological: Trastuzumab
Given IV
Other Names:
  • ABP 980
  • ALT02
  • Anti-c-ERB-2
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Anti-p185-HER2
  • c-erb-2 Monoclonal Antibody
  • HER2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • Herzuma
  • Kanjinti
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • Ogivri
  • Ontruzant
  • PF-05280014
  • rhuMAb HER2
  • RO0452317
  • SB3
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar ALT02
  • trastuzumab biosimilar EG12014
  • Trastuzumab Biosimilar HLX02
  • Trastuzumab Biosimilar PF-05280014
  • Trastuzumab Biosimilar SB3
  • Trastuzumab Biosimilar SIBP-01
  • Trastuzumab-anns
  • Trastuzumab-dkst
  • Trastuzumab-dttb
  • Trastuzumab-pkrb
  • Trastuzumab-qyyp
  • Trazimera
Experimental: Arm III (TL)
Patients receive paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
 Drug: Lapatinib Ditosylate
Given PO
Other Name: Tykerb

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat


Outcome Measures
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Primary Outcome Measures :
  1. pCR Rate [ Time Frame: At time of surgery ]
    Complete pathological response is defined as the absence of residual invasive carcinoma in the breast at the time of definitive surgical removal. Pathologic complete response in the lymph nodes is defined as no detectable invasive tumor by H&E. Analysis will use a chi-square test for the difference in proportions of patients on the THL arm versus the TH arm who achieve a pCR. Exact binomial methods will be used to construct 95% confidence intervals around the pCR incidence for each arm.


Secondary Outcome Measures :
  1. Pathologic Stage in the Breast and Axilla [ Time Frame: At time of surgery ]
    Stage will be determined by the American Joint Committee on Cancer (AJCC) TNM (tumor, lymph nodes, metastasis) staging system.

  2. Radiographic Response Rate (at Completion of Neoadjuvant Therapy) [ Time Frame: Week 16 ]
    Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a complete response (disappearance of all target lesions) or partial response (30% decrease in sum of longest diameter of target lesions).

  3. Overall Survival [ Time Frame: Time from randomization to death or last follow-up (up to 10 years) ]
    Overall survival was measured as the interval from study entry until death, from any cause, or last contact. Distribution was estimated using the Kaplan Meier product-limit method

  4. Relapse-free Survival (RFS) [ Time Frame: Time from surgery to any recurrence (up to 10 years) ]
    Relapse free survival is defined as the interval from definitive surgery to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, or death from any cause, whichever occurs first. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Patients who do not undergo definitive surgery will not be assessable for RFS. Distribution was estimated using the Kaplan Meier product-limit method.

  5. Time to First Failure [ Time Frame: Time from study entry to any recurrence ( up to 10 years) ]
    Time to first failure is defined as the interval from study entry to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence or death from any cause. Patients who have not experienced any of these events will be censored at the date of last clinical assessment. Distribution was estimated using the Kaplan Meier product-limit method.

  6. Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3 [ Time Frame: Up to 30 days post-treatment ]
    The type and grade of treatment-related toxicity will be tabulated by treatment arm.


Eligibility Criteria
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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologic confirmation of invasive breast cancer; patients with inflammatory breast cancer are not eligible

  • Clinical stage II-III operable invasive breast cancer with intent to perform surgical resection after neoadjuvant therapy

    • Patients with multicentric or bilateral disease are eligible as long as the target lesion meets the eligibility criteria for this study
    • Staging to rule out metastatic disease is recommended for clinical stage III patients
  • Tumors must be HER2 positive defined as HER2 3+ by immunohistochemical (IHC) assays or gene amplification by fluorescence in situ hybridization (FISH) with a ratio of >= 2 on invasive tumor
  • Estrogen receptor (ER) and progesterone receptor (PgR) status must be known
  • The target lesion in the breast must be >= 1 cm on physical examination or by radiographic measurement; palpable axillary adenopathy will be documented but not serve as measurable disease for the primary endpoint; patients with axillary disease only are not eligible to participate
  • Patient agrees to provide pretreatment biopsies
  • No prior chemotherapy, hormone therapy, biologic, or radiation therapy with therapeutic intent for this cancer
  • Cardiac ejection fraction must be >= 50% by echocardiogram or multiple gated acquisition (MUGA) scan
  • Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
  • Patients must not be pregnant or nursing
  • Absolute neutrophil count (ANC) >= 1,000/ul
  • Platelet count >= 100,000/ul
  • Bilirubin =< 1.5 times upper limit of normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN)
  • Serum beta-human chorionic gonadotropin (HCG) negative (in female patients unless status-post (s/p) hysterectomy or menopausal or no menses for 24 consecutive months); assay must have a sensitivity of at least 50 mIU/mL
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00770809


Locations
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Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Lisa A Carey Alliance for Clinical Trials in Oncology
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00770809    
Other Study ID Numbers: NCI-2009-01073
NCI-2009-01073 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000616648
CALGB 40601 ( Other Identifier: Alliance for Clinical Trials in Oncology )
CALGB-40601 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA031946 ( U.S. NIH Grant/Contract )
First Posted: October 10, 2008    Key Record Dates
Results First Posted: May 27, 2015
Last Update Posted: March 2, 2022
Last Verified: October 2021
Additional relevant MeSH terms:
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Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Albumin-Bound Paclitaxel
Lapatinib
Trastuzumab biosimilar HLX02
Antineoplastic Agents, Immunological
Antibodies
 Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors