Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery
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| ClinicalTrials.gov Identifier: NCT00770809 |
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Recruitment Status :
Active, not recruiting
First Posted : October 10, 2008
Results First Posted : May 27, 2015
Last Update Posted : April 4, 2024
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| 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 |
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 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 |
| Estimated Study Completion Date : | July 10, 2024 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Other: Laboratory Biomarker Analysis
Correlative studies Drug: Lapatinib Ditosylate Given PO
Other Name: Tykerb Drug: Paclitaxel Given IV
Other Names:
Biological: Trastuzumab Given IV
Other Names:
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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.
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Other: Laboratory Biomarker Analysis
Correlative studies Drug: Paclitaxel Given IV
Other Names:
Biological: Trastuzumab Given IV
Other Names:
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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)
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Drug: Lapatinib Ditosylate
Given PO
Other Name: Tykerb Drug: Paclitaxel Given IV
Other Names:
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- 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.
- 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.
- 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).
- 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
- 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.
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Pathologic confirmation of invasive breast cancer; patients with inflammatory breast cancer are not eligible
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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
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
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| Principal Investigator: | Lisa A Carey | Alliance for Clinical Trials in Oncology |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | April 4, 2024 |
| Last Verified: | February 2024 |
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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, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Tyrosine Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors |