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RANDOMIZED PHASE III TRIAL OF PACLITAXEL + TRASTUZUMAB + LAPATINIB VERSUS PACLITAXEL + TRASTUZUMAB AS NEOADJUVANT TREATMENT OF HER2-POSITIVE PRIMARY BREAST CANCER


Phase 3
18 Years
N/A
Open (Enrolling)
Both
HER2-positive Breast Cancer, Male Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

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Trial Information

RANDOMIZED PHASE III TRIAL OF PACLITAXEL + TRASTUZUMAB + LAPATINIB VERSUS PACLITAXEL + TRASTUZUMAB AS NEOADJUVANT TREATMENT OF HER2-POSITIVE PRIMARY BREAST CANCER


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 AJCC TMN
criteria (Version 6), to neoadjuvant weekly paclitaxel plus 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. OS and TFF will be measured for all patients from study
registration. RFS will be measured from definitive surgery for those patients who undergo
definitive surgery.

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.


Inclusion Criteria:



- Pathologically confirmed invasive breast cancer by core needle or incisional biopsy

- Clinical stage II or III disease

- Resectable disease

- HER2- positive tumor, defined as 3+ over expression by immunohistochemistry (IHC) or
gene amplification by fluorescence in situ hybridization (FISH) with a ratio of >= 2
on invasive tumor

- Measurable disease, defined as target lesion in the breast >= 1 cm by physical
examination or radiographic measurement

- No axillary disease only

- Multicentric or bilateral disease allowed provided the target lesion meets
eligibility criteria

- Planning to undergo surgical resection after neoadjuvant therapy

- No inflammatory breast cancer

- No metastatic disease

- Concurrent enrollment in CALGB-150702 required

- Hormone receptor status known

- Menopausal status not specified

- Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1

- Absolute neutrophil count (ANC) >= 1,000/mm^3

- Platelet count >= 100,000/mm^3

- Bilirubin =< 1.5 times upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective non-hormonal contraception during and for >= 2
months after completion of study treatment

- Cardiac ejection fraction >= 50% by echocardiogram or multiple gated acquisition
(MUGA) scan

- Willing to undergo pretreatment biopsies and submit archival tissue obtained at the
time of surgery

- No concurrent pegfilgrastim

- No prior chemotherapy, hormonal therapy, biologic therapy, or radiotherapy for the
treatment of breast cancer

- No other concurrent chemotherapy or hormonal therapy, except for the following:

- Steroids for adrenal failure

- Hormones for non-disease-related conditions (e.g., insulin for diabetes)

- Intermittent use of dexamethasone as an antiemetic

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pathologic complete response (pCR)

Outcome Time Frame:

At time of surgery

Safety Issue:

No

Principal Investigator

Lisa Carey

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01073

NCT ID:

NCT00770809

Start Date:

December 2008

Completion Date:

Related Keywords:

  • HER2-positive Breast Cancer
  • Male Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male

Name

Location
Cancer and Leukemia Group B Chicago, Illinois  60606