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Trastuzumab and External Beam Radiation Therapy in Treating Women With Stage III or Stage IV Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00943410
First received: July 21, 2009
Last updated: August 14, 2012
Last verified: August 2012
History of Changes
  Purpose

RATIONALE: 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Trastuzumab may make tumor cells more sensitive to radiation therapy. Giving trastuzumab together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving trastuzumab together with external beam radiation therapy works in treating women with stage III or stage IV breast cancer.


Condition Intervention Phase
Breast Cancer
 Radiation: external beam radiation therapy
Drug: Herceptin
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Herceptin Concurrent With External Beam Radiation Following Neoadjuvant Chemotherapy for the Treatment of HER2 Over-Expressing Breast Cancer

Resource links provided by NLM:

Drug Information available for: Trastuzumab
U.S. FDA Resources

Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of subjects experiencing adverse events [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]
    Toxicity (adverse events) will be measured and graded using the CTCAE criteria. RTOG acute toxicity criteria will be used to score acute radiation-related toxicity


Secondary Outcome Measures:
  • Pathologic response rate [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
    Pathological response will be measured for those subjects who are deemed surgical candidates. Pathologic response will be defined as invasive tumor present pathologically, or complete invasive tumor clearance (pCR), which includes those tumors with no tumor present as well as those tumors with only in situ carcinoma present after all therapy

  • Locoregional recurrence rate [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    Radiographic response and recurrence rate will captured using RECIST criteria. Subjects will be followed up for 5 years to document recurrence.

  • Time to locoregional recurrence [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Radiographic response and recurrence rate will captured using RECIST criteria. Subjects will be followed up to 5 years to document recurrence

  • Time to local progression (in patients who are deemed to be non-surgical candidates) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Radiographic response and recurrence rate will captured using RECIST criteria. Disease progression is defined as an increase in the product of two perpendicular diameters of any measured lesion by > 25% over the size at study entry or the appearance of new areas of malignant disease


Enrollment: 19
Study Start Date: March 2000
Study Completion Date: July 2009
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Surgical Candidate
After 5 consecutive weeks of treatment with Radiation and Herceptin, these subjects will receive mastectomy excision
 Radiation: external beam radiation therapy
Radiation therapy will consist of 50Gy in 2Gy fractions to the breast/chest wall and regional lymphatics for 5 consecutive days up to 5 weeks for surgical candidates and 7 weeks for non-surgical candidates
Drug: Herceptin
Patients who are already receiving weekly Herceptin® will continue weekly Herceptin®, 2mg/kg IV on day 1 of each week of radiotherapy. Patients who have not been receiving weekly Herceptin® as a component of systemic therapy will begin Herceptin® one week prior to beginning radiotherapy with a loading dose of 4mg/kg followed by weekly Herceptin® at 2mg/kg on day 1 of each week of radiotherapy
Active Comparator: Non-Surgical Candidate
After 5 weeks of consecutive treatment with radiation and herceptin, these subjects will not be eligible for surgery. They will continue with radiation and herceptin for an additional 2 weeks.
 Radiation: external beam radiation therapy
Radiation therapy will consist of 50Gy in 2Gy fractions to the breast/chest wall and regional lymphatics for 5 consecutive days up to 5 weeks for surgical candidates and 7 weeks for non-surgical candidates
Drug: Herceptin
Patients who are already receiving weekly Herceptin® will continue weekly Herceptin®, 2mg/kg IV on day 1 of each week of radiotherapy. Patients who have not been receiving weekly Herceptin® as a component of systemic therapy will begin Herceptin® one week prior to beginning radiotherapy with a loading dose of 4mg/kg followed by weekly Herceptin® at 2mg/kg on day 1 of each week of radiotherapy

Detailed Description:

OBJECTIVES:

Primary

  • Determine the tolerability of trastuzumab (Herceptin®) and concurrent external beam radiotherapy in women with HER2-overexpressing stage III or IV breast cancer.

Secondary

  • Determine the pathologic response rate in patients treated with this regimen.
  • Determine the locoregional recurrence rate (as site of first recurrence or any recurrence) and time to locoregional recurrence in patients treated with this regimen.
  • Determine the time to local progression in patients (who are deemed to be non-surgical candidates) treated with this regimen .

OUTLINE: This is a multicenter study.

Patients receive trastuzumab IV over 30-90 minutes once a week for 5 weeks. Patients also undergo external beam radiotherapy once daily 5 days a week for 5 weeks.

Three weeks after the completion of trastuzumab and radiotherapy, patients undergo surgical evaluation. Patients deemed to be surgical candidates undergo surgery. Patients deemed to be non-surgical candidates continue to receive trastuzumab and external beam radiotherapy for 2 additional weeks.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* invasive primary carcinoma of the breast by fine-needle aspiration, core needle biopsy, or incisional biopsy
  • Excisional biopsy is not allowed

  • Stage III or IV disease (clinical and radiographic staging), including any of the following:

    • Any T with N2 disease (metastasis to ipsilateral axillary lymph nodes fixed to one another or other structures) or N3 disease (metastasis to ipsilateral internal mammary lymph nodes)
    • T4, any N disease
    • Inflammatory disease
    • Supraclavicular and/or infraclavicular adenopathy
    • Distant metastasis with measurable disease in the breast or lymph nodes
  • HER2-overexpressing tumor
  • Measurable or evaluable disease
  • Residual locoregional disease after completion of neoadjuvant chemotherapy OR locoregional recurrent disease
  • Synchronous bilateral primary cancers allowed provided the more serious of the two cancers meets staging criteria
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • WBC > 2,000/mm^3
  • Platelet count > 50,000/mm^3
  • Hemoglobin > 11 g/dL
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Radionucleotide ventriculography/LVEF normal OR ≤ 10% asymptomatic decline from baseline after completion of neoadjuvant chemotherapy

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior radiotherapy to the breast or regional lymph nodes
  • Concurrent participation in neoadjuvant chemotherapy clinical trials allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00943410

Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Carolyn Sartor, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00943410     History of Changes
Obsolete Identifiers: NCT00006109
Other Study ID Numbers: LCCC 9925, CDR000649128
Study First Received: July 21, 2009
Last Updated: August 14, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
HER2-positive breast cancer
inflammatory breast cancer
recurrent breast cancer
stage IIIA breast cancer
 stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
 Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013