Clinical Trial: Radiation Therapy With or Without Trastuzumab in Treating Women With Ductal Carcinoma In Situ Who Have Undergone Lumpectomy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently With Radiation Therapy and Radiation Therapy Alone for Women With HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy

Brief Summary: This randomized phase III trial studies radiation therapy to see how well it works with or without trastuzumab in treating women with ductal carcinoma in situ who have undergone lumpectomy. 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. It is not yet known whether radiation therapy is more effective with or without trastuzumab in treating ductal carcinoma in situ.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the value of trastuzumab given during radiation therapy (RT) compared to RT alone in preventing subsequent occurrence of ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (IIBCR-SCR-DCIS) in women with human epidermal growth factor receptor 2 (HER2)-positive DCIS resected by lumpectomy.

SECONDARY OBJECTIVES:

I. Determine the value of trastuzumab given during RT compared to RT alone in prolonging invasive or DCIS disease-free survival (IDFS)-DCIS.

II. Determine the value of trastuzumab given during RT compared to RT alone in increasing invasive or DCIS recurrence-free interval.

III. Determine the value of trastuzumab given during RT compared to RT alone in improving regional or distant recurrence.

IV. Determine the value of trastuzumab given during RT compared to RT alone in improving the incidence of contralateral invasive or DCIS breast cancer.

V. Determine the value of trastuzumab given during RT compared to RT alone in improving survival.

VI. To explore the effect of trastuzumab on ovarian function.

TERTIARY OBJECTIVES:

I. To determine if the benefit of trastuzumab added to RT will be significantly higher in v-myc avian myelocytomatosis viral oncogene homolog (cMYC)-amplified tumors than in the cMYC non-amplified subset.

II. To determine if the benefit of trastuzumab added to RT w
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Time from randomization to ipsilateral invasive breast cancer, ipsilateral skin cancer recurrence, or ipsilateral DCIS [ Time Frame: Up to 10 years ]

Original Primary Outcome: Time from randomization to ipsilateral invasive breast cancer, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (DCIS)

Current Secondary Outcome:

• Contralateral breast cancer (invasive or DCIS) [ Time Frame: Time from randomization to first diagnosis of contralateral invasive or DCIS breast cancer, assessed up to 10 years ]
  Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.
• Incidence of post-treatment amenorrhea (absence of menstrual period for at least 12 months) in women who were premenopausal at the time of study entry [ Time Frame: 18 months ]
  Amenorrhea will be summarized by treatment arm in terms of incidence rates and the ranges, medians, and quantiles of duration.
• Invasive or DCIS disease-free survival [ Time Frame: Up to 10 years ]
  Events for analysis of IDFS-DCIS include: local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer (other than squamous and basal cell carcinoma of the skin, melanoma in situ, and carcinoma in situ of the colon and cervix), or death from any cause prior to recurrence or second primary cancer. Invasive breast cancer, ipsilateral recurrence, and contralateral breast cancer will be compared across treatment arms using cumulative incidence functions.
• Invasive or DCIS recurrence-free interval [ Time Frame: Time from randomization to first diagnosis of a local, regional or distant recurrence regardless of any intervening contralateral or other second primary cancer, assessed up to 10 years ]
  Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.
• Invasive regional or distant recurrence [ Time Frame: Time from randomization to first diagnosis of regional or distant recurrence, assessed up to 10 years ]
  Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.
• Overall survival [ Time Frame: Time from randomization to death from any cause, assessed up to 10 years ]
  Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.

Original Secondary Outcome:

• Invasive or DCIS disease-free survival as assessed by time to local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer (other than squamous cell and b ...
• Time from randomization to first diagnosis of a local, regional or distant recurrence regardless of any intervening contralateral or other second primary cancer
• Time from randomization to first diagnosis of regional or distant recurrence
• Time from randomization to first diagnosis of contralateral invasive or DCIS breast cancer
• Time from randomization to death from any cause
• Incidence of post-treatment amenorrhea (absence of menstrual period for at least 12 months) at 18 months in women who were premenopausal at the time of study entry
• Correlation of cMYC-amplification status with trastuzumab (Herceptin®) in addition to radiotherapy
• Correlation of PI3 kinase gene mutation status with trastuzumab in addition to radiotherapy

Dates:
Date Received: October 8, 2008
Date Started: November 2008
Date Completion:
Last Updated: May 18, 2017
Last Verified: May 2017