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

• ClinicalTrials.gov Identifier: NCT00769379
• Recruitment Status: Active, not recruiting
• First Posted: October 9, 2008
• Results First Posted: February 23, 2022
• Last Update Posted: May 2, 2022
• Sponsor: National Cancer Institute (NCI)
• Collaborator: NRG Oncology
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Ductal Carcinoma In Situ
• Interventions: Other: Laboratory Biomarker Analysis; Biological: Trastuzumab; Radiation: Whole Breast Irradiation
• Enrollment: 2014

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm I (Standard WBI)	Arm II (WBI, Trastuzumab)
Arm/Group Description	Patients undergo standard WBI over 5-6 weeks. Laboratory Biomarker Analysis: Correlative studies Whole Breast Irradiation: Undergo standard whole breast irradiation	Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. Laboratory Biomarker Analysis: Correlative studies Trastuzumab: Given IV Whole Breast Irradiation: Undergo standard whole breast irradiation
Period Title: Overall Study
Started	1008	1006
Completed	1005	993
Not Completed	3	13
Reason Not Completed
No follow up data mapped to Other.	3	13

Baseline Characteristics

Arm/Group Title		Standard WBI	WBI, Trastuzumab	Total
Arm/Group Description		Standard WBI (Radiation Therapy)	WBI, trastuzumab (Radiation Therapy + Trastuzumab x 2 doses. Dose 1: 8 mg/kg IV Dose 2: 6 mg/kg IV-given 3 weeks after dose 1	Total of all reporting groups
Overall Number of Baseline Participants		1008	1006	2014
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1008 participants	1006 participants	2014 participants
		56 (9.3)	56 (8.7)	56 (9.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1008 participants	1006 participants	2014 participants
	Female	1008 100.0%	1006 100.0%	2014 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1008 participants	1006 participants	2014 participants
	American Indian or Alaska Native	5 0.5%	5 0.5%	10 0.5%
	Asian	33 3.3%	43 4.3%	76 3.8%
	Native Hawaiian or Other Pacific Islander	4 0.4%	4 0.4%	8 0.4%
	Black or African American	59 5.9%	58 5.8%	117 5.8%
	White	893 88.6%	885 88.0%	1778 88.3%
	More than one race	4 0.4%	1 0.1%	5 0.2%
	Unknown or Not Reported	10 1.0%	10 1.0%	20 1.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	1008 participants	1006 participants	2014 participants
Latino		45 4.5%	47 4.7%	92 4.6%
Non-Latino		925 91.8%	920 91.5%	1845 91.6%
Unknown		38 3.8%	39 3.9%	77 3.8%

Outcome Measures

1. Primary Outcome

Title	Ipsilateral Invasive Breast Cancer, Ipsilateral Skin Cancer Recurrence, or Ipsilateral DCIS-Free Survival
Description	Patients who are free from Ipsilateral Invasive Breast Cancer, Ipsilateral Skin Cancer Recurrence or Ipsilateral DCIS as estimated by (1- cumulative incidence) x 100%.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Standard WBI)	Arm II (WBI, Trastuzumab)
Arm/Group Description:	Patients undergo standard WBI over 5-6 weeks. Laboratory Biomarker Analysis: Correlative studies Whole Breast Irradiation: Undergo standard whole breast irradiation	Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. Laboratory Biomarker Analysis: Correlative studies Trastuzumab: Given IV Whole Breast Irradiation: Undergo standard whole breast irradiation
Overall Number of Participants Analyzed	1005	993
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients event free
	95.1; (93.8 to 96.5)	96.1; (94.9 to 97.3)

2. Secondary Outcome

Title	Invasive or DCIS Disease-free Survival
Description	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. Percentage of patients by a Kaplan-Meier analysis who are free of invasive or DCIS disease
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Standard WBI)	Arm II (WBI, Trastuzumab)
Arm/Group Description:	Patients undergo standard WBI over 5-6 weeks. Laboratory Biomarker Analysis: Correlative studies Whole Breast Irradiation: Undergo standard whole breast irradiation	Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. Laboratory Biomarker Analysis: Correlative studies Trastuzumab: Given IV Whole Breast Irradiation: Undergo standard whole breast irradiation
Overall Number of Participants Analyzed	1005	993
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients event free
	88.4; (86.3 to 90.4)	90.6; (88.8 to 92.5)

3. Secondary Outcome

Title	Invasive or DCIS Recurrence-free Interval
Description	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.Percentage of patients who are invasive or DCIS recurrence free estimated by (1-cumulative incidence) x 100%.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Standard WBI)	Arm II (WBI, Trastuzumab)
Arm/Group Description:	Patients undergo standard WBI over 5-6 weeks. Laboratory Biomarker Analysis: Correlative studies Whole Breast Irradiation: Undergo standard whole breast irradiation	Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. Laboratory Biomarker Analysis: Correlative studies Trastuzumab: Given IV Whole Breast Irradiation: Undergo standard whole breast irradiation
Overall Number of Participants Analyzed	1005	993
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients event free
	94.4; (92.9 to 95.8)	95.8; (94.5 to 97.1)

4. Secondary Outcome

Title	Invasive Regional or Distant-Free Recurrence
Description	Percentage of patients who are free of invasive regional or distant recurrence as estimated by (1 - cumulative incidence) x 100%.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Standard WBI)	Arm II (WBI, Trastuzumab)
Arm/Group Description:	Patients undergo standard WBI over 5-6 weeks. Laboratory Biomarker Analysis: Correlative studies Whole Breast Irradiation: Undergo standard whole breast irradiation	Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. Laboratory Biomarker Analysis: Correlative studies Trastuzumab: Given IV Whole Breast Irradiation: Undergo standard whole breast irradiation
Overall Number of Participants Analyzed	1005	993
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients event free
	99.9; (99.7 to 100.0)	99.9; (99.7 to 100.0)

5. Secondary Outcome

Title	Contralateral Breast Cancer (Invasive or DCIS) - Free Survival
Description	Percentage of patients free of Contralateral Breast Cancer (Invasive or DCIS) as estimated by (1- cumulative incidence) x 100%.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Standard WBI)	Arm II (WBI, Trastuzumab)
Arm/Group Description:	Patients undergo standard WBI over 5-6 weeks. Laboratory Biomarker Analysis: Correlative studies Whole Breast Irradiation: Undergo standard whole breast irradiation	Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. Laboratory Biomarker Analysis: Correlative studies Trastuzumab: Given IV Whole Breast Irradiation: Undergo standard whole breast irradiation
Overall Number of Participants Analyzed	1005	993
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients event free
	97.9; (97.0 to 98.8)	98.4; (97.6 to 99.2)

6. Secondary Outcome

Title	Overall Survival
Description	Percentage of patients surviving as estimated by a Kaplan-Meier
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Standard WBI)	Arm II (WBI, Trastuzumab)
Arm/Group Description:	Patients undergo standard WBI over 5-6 weeks. Laboratory Biomarker Analysis: Correlative studies Whole Breast Irradiation: Undergo standard whole breast irradiation	Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. Laboratory Biomarker Analysis: Correlative studies Trastuzumab: Given IV Whole Breast Irradiation: Undergo standard whole breast irradiation
Overall Number of Participants Analyzed	1005	993
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients surviving
	98.9; (98.2 to 99.5)	99.0; (98.3 to 99.6)

7. Secondary Outcome

Title	Incidence of Post-treatment Amenorrhea in Women Who Were Premenopausal at the Time of Study Entry Premenopausal at the Time of Study Entry
Description	Proportion of patients who were pre-menopausal at randomization and who self-reported as not having menstrual periods afterwards
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All patients who reported being postmenopausal at randomization who later self-reported as yes or no to whether or not they had menstrual periods.

Arm/Group Title	Arm I (Standard WBI)	Arm II (WBI, Trastuzumab)
Arm/Group Description:	Patients undergo standard WBI over 5-6 weeks. Laboratory Biomarker Analysis: Correlative studies Whole Breast Irradiation: Undergo standard whole breast irradiation	Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. Laboratory Biomarker Analysis: Correlative studies Trastuzumab: Given IV Whole Breast Irradiation: Undergo standard whole breast irradiation
Overall Number of Participants Analyzed	126	121
Measure Type: Number; Unit of Measure: percentage of participants
	63	72

Adverse Events

Time Frame	All Cause Mortality-5 years: Adverse Events: While on study therapy, Day 1 of 1st dose through 30 days after Day 1 of last dose.
Adverse Event Reporting Description	All Cause mortality at 5-years is the proportion of all patients with follow-up information who have died within the first 5 years after randomization. Adverse event proportions only include patients who had reported AE forms during the period of 30 days after their 1st last dose of protocol therapy.
Arm/Group Title	Standard WBI	WBI, Trastuzumab
Arm/Group Description	standard WBI	WBI, trastuzumab
All-Cause Mortality
	Standard WBI	WBI, Trastuzumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	11/1005 (1.09%)	10/993 (1.01%)
Serious Adverse Events
	Standard WBI	WBI, Trastuzumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/998 (0.30%)	9/990 (0.91%)
Cardiac disorders
Atrial flutter † 1	0/998 (0.00%)	1/990 (0.10%)
Myocardial infarction † 1	1/998 (0.10%)	0/990 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	0/998 (0.00%)	1/990 (0.10%)
Hepatobiliary disorders
Cholecystitis † 1	0/998 (0.00%)	1/990 (0.10%)
Infections and infestations
Urinary tract infection † 1	0/998 (0.00%)	1/990 (0.10%)
Lung infection † 1	0/998 (0.00%)	1/990 (0.10%)
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify † 1	0/998 (0.00%)	1/990 (0.10%)
Investigations
Cardiac troponin I increased † 1	1/998 (0.10%)	0/990 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	0/998 (0.00%)	1/990 (0.10%)
Hyperglycemia † 1	0/998 (0.00%)	1/990 (0.10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1	0/998 (0.00%)	1/990 (0.10%)
Leukemia secondary to oncology chemotherapy † 1	1/998 (0.10%)	0/990 (0.00%)
Treatment related secondary malignancy † 1	2/998 (0.20%)	1/990 (0.10%)
Vascular disorders
Hypotension † 1	0/998 (0.00%)	1/990 (0.10%)
Thromboembolic event † 1	0/998 (0.00%)	1/990 (0.10%)
1 Term from vocabulary, CTCAE v4.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Standard WBI	WBI, Trastuzumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	292/998 (29.26%)	254/990 (25.66%)
General disorders
Fatigue † 1	80/998 (8.02%)	77/990 (7.78%)
Injury, poisoning and procedural complications
Dermatitis radiation † 1	261/998 (26.15%)	208/990 (21.01%)
1 Term from vocabulary, CTCAE v4.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Director, Department of Regulatory Affairs
• Organization: NRG Oncology
• Phone: 412-339-5300
• EMail: langerj@nrgoncology.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cobleigh MA, Anderson SJ, Siziopikou KP, Arthur DW, Rabinovitch R, Julian TB, Parda DS, Seaward SA, Carter DL, Lyons JA, Dillmon MS, Magrinat GC, Kavadi VS, Zibelli AM, Tiriveedhi L, Hill ML, Melnik MK, Beriwal S, Mamounas EP, Wolmark N. Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial. J Clin Oncol. 2021 Jul 20;39(21):2367-2374. doi: 10.1200/JCO.20.02824. Epub 2021 Mar 19.

Duggal S, Robin J, Julian TB. Ductal carcinoma in situ: an overview. Expert Rev Anticancer Ther. 2013 Aug;13(8):955-62. doi: 10.1586/14737140.2013.820557. Review.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00769379
• Other Study ID Numbers: NCI-2009-00702; NCI-2009-00702 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000615085; B-43; NSABP-B-43 ( Other Identifier: NRG Oncology ); NSABP-B-43 ( Other Identifier: CTEP ); U10CA012027 ( U.S. NIH Grant/Contract ); U10CA180868 ( U.S. NIH Grant/Contract )
• First Submitted: October 8, 2008
• First Posted: October 9, 2008
• Results First Submitted: March 23, 2021
• Results First Posted: February 23, 2022
• Last Update Posted: May 2, 2022