NSABP B-43-CC - "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"
 

Treatment Plan    (Supplied Drug:  Trastuzumab)

Group 1*

RT (WBI):  25+ fx or accelerated fractionation (16-17 fx)**

Group 2*

RT (WBI):  25+ fx or accelerated fractionation (16-17 fx)**

Trastuzumab (Dose 1):  8mg/kg, IV over 90 mins***

Trastuzumab (Dose 2):  6mg/kg, IV over 30 mins (3 wks following Dose 1)

*        ER+ &/or PgR+ pts should receive >5 yrs hormonal therapy.

**    Boost, including brachytherapy, at Rad Onc's discretion.

***    If RT planned for 25+ fx:  Administer w/i 1 wk b/f RT begins or w/i 1st 5 days of RT (on or b/f Day 5)

        If RT planned for 16-17 fx:  Administer w/i 1 wk b/f RT begins or w/i 1st 2 days of RT (on or b/f Day 2)

Eligibility

• Female, age >18.

• ECOG perf status 0-1.

• On histol exam, tumor must be DCIS (mixed DCIS & LCIS is allowed).

• DCIS must be HER2+ by central testing.

• ER &/or PgR status must be determined pre-randomiz.  DCIS that is hormone receptor positive or negative is allowed.

• All DCIS must have been resected by lumpectomy.

• Margins of resected specimen must be histologically free of DCIS.  Re-excision(s) may be performed to obtain clear margins.  No pts requiring mastectomy.

• If axillary staging is performed, must be pN0(i-), pN0(i+) - [isolated tumor cells <0.2mm regardless of method of detection], pN0(mol-), or pN0(mol+).  Axillary staging not required.  See protocol for detailed staging information.

• <120 days between last surgery for excision of DCIS & randomiz.

• No invasive (including T1mic) breast cancer.  DCIS "suspicious" for microinvasion, but not confirmed, is allowed.

• No DCIS in >1 quadrant (multicentric).

• No masses or clusters of calcification that are clinically or mammographically suspicious unless biopsied & proven benign.  If DCIS is found, pt is eligible if DCIS was in same quadrant of ipsilateral breast and was resected w/clear margins.

• No contralateral breast cancer (including DCIS).

• No WBI administered b/f randomiz.  No partial breast RT allowed.

• No hx of breast cancer, including DCIS.  Hx of LCIS is allowed.

• No prior anthracycline chemo for any malignancy.

• No cardiac disease to preclude use of study drugs.  Includes (but not confined to):

  Active cardiac disease

  • Angina pectoris requiring anti-anginal meds

  • Ventricular arrhythmia except for benign PVCs controlled by meds

  • Conduction abnormality requiring pacemaker

  • Supraventricular and nodal arrhythmias requiring pacemaker or not controlled w/meds

  • Clinically significant valvular disease

  Hx of cardiac disease

  • MI documented by elevated cardiac enzymes or persistent regional wall abnormalities on LV function asmt

  • Documented CHF

  • Documented cardiomyopathy

• No uncontrolled HTN (systolic >180mm/Hg &/or diastolic >100mm/Hg (unless well controlled on meds).

• No other non-malig systemic disease to preclude use of Trastuzumab or RT, or prevent prolonged follow-up.

• No other malignancies unless disease-free >5 yrs pre-randomiz & at low risk for recurrence (physician's opinion).  Following cancers are allowed if diagnosed & treated w/i past 5 yrs:  In situ  carcinomas (cervix, colon, or melanoma) or non-melanoma skin cancer.

• No pregnant or nursing women at study entry.

• No investigational agent use w/i 30 days pre-study entry.

• PRESTUDY REQUIREMENTS (w/i 3 mos pre-randomiz unless otherwise specified):

  • H&P (physician or other healthcare professional from RO or dept administering Trastuzumab), ht, wt

  • Rad Onc eval

  • Menopausal status (w/i 1 mo pre-randomiz)

  • Menstrual hx  (w/i 1 mo pre-randomiz)

  • Bilat mammogram (w/i 6 mos pre-randomiz) - MRI not permitted as substitute

  • Pregnancy test (if applicable, w/i 2 wks pre-randomiz)

  • Tumor block submission for central HER2 testing (PRE-RANDOMIZ TO DETERMINE ELIGIBILITY - MANDATORY)*

  *     Ship via overnight delivery to:  Rush Univ. Medical Center; ATTN:  Rosalie Perez (NSABP B-43 TRIAL).

• Signed informed consent.