ABCSG 43/INSEMA Details

An open-label, multicenter, Phase IIIb study to assess the safety and efficacy of ribociclib (LEE011) in combination with letrozole for the treatment of men and pre/postmenopausal women with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior hormonal therapy for advanced disease.

Start:
03/2016
Status:
open
Sample size:
5.940 (1. Randomization, international);
1.968 (2. randomization, international), 800 (2. randomization, national)

Contact ABCSG-Trial office

E-mail: info@abcsg.at
Phone: +43 1 408 92 30
Fax: +43 1 409 09 90

Design:

Design ABCSG 43/INSEMA
(Click to enlarge)

Primary objective:

To compare the invasive disease-free survival after breast-conserving surgery (non-inferiority question)

  • no axillary surgery vs. SLNB patients (first randomization)
  • pN+(sn) with SLNB alone vs. pN+(sn) patients with completion ALND (second randomization)

Secondary objectives:

To compare invasive disease-free survival after breast-conserving surgery

  • no axillary surgery vs. pN0(sn) patients
  • no axillary surgery vs. pN+(sn) patients with SLNB alone
  • no axillary surgery vs. pN+(sn) patients with completion ALND

To compare overall survival between arms.

To compare locoregional disease-free survival (no tumor in the ipsilateral breast or ipsilateral supraclavicular, subclavicular, internal mammary or axillary nodes) between arms in both randomizations.

Ipsilateral axillary recurrence rate.

To compare distant disease-free survival between arms in both randomizations.

To compare the invasive disease-free survival between arms in subgroups according to age (<65 years vs. ≥65 years), tumor grading (G1/G2 vs. G3), tumor size (≤2 cm vs. >2 cm), delivered dose distribution in ipsilateral axilla levels I-III during postoperative whole-breast irradiation, and study site (German vs. Austrian sites in randomization 2).

To compare the safety and quality-of-life between arms and by subgroups.

Inclusion criteria:

  1. Written informed consent prior to beginning breast-conserving surgery, including expected cooperation of the patients for follow-up, must be obtained and documented according to the local regulatory requirements.
  2. Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy or open biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is planned.
  3. Age at diagnosis at least 18 years.
  4. Preoperative imaging techniques (mammography and sonography are mandatory) with estimated tumor size of ≤5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status).
  5. Clinically and sonographically tumor-free axilla prior to biopsy (cN0/iN0).
  6. In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration (FNA) biopsy of the sonographically suspected lymph node is required before randomization.
  7. No clinical evidence for distant metastasis (M0).
  8. Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation).

Exclusion criteria:

  1. History of malignancy within last 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix.
  2. Time since core/open biopsy >3 months (optimal <1 month).
  3. Previous and already (neoadjuvant) treated invasive breast carcinoma.
  4. Histologically non-invasive breast carcinoma.
  5. cT3/T4 or iT3/T4 tumors
  6. Pregnant or lactating patients.
  7. Planned total mastectomy.
  8. Planned intraoperative radiotherapy (e.g. Intrabeam) or postoperative partial breast irradiation (e.g. multicatheter technique) alone; both procedures are allowed as boost techniques.
  9. Male patients.