Abstract OT1-05-04: Phase 3 trial of

ca

rboplatin in

t

riple negative breast cancer (TNBC) patients with residual invasive carcinoma after neoadjuvant chemotherapy (

J

ONIE4:J-CAT trial)
Authors: Tanino H , Suzuki M , Kaise H , Miyashita M , Chishima T , Hayashi M , Miyoshi Y , Futamura M , Ohtani S , Nagahashi M , Ohta T , Kosaka Y , Ishikawa T , Hasegawa Y , Kubota T , Sangai T , Iwatani T , Yamada A , Akazawa K , Kohno N 
Published: May 2019

Background: It is well known that the prognosis of non pCR TNBC patients was poor after anthracycline and taxan treatment. For such patients, capecitabine seems to be effective to reduce recurrence based on the HR 0.58 of the CREATE X trial (Masuda, N. et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 376, 2147. 2017) . However, the target of capecitabine is still unclear for TNBC. We classified non pCR tumors as BRCAness and Sporadic using BRCAness test(MRC-Holland, Amsterdam, the Netherlands). The recurrence rate of the BRCAness group was about 70%. Carboplatine is expected to be effective against BRCAness tumors, as it is a DNA damaging agent. In this study BRCAness can be checked just before carboplatin treatment using surgical specimens. Then the efficacy of carboplatin will be directly known to make comparison between DFS in the carboplatin group and that of the observation group.

Trial design: This is anopen label, randomized phase III study that will enroll TNBC with residual invasive cancer after surgery with preoperative chemotherapy including both anthracycrine and taxan. Patients are randomly assigned to either the carboplatin group or observation group. The patients in the carboplatin group are treated with carboplatin at AUC 6 and those in the observation group are observed at only 3 years.

Eligibility criteria:

1) ER and PgR&lt;1%, HER2 0, 1+ or 2+ with FISH negative on core needle biopsy before the chemotherapy and surgical specimens.

2) Preoperative chemotherapy including both anthracycrine and taxan.

3) Residual invasive cancer on breast tumors or lymph node metastasis in surgical specimens.

4) 20-79 year old women.

5) No chemotherapy within 5 years.

6) Not bilateral breast cancer, without metastasis, no prior breast cancer.

7) No severe bone marrow suppression.

Specific aims:Primary objective is DFS (Disease Free Survival). Secondary objectives are overall survival and safety.

STATISTICAL METHODS:

The 3 years recurrence rate of the observation group was estimated as 40% and hazard ratio at 0.58 based on the CREATE X trial. For both groups, 135 patients are necessary. This study is powered to approximately 80% to test the superiority of carboplatin group at a 2-sided α=0.05 using a stratified log-rank test.

Activation Date:22ndMarch 2018. No patients had been enrolled till 3rd July.

Citation Format: Tanino H, Suzuki M, Kaise H, Miyashita M, Chishima T, Hayashi M, Miyoshi Y, Futamura M, Ohtani S, Nagahashi M, Ohta T, Kosaka Y, Ishikawa T, Hasegawa Y, Kubota T, Sangai T, Iwatani T, Yamada A, Akazawa K, Kohno N. Phase 3 trial of carboplatin in triple negative breast cancer (TNBC) patients with residual invasive carcinoma after neoadjuvant chemotherapy (JONIE4:J-CAT trial) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-05-04.