Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer (Subito)

Netherlands Cancer Institute (NKI)

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer

Treatments: Drug: ddAC-mini CTC; Drug: ddAC-CP-Olaparib

Study type: Interventional

Funder types: Other

Identifiers

NCT02810743

M16BRC

Details and patient eligibility

About

Investigator-initiated, international, multicentre, randomized, open-label, (neo)adjuvant phase III study in target population (stage III, HER2-negative, BRCA1-like breast cancer patients) comparing optimized standard-dose chemotherapy with intensified, alkylating chemotherapy with stem cell rescue.

Enrollment: 174 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women and men with stage III adenocarcinoma of the breast harboring signs of a breast cancer with features of homologous recombination deficiency (HRD)
• Age of 18-65 years
• The tumor must be HER2-negative
• Treatment must start within 8 weeks after the last surgical resection
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Exclusion criteria

• Previous radiation therapy
• Previous chemotherapy
• Any previous treatment with a PARP-inhibitor, including olaparib
• Pre-existing neuropathy from any cause in excess of Grade 1
• Chronic concomitant use of known strong or moderate CYP3A inducers

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

174 participants in 2 patient groups

ddAC-CP-Olaparib

Active Comparator group

Description:

ddAC; doxorubicin 60 mg/m² as an i.v. bolus and cyclophosphamide 600 mg/m² as an i.v. bolus on day 1 every 2 weeks ddAC must be supported with prophylactic pegfilgrastim 6 mg s.c. given 24-48 hours after completion of administration of EVERY chemotherapy cycle CP; carboplatin/paclitaxel (CP) consisting of carboplatin (AUC 6) on day 1 and paclitaxel (80 mg/m2) on day 1,8 and 15 of a 21 days cycle. In total 4 courses of CP will be administered. Olaparib will be administered in Dutch centers only, as monotherapy for one year at a dose of 300 mg BID, starting 3 weeks after adjuvant radiotherapy, or, if radiotherapy is not indicated, 3-5 weeks after the last CP cycle. Patients without a (near) pCR will receive adjuvant capecitabine at a starting dose of 1000-1250 mg/m2, twice a day, on days 1-14 every 3 weeks for eight cycles.

Treatment:

Drug: ddAC-CP-Olaparib

ddAC-mini CTC

Active Comparator group

Description:

ddAC; doxorubicin 60 mg/m² as an i.v. bolus and cyclophosphamide 600 mg/m² as an i.v. bolus on day 1 every 2 weeks ddAC must be supported with prophylactic pegfilgrastim 6 mg s.c. given 24-48 hours after completion of administration of EVERY chemotherapy cycle intensified alkylating 'mini' CTC (2x) cyclophosphamide 3000 mg/m2 day 1 mesna 500 mg (push) + 2000 mg in 24 hours day 1 carboplatin (400 mg/m2; (or AUC=5 in patients with a calculated creatinine-clearance of \<100 ml/min)) days 1,2 thiotepa 250 mg/m2 day 2 Patients without a (near) pCR will receive adjuvant capecitabine at a starting dose of 1000-1250 mg/m2, twice a day, on days 1-14 every 3 weeks for eight cycles.

Treatment:

Drug: ddAC-mini CTC