Clinical Trials /

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

NCT02810743

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02810743

Trial Eligibility

Document

Title

  • Brief Title: Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer
  • Official Title: Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer Patients With Personalized Therapy (SUBITO) - an International Randomized Phase III Trial

Clinical Trial IDs

  • ORG STUDY ID: M16BRC
  • NCT ID: NCT02810743

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
ddAC-CP-OlaparibddAC-CP-Olaparib
ddAC-mini CTCddAC-mini CTC

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ddAC-CP-OlaparibActive ComparatorddAC; 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.
  • ddAC-CP-Olaparib
ddAC-mini CTCActive ComparatorddAC; 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.
  • ddAC-mini CTC

Eligibility Criteria

        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
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:assessed up to 120 months
Safety Issue:
Description:time from randomization to death from any cause.

Secondary Outcome Measures

Measure:Recurrence free interval
Time Frame:assessed up to 120 months
Safety Issue:
Description:time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first
Measure:Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
Time Frame:up to 30 days after end of treatment
Safety Issue:
Description:Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
Measure:cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Time Frame:assessed up to 120 months
Safety Issue:
Description:cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Measure:Patient reported outcomes
Time Frame:assessed up to 24 months
Safety Issue:
Description:Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires
Measure:cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
Time Frame:assessed up to 120 months
Safety Issue:
Description:cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Netherlands Cancer Institute

Trial Keywords

  • Stage III
  • HER2 negative
  • homologous recombination deficiency (HRD)

Last Updated

June 15, 2021