Back to resultsSubstantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer (Subito)
Primary Purpose
Breast Cancer
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ddAC-CP-Olaparib
ddAC-mini CTC
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Stage III, HER2 negative, homologous recombination deficiency (HRD)
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
Sites / Locations
- Institut Paoli CalmettesRecruiting
- Hopital Tenon, University Marie-Curie
- Medical spectrum TwenteRecruiting
- Antoni van LeeuwenhoekRecruiting
- AZVURecruiting
- University Medical Center GroningenRecruiting
- LUMCRecruiting
- Maastricht University Medical CenterRecruiting
- Radboud UMCRecruiting
- Erasmus Medical Center Cancer InstituteRecruiting
- University Medical Center UtrechtRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
ddAC-CP-Olaparib
ddAC-mini CTC
Arm 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.
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.
Outcomes
Primary Outcome Measures
Overall survival
time from randomization to death from any cause.
Secondary Outcome Measures
Recurrence free interval
time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first
Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Patient reported outcomes
Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
Full Information
NCT ID
NCT02810743
First Posted
June 16, 2016
Last Updated
March 21, 2023
Sponsor
The Netherlands Cancer Institute
1. Study Identification
Unique Protocol Identification Number
NCT02810743
Brief Title
Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer
Acronym
Subito
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 25, 2017 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Netherlands Cancer Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Stage III, HER2 negative, homologous recombination deficiency (HRD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
174 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ddAC-CP-Olaparib
Arm Type
Active Comparator
Arm 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.
Arm Title
ddAC-mini CTC
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
ddAC-CP-Olaparib
Intervention Description
ddAC-CP-Olaparib
Intervention Type
Drug
Intervention Name(s)
ddAC-mini CTC
Intervention Description
ddAC - mini CTC
Primary Outcome Measure Information:
Title
Overall survival
Description
time from randomization to death from any cause.
Time Frame
assessed up to 120 months
Secondary Outcome Measure Information:
Title
Recurrence free interval
Description
time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first
Time Frame
assessed up to 120 months
Title
Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
Description
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
Title
cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Description
cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Time Frame
assessed up to 120 months
Title
Patient reported outcomes
Description
Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires
Time Frame
assessed up to 24 months
Title
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
Description
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
Time Frame
assessed up to 120 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sabine Linn, Prof. MD
Phone
+3120512
Ext
9111
Email
s.linn@nki.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Vincent de Jong, MD
Phone
+3120512
Ext
9111
Email
subito@nki.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabine Linn, Prof. MD
Organizational Affiliation
NKI-AvL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A Goncalves, MD
First Name & Middle Initial & Last Name & Degree
A Goncalves
Facility Name
Hopital Tenon, University Marie-Curie
City
Paris
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J-P Lotz, MD
First Name & Middle Initial & Last Name & Degree
J-P Lotz, MD
Facility Name
Medical spectrum Twente
City
Enschede
State/Province
Overijssel
ZIP/Postal Code
7500 KA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M Wymenga, MD
First Name & Middle Initial & Last Name & Degree
M Wymenga, MD
Facility Name
Antoni van Leeuwenhoek
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sabine C Linn, MD
Phone
+3120512
Ext
2951
Email
s.linn@nki.nl
First Name & Middle Initial & Last Name & Degree
Vincent de Jong, MD
Email
subito@nki.nl
First Name & Middle Initial & Last Name & Degree
Sabine C Linn, MD
Facility Name
AZVU
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
I Konings, MD
Email
i.konings@vumc.nl
First Name & Middle Initial & Last Name & Degree
I Konings, MD
Facility Name
University Medical Center Groningen
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C Schroder, MD
First Name & Middle Initial & Last Name & Degree
C Schroder, MD
Facility Name
LUMC
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J R Kroep, MD
Email
j.r.kroep@lumc.nl
First Name & Middle Initial & Last Name & Degree
J R Kroep, MD
Facility Name
Maastricht University Medical Center
City
Maastricht
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
V Tjan-Heijnen, MD
First Name & Middle Initial & Last Name & Degree
V Tjan-Heijnen, MD
Facility Name
Radboud UMC
City
NIjmegen
ZIP/Postal Code
6225GA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
E Kuip, MD
First Name & Middle Initial & Last Name & Degree
E Kuip, MD
Facility Name
Erasmus Medical Center Cancer Institute
City
Rotterdam
ZIP/Postal Code
3015CE
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A Jager, MD
First Name & Middle Initial & Last Name & Degree
A Jager, MD
Facility Name
University Medical Center Utrecht
City
Utrecht
ZIP/Postal Code
3584CX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
E van der Wall, MD
First Name & Middle Initial & Last Name & Degree
E van der Wall, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer
We'll reach out to this number within 24 hrs