Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02810743
Recruitment Status : Recruiting
First Posted : June 23, 2016
Last Update Posted : March 23, 2023
Sponsor:
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: ddAC-CP-Olaparib Drug: ddAC-mini CTC Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 25, 2017
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Olaparib

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: ddAC-CP-Olaparib

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.

 Drug: ddAC-CP-Olaparib
ddAC-CP-Olaparib
Active Comparator: ddAC-mini CTC

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.

 Drug: ddAC-mini CTC
ddAC - mini CTC


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Overall survival [ Time Frame: assessed up to 120 months ]
    time from randomization to death from any cause.


Secondary Outcome Measures :
  1. Recurrence free interval [ Time Frame: assessed up to 120 months ]
    time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first

  2. 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 ]
    Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03

  3. cost-effectiveness measured by costs per quality-adjusted life years (QALYs) [ Time Frame: assessed up to 120 months ]
    cost-effectiveness measured by costs per quality-adjusted life years (QALYs)

  4. Patient reported outcomes [ Time Frame: assessed up to 24 months ]
    Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires

  5. cost-effectiveness measured by incremental cost-effectiveness ratio (ICER) [ Time Frame: assessed up to 120 months ]
    cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02810743


Contacts
Layout table for location contacts
Contact: Sabine Linn, Prof. MD +3120512 ext 9111 s.linn@nki.nl
Contact: Vincent de Jong, MD +3120512 ext 9111 subito@nki.nl

Locations
Layout table for location information
France
Institut Paoli Calmettes Recruiting
Marseille, France, 13009
Contact: A Goncalves, MD         
Principal Investigator: A Goncalves         
Hopital Tenon, University Marie-Curie Not yet recruiting
Paris, France
Contact: J-P Lotz, MD         
Principal Investigator: J-P Lotz, MD         
Netherlands
Medical spectrum Twente Recruiting
Enschede, Overijssel, Netherlands, 7500 KA
Contact: M Wymenga, MD         
Principal Investigator: M Wymenga, MD         
Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Sabine C Linn, MD    +3120512 ext 2951    s.linn@nki.nl   
Contact: Vincent de Jong, MD       subito@nki.nl   
Principal Investigator: Sabine C Linn, MD         
AZVU Recruiting
Amsterdam, Netherlands, 1081 HV
Contact: I Konings, MD       i.konings@vumc.nl   
Principal Investigator: I Konings, MD         
University Medical Center Groningen Recruiting
Groningen, Netherlands
Contact: C Schroder, MD         
Principal Investigator: C Schroder, MD         
LUMC Recruiting
Leiden, Netherlands, 2333 ZA
Contact: J R Kroep, MD       j.r.kroep@lumc.nl   
Principal Investigator: J R Kroep, MD         
Maastricht University Medical Center Recruiting
Maastricht, Netherlands
Contact: V Tjan-Heijnen, MD         
Principal Investigator: V Tjan-Heijnen, MD         
Radboud UMC Recruiting
NIjmegen, Netherlands, 6225GA
Contact: E Kuip, MD         
Principal Investigator: E Kuip, MD         
Erasmus Medical Center Cancer Institute Recruiting
Rotterdam, Netherlands, 3015CE
Contact: A Jager, MD         
Principal Investigator: A Jager, MD         
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584CX
Contact: E van der Wall, MD         
Principal Investigator: E van der Wall, MD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Investigators
Layout table for investigator information
Principal Investigator: Sabine Linn, Prof. MD NKI-AvL
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02810743    
Other Study ID Numbers: M16BRC
First Posted: June 23, 2016    Key Record Dates
Last Update Posted: March 23, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Netherlands Cancer Institute:
Stage III
HER2 negative
homologous recombination deficiency (HRD)
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
 Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents