Breast CancerPhase 3SubitoNCT02810743
Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer
A Phase 3 study testing ddAC-CP-Olaparib and ddAC-mini CTC in people with Breast Cancer, run by The Netherlands Cancer Institute at 11 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- ddAC-CP-Olaparib and ddAC-mini CTC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 174 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 25 Jan 2017to 1 Dec 2033
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
Netherlands9 sites
Antoni van Leeuwenhoek
Amsterdam, 1066 CX
AZVU
Amsterdam, 1081 HV
Medical spectrum Twente
Enschede, Overijssel, 7500 KA
University Medical Center Groningen
Groningen
LUMC
Leiden, 2333 ZA
Maastricht University Medical Center
Maastricht
Radboud UMC
Nijmegen, 6225GA
Erasmus Medical Center Cancer Institute
Rotterdam, 3015CE
University Medical Center Utrecht
Utrecht, 3584CX
France2 sites
Institut Paoli Calmettes
Marseille, 13009
Hopital Tenon, University Marie-Curie
Paris
About this study
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
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.
- Conditions
- Breast Cancer
- Being tested
- ddAC-CP-Olaparib, ddAC-mini CTC
- Keywords
- Stage III, HER2 negative, homologous recombination deficiency (HRD)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ddAC-CP-OlaparibDrug
ddAC-CP-Olaparib
ddAC-mini CTCDrug
ddAC - mini CTC
| Study group | Role | What they receive |
|---|---|---|
| ddAC-CP-Olaparib | Active comparator | 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. Receives: Drug: ddAC-CP-Olaparib |
| ddAC-mini CTC | Active comparator | 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. Receives: Drug: ddAC-mini CTC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival in all patients
time from randomization to death from any cause in all patients
Measured: assessed up to 120 months
Secondary outcomes (7)
Overall survival in patients without a germline BRCA1/2 mutation
time from randomization to death from any cause in without a germline BRCA1/2 mutation
Measured: assessed up to 120 months
Recurrence free interval in all patients
time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first in all patients
Measured: assessed up to 120 months
Recurrence free interval in patients with an HR impaired tumor
time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first in patients with an HR impaired tumor
Measured: assessed up to 120 months
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
Measured: up to 30 days after end of treatment
cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Measured: assessed up to 120 months
Patient reported outcomes
Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires
Measured: assessed up to 24 months
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
Measured: assessed up to 120 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2016 (estimated)
- Study start25 Jan 2017
- Primary completion18 Jul 2024
- Study completion1 Dec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 174 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sabine Linn, Prof. MD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02810743
- Sponsor's protocol ID
- M16BRC
- Acronym
- Subito
- Status last verified
- May 2026
- First submitted
- 16 Jun 2016
- Last updated
- 1 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Seefat RL, Vliek SB, de Jong VMT, Balduzzi S, Mandjes IA, Retel VP, Eekhout I, Delfos M, Schot M, Holtkamp MJ, van Rosmalen MM, Leeneman B, Blommestein H, Huitema ADR, Rosenberg EH, Nederlof PM, Chan TWS, van Rhenen A, Wondergem MJ, Schaap NPM, Snijders TJF, Van der Poel MWM, Plattel WJ, van Werkhoven E, van Tinteren H, Smidt ML, Wesseling J, Jonkers J, Rottenberg S, Vrancken Peeters MTFD, Voermans C, Maduro JH, Kroep JR, Schroder CP, Kuip EJM, Goncalves A, Nuver J, Wymenga ANM, Bijlsma RM, van der Wall E, Konings IRHM, Tjan-Heijnen VCG, Jongen-Lavrencic M, Jager A, Linn SC. Targeting homologous recombination deficiency with intensified chemotherapy versus standard chemotherapy followed by olaparib in stage III breast cancer (SUBITO): an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2026 Jul;27(7):795-807. doi: 10.1016/S1470-2045(26)00131-2.
PubMed 42372741
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02810743
- Acronym / sponsor ID
- Subito / M16BRC
- Conditions
- Breast Cancer
- Keywords
- Stage III, HER2 negative, homologous recombination deficiency (HRD)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 174 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- 25 Jan 2017 (actual)
- Primary completion
- 18 Jul 2024 (actual)
- Study completion
- 1 Dec 2033 (estimated)
- First posted
- 23 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ddAC-CP-Olaparib | Active comparator | Drug: ddAC-CP-OlaparibddAC; 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-mini CTC | Active comparator | Drug: ddAC-mini CTCddAC; 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ddAC-CP-OlaparibddAC-CP-Olaparib | Drug | ddAC-CP-Olaparib |
| ddAC-mini CTCddAC - mini CTC | Drug | ddAC-mini CTC |
Primary outcome
Overall survival in all patients
Time frame: assessed up to 120 months
time from randomization to death from any cause in all patients
7 secondary outcomes
Overall survival in patients without a germline BRCA1/2 mutation
Time frame: assessed up to 120 months
Recurrence free interval in all patients
Time frame: assessed up to 120 months
Recurrence free interval in patients with an HR impaired tumor
Time frame: assessed up to 120 months
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
cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Time frame: assessed up to 120 months
Patient reported outcomes
Time frame: assessed up to 24 months
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
Time frame: assessed up to 120 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
- Derived from this study: PubMed 42372741Seefat RL, Vliek SB, de Jong VMT, Balduzzi S, Mandjes IA, Retel VP, Eekhout I, Delfos M, Schot M, Holtkamp MJ, van Rosmalen MM, Leeneman B, Blommestein H, Huitema ADR, Rosenberg EH, Nederlof PM, Chan TWS, van Rhenen A, Wondergem MJ, Schaap NPM, Snijders TJF, Van der Poel MWM, Plattel WJ, van Werkhoven E, van Tinteren H, Smidt ML, Wesseling J, Jonkers J, Rottenberg S, Vrancken Peeters MTFD, Voermans C, Maduro JH, Kroep JR, Schroder CP, Kuip EJM, Goncalves A, Nuver J, Wymenga ANM, Bijlsma RM, van der Wall E, Konings IRHM, Tjan-Heijnen VCG, Jongen-Lavrencic M, Jager A, Linn SC. Targeting homologous recombination deficiency with intensified chemotherapy versus standard chemotherapy followed by olaparib in stage III breast cancer (SUBITO): an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2026 Jul;27(7):795-807. doi: 10.1016/S1470-2045(26)00131-2.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sabine Linn, Prof. MD principal investigator
The Netherlands Cancer Institute
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ddAC-CP-Olaparib and ddAC-mini CTC in people with Breast Cancer, run by The Netherlands Cancer Institute at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Netherlands, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival in all patients (time frame: assessed up to 120 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02810743, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.