Breast CancerPhase 3OligoNCT01646034
High Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer
A Phase 3 study testing carboplatin, thiotepa, and cyclophosphamide and chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine) in people with Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
This study investigates the effect of high-dose alkylating chemotherapy compared with standard chemotherapy as part of a multimodality treatment approach in patients with oligo-metastatic breast cancer harboring homologous recombination deficiency. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- carboplatin, thiotepa, and cyclophosphamide and chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2014to Oct 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed infiltrating breast cancer
- Oligometastatic disease defined as one to three distant metastatic lesions, with or without primary tumor, local recurrence, or locoregional lymph node metastases, including the ipsilateral axillary, parasternal, and periclavicular regions. All lesions must be amenable to resection or radiotherapy with curative intent. Staging examinations must have included a PET-CT-scan and a MRI of the liver in case of liver metastases. Clustered lymph nodes that can be irradiated with curative intent in a single field are defined as a single lesion. Histologic or cytologic confirmation of at least one distant metastatic lesion is required.
- No prior line of chemotherapy for metastatic disease (a maximum of 3 months of palliative endocrine therapy is allowed).
- The tumor must be HER2-negative (either score 0 or 1 at immunohistochemistry or negative at in situ hybridization in case of score 2 or 3 at immunohistochemistry).
- The tumor is deficient in homologous recombination and/or the patient has a deleterious germline BRCA1 or BRCA2 mutation.
- At least stable disease of all tumor lesions after three courses of induction chemotherapy
Show all 14Show fewer
- Age ≥18 years
- World Health Organisation (WHO) performance status 0 or 1
- Adequate bone marrow function (ANC ≥1.0 x 109/l, platelets ≥100 x 109/l)
- Adequate hepatic function (ALAT, ASAT and bilirubin ≤2.5 times upper limit of normal)
- Adequate renal function (creatinine clearance ≥60 ml/min)
- If clinically recommended echocardiography, MUGA, or MRI to evaluate if LVEF ≥50%;
- Signed written informed consent
- Able to comply with the protocol
Who cannot join
- No malignancy other than breast cancer, unless treated with curative intent without the use of chemotherapy or radiation therapy
- No current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection.
- No concurrent anti-cancer treatment or investigational drugs
Trial locations and contacts
1 site in 1 country.
About this study
Official title: High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency
This study investigates the effect of high-dose alkylating chemotherapy compared with standard chemotherapy as part of a multimodality treatment approach in patients with oligo-metastatic breast cancer harboring homologous recombination deficiency.
- Conditions
- Breast Cancer
- Being tested
- carboplatin, thiotepa, and cyclophosphamide, chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)
- Keywords
- oligo metastatic, HRD deficiency
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carboplatin, thiotepa, and cyclophosphamideDrug
tandem intermediate-dose alkylating therapy: carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion.
chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)Drug
- chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclofosfamide
- chemotherapy naïve;1 cycle of dose-dense Adriamycin and cyclophosphamide followed by 4 cycles of carboplatin and paclitaxel
- previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel
- previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine
| Study group | Role | What they receive |
|---|---|---|
| intensified alkylating chemotherapy | Experimental | a course chemotherapy with high dose cyclophosphamide, G-CSF and peripheral blood progenitor cell (PBPC) harvest followed by tandem intermediate-dose alkylating therapy (miniCTC, carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion. Receives: Drug: carboplatin, thiotepa, and cyclophosphamide |
| three cycles of chemotherapy | Active comparator | three cycles of chemotherapy depending on previously received agents
chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclophosphamide previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine Receives: Drug: chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event free survival
time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first
Measured: assessed up to 120 months
Secondary outcomes (5)
Difference in median overall survival
time from randomization to death from any cause
Measured: assessed up to 120 months
Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)
Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)
Measured: 6 months after start of treament
Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)
Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)
Measured: 6 months after start of treatment
Difference in quality of life (EORTC QLQ-C30 v 3.0)
Difference in quality of life (EORTC QLQ-C30 v 3.0)
Measured: 6 and 12 months post treatment
Difference in event free survival
- Difference in event free survival in the subgroups based on:
- Estrogen receptor status;
- Origin of the oligo-metastatic lesion (lymphnodes versus bone versus visceral metastases);
- Primary or recurrent oligometastatic breast cancer;
- BRCA1 mutation/profile or BRCA2 mutation/profile;
- HRD based on BRCA1 or BRCA2 mutation and HRD based on BRCA1-like and/or BRCA2-like profile.
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 posted20 Jul 2012 (estimated)
- Study startSep 2014
- Primary completionJan 2023 (estimated)
- Study completionOct 2026 (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
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gabe S Sonke, MD, Principal investigator, NKI-AVL, Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01646034
- Sponsor's protocol ID
- N12OLG
- Other IDs
- 2012-000838-19
- Acronym
- Oligo
- Status last verified
- Oct 2022
- First submitted
- 14 Jun 2012
- Last updated
- 12 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
van Ommen-Nijhof A, Steenbruggen TG, Wiersma TG, Balduzzi S, Daletzakis A, Holtkamp MJ, Delfos M, Schot M, Beelen K, Siemerink EJM, Heijns J, Mandjes IA, Wesseling J, Rosenberg EH, Vrancken Peeters MJT, Linn SC, Sonke GS. Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study. Eur J Cancer. 2024 Dec;213:115083. doi: 10.1016/j.ejca.2024.115083. Epub 2024 Oct 20.
PubMed 39489924
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency
- ClinicalTrials.gov ID
- NCT01646034
- Acronym / sponsor ID
- Oligo / N12OLG
- Conditions
- Breast Cancer
- Keywords
- oligo metastatic, HRD deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 74 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Jan 2023 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 20 Jul 2012 (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.
This study investigates the effect of high-dose alkylating chemotherapy compared with standard chemotherapy as part of a multimodality treatment approach in patients with oligo-metastatic breast cancer harboring homologous recombination deficiency.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intensified alkylating chemotherapy | Experimental | Drug: carboplatin, thiotepa, and cyclophosphamidea course chemotherapy with high dose cyclophosphamide, G-CSF and peripheral blood progenitor cell (PBPC) harvest followed by tandem intermediate-dose alkylating therapy (miniCTC, carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion. |
| three cycles of chemotherapy | Active comparator | Drug: chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)three cycles of chemotherapy depending on previously received agents chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclophosphamide previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically or cytologically confirmed infiltrating breast cancer
- Oligometastatic disease defined as one to three distant metastatic lesions, with or without primary tumor, local recurrence, or locoregional lymph node metastases, including the ipsilateral axillary, parasternal, and periclavicular regions. All lesions must be amenable to resection or radiotherapy with curative intent. Staging examinations must have included a PET-CT-scan and a MRI of the liver in case of liver metastases. Clustered lymph nodes that can be irradiated with curative intent in a single field are defined as a single lesion. Histologic or cytologic confirmation of at least one distant metastatic lesion is required.
- No prior line of chemotherapy for metastatic disease (a maximum of 3 months of palliative endocrine therapy is allowed).
- The tumor must be HER2-negative (either score 0 or 1 at immunohistochemistry or negative at in situ hybridization in case of score 2 or 3 at immunohistochemistry).
- The tumor is deficient in homologous recombination and/or the patient has a deleterious germline BRCA1 or BRCA2 mutation.
Key exclusion criteria (3 listed)
- No malignancy other than breast cancer, unless treated with curative intent without the use of chemotherapy or radiation therapy
- No current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection.
- No concurrent anti-cancer treatment or investigational drugs
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 |
|---|---|---|
| carboplatin, thiotepa, and cyclophosphamidetandem intermediate-dose alkylating therapy: carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion. | Drug | intensified alkylating chemotherapy |
| chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)* chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclofosfamide * chemotherapy naïve;1 cycle of dose-dense Adriamycin and cyclophosphamide followed by 4 cycles of carboplatin and paclitaxel * previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel * previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine | Drug | three cycles of chemotherapy |
Primary outcome
Event free survival
Time frame: assessed up to 120 months
time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first
5 secondary outcomes
Difference in median overall survival
Time frame: assessed up to 120 months
Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)
Time frame: 6 months after start of treament
Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)
Time frame: 6 months after start of treatment
Difference in quality of life (EORTC QLQ-C30 v 3.0)
Time frame: 6 and 12 months post treatment
Difference in event free survival
Time frame: assessed up to 120 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2022.
- Derived from this study: PubMed 39489924van Ommen-Nijhof A, Steenbruggen TG, Wiersma TG, Balduzzi S, Daletzakis A, Holtkamp MJ, Delfos M, Schot M, Beelen K, Siemerink EJM, Heijns J, Mandjes IA, Wesseling J, Rosenberg EH, Vrancken Peeters MJT, Linn SC, Sonke GS. Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study. Eur J Cancer. 2024 Dec;213:115083. doi: 10.1016/j.ejca.2024.115083. Epub 2024 Oct 20.
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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.
Gabe S Sonke, MD principal investigator
NKI-AVL, Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing carboplatin, thiotepa, and cyclophosphamide and chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine) in people with Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
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 14 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
Results are not available in the source record.
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?
Event free survival (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 NCT01646034, 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 12 Oct 2022.