Breast Cancer
Conditions
Keywords
oligo metastatic, HRD deficiency
Brief 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.
Interventions
DRUGcarboplatin, thiotepa, and cyclophosphamide
tandem intermediate-dose alkylating therapy: carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion.
DRUGchemotherapy (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
Sponsors
The Netherlands Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed infiltrating breast cancer 2. 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. 3. No prior line of chemotherapy for metastatic disease (a maximum of 3 months of palliative endocrine therapy is allowed). 4. 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). 5. The tumor is deficient in homologous recombination and/or the patient has a deleterious germline BRCA1 or BRCA2 mutation. 6. At least stable disease of all tumor lesions after three courses of induction chemotherapy 7. Age ≥18 years 8. World Health Organisation (WHO) performance status 0 or 1 9. Adequate bone marrow function (ANC ≥1.0 x 109/l, platelets ≥100 x 109/l) 10. Adequate hepatic function (ALAT, ASAT and bilirubin ≤2.5 times upper limit of normal) 11. Adequate renal function (creatinine clearance ≥60 ml/min) 12. If clinically recommended echocardiography, MUGA, or MRI to evaluate if LVEF ≥50%; 13. Signed written informed consent 14. Able to comply with the protocol
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival | assessed up to 120 months | time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in median overall survival | assessed up to 120 months | time from randomization to death from any cause |
| Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0) | 6 months after start of treament | Difference in percentage of patients with grade \>2 hematologic toxicity (CTCAE v4.0) |
| Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0) | 6 months after start of treatment | Difference in percentage of patients with grade \>2 non-hematologic toxicity (CTCAE v4.0) |
| Difference in quality of life (EORTC QLQ-C30 v 3.0) | 6 and 12 months post treatment | Difference in quality of life (EORTC QLQ-C30 v 3.0) |
| Difference in event free survival | assessed up to 120 months | o 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. |
Countries
Netherlands
Outcome results
None listed