Oligo metastatic breast cancer harboring homologous recombination deficiency and/or the patient has a deleterious germline BRCA1 or BRCA2 mutation MedDRA version: 20.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DOCETAXEL
CAS Number: 114977-28-5
Concentration unit: mg/ml milligram(s)
Sponsors
NKI-AVL
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Histologically or cytologically confirmed infiltrating breast cancer • Oligometastatic disease defined as one to three metastatic lesions, with or without primary tumor, local recurrence, or locoregional lymph node metastases, including the axillary, parasternal, and ipsilateral periclavicular regions. All lesions must be amenable to resection or radiotherapy with curative intent. • 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 • The tumor is deficient in homologous recombination and/or the patient has a deleterious germline BRCA1 or BRCA2 • 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 LVEF =50% measured by echocardiography or MUGA • Signed written informed consent • Able to comply with the protocol Are the trial subjects under 18? no Number of subjects for this age range: 100 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 74 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Malignancy other than breast cancer, unless treated with curative intent and associated with long-term-survival probability >95%,including but not limited to basal cell carcinoma and papillary/follicular thyroid carcinoma. No second breast tumor. • Current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection. • Concurrent anti-cancer treatment or investigational drugs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study will investigates the effect of high dose alkylating chemotherapy compared to standard dose chemotherapy as part of a multimodality approach in patients with oligometastatic HRD positive or BRCA1/2 related breast cancer. ; Secondary Objective: - To study explore the effects of high-dose alkylating chemotherapy in 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 mutated and HRD tumors.;. • HRD based on BRCA1 or BRCA2 mutation and HRD based on BRCA1-like and/or BRCA2-like profile. - To study the difference in toxicity between high-dose alkylating chemotherapy and standard chemotherapy. - To build a biobank of prospectively collected plasma and tumor tissue of cancer patients receiving (high-dose) systemic therapy to study genetic alterations causing resistance to treatment. - To explore predictive value of biomarkers and differences in immune cell population, during and after chemotherapy. - To explore differences in immune cell population and cytokines before and after local treatment of the metastases. ;Primary end point(s): The primary endpoint is the difference in event-free survival (time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first).; Timepoint(s) of evaluation of this end point: Patients will be followed for life. Follow up visits after end of treatment are performed according to local practice | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Difference in median overall survival (time from randomization to death from any cause) • 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) • To build a biobank of prospectively collected plasma and tumor tissue of cancer patients receiving (high-dose) systemic therapy to study genetic alterations causing resistance to treatment. • To explore predictive value of biomarkers and differences in immune cell population, during and after chemotherapy. • To explore differences in immune cell population and cytokines before and after local treatment of the metastases ; Timepoint(s) of evaluation of this end point: At the end of treatment; points 2,3, 4,5,6 At follow up until death; points 1 | — |
Countries
Netherlands
Contacts
Public ContactDr. G.S. Sonke
NKI-AVL
Outcome results
None listed