High-dose alkylating chemotherapy in oligo-metastatic breast cancer harboring homologous recombination deficiency

Phase 3

Recruiting

Conditions: breast cancer
mammary neoplasms
10006291

Registration Number: NL-OMON50592

Lead Sponsor: ederlands Kanker Instituut

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 74

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.
•The tumor must be HER2-negative
•The tumor is deficient in homologous recombination and/or the patient has a
deleterious germline BRCA1 or BRCA2 mutation
• 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

Exclusion Criteria

• No prior line of chemotherapy for metastatic disease (a maximum of 3 months
of palliative endocrine therapy is allowed).
• 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.
• Current pregnancy or breastfeeding. Women of childbearing potential must use
adequate contraceptive protection.
• Concurrent anti-cancer treatment or investigational drugs

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is the difference in event-free survival (time from<br /><br>randomization to local recurrence, second primary, distant recurrence or death,<br /><br>whichever comes first).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Difference in median overall survival (time from randomization to death from<br /><br>any cause)<br /><br>• Difference in percentage of patients with grade >2 hematologic toxicity<br /><br>(CTCAE v4.0)<br /><br>• Difference in percentage of patients with grade >2 non-hematologic toxicity<br /><br>(CTCAE v4.0)<br /><br>• Difference in quality of life (EORTC QLQ-C30 v3.0)<br /><br>• To build a biobank of prospectively collected plasma and tumor tissue of<br /><br>cancer patients receiving (high-dose) systemic therapy to study genetic<br /><br>alterations causing resistance to treatment.<br /><br>• To explore predictive value of biomarkers and differences in immune cell<br /><br>population, during and after chemotherapy.<br /><br>• To explore differences in immune cell population and cytokines before and<br /><br>after local treatment of the metastases </p><br>