Clinical trial NCT01646034: High Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer
Official title: High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: oligo metastatic
HRD deficiency
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
First posted: 2012-07-20
Enrollment: 74
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Event free survival
timeFrame: assessed up to 120 months
Secondary outcomes:
measure: Difference in median overall survival
timeFrame: assessed up to 120 months
measure: Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)
timeFrame: 6 months after start of treament
measure: Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)
timeFrame: 6 months after start of treatment
measure: Difference in quality of life (EORTC QLQ-C30 v 3.0)
timeFrame: 6 and 12 months post treatment
measure: Difference in event free survival
timeFrame: assessed up to 120 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: NKI-AVL
Study officials:
affiliation: NKI-AVL, Amsterdam
name: Gabe S Sonke, MD
role: PRINCIPAL_INVESTIGATOR
References: