High Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer

Phase 3

Active, not recruiting

• Conditions: Breast Cancer
• Interventions: Drug: carboplatin, thiotepa, and cyclophosphamide; Drug: chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)

• Registration Number: NCT01646034
• Lead Sponsor: The Netherlands Cancer Institute

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-06-14
• Study First Submitted QC: 2012-07-19
• Study First Posted: 2012-07-20
• Study Start: 2014-09
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-11
• Last Update Posted: 2022-10-12
• Primary Completion: 2023-01
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 74

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
intensified alkylating chemotherapy	carboplatin, thiotepa, and cyclophosphamide	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.
three cycles of chemotherapy	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

Primary Outcome Measures

Name	Time	Method
Event free survival	assessed up to 120 months	time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first

Secondary Outcome Measures

Name	Time	Method
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 median overall survival	assessed up to 120 months	time from randomization to death from any cause
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.
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)

Trial Locations

Locations (1)

NKI-AVL; 🇳🇱 Amsterdam, Netherlands