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

Breast Cancer Clinical Trial

— Oligo  

Official title:

High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01646034
• Other study ID #: N12OLG
• Secondary ID: 2012-000838-19
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 2014
• Est. completion date: October 2026

Study information

• Verified date: October 2022
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 74
• Est. completion date: October 2026
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• carboplatin, thiotepa, and cyclophosphamide
tandem intermediate-dose alkylating therapy: carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion.
• chemotherapy (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

Locations

Country	Name	City	State
Netherlands	NKI-AVL	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival	time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first	assessed up to 120 months
Secondary	Difference in median overall survival	time from randomization to death from any cause	assessed up to 120 months
Secondary	Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)	Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)	6 months after start of treament
Secondary	Difference in percentage of patients with grade >2 non-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
Secondary	Difference in quality of life (EORTC QLQ-C30 v 3.0)	Difference in quality of life (EORTC QLQ-C30 v 3.0)	6 and 12 months post treatment
Secondary	Difference in event free survival	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.	assessed up to 120 months