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

Phase 2

Withdrawn

• Conditions: breast cancer; mammary neoplasms; 10006291

• Registration Number: NL-OMON36155
• Lead Sponsor: ederlands Kanker Instituut

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 100

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. Staging examinations must have included a PET-scan plus diagnostic CT-scan of the chest and abdomen, and an isotope bone scan. When the isotope bone scan is doubtful and plain radiographs do not explain the abnormality, MRI or CT-scan of the affected skeletal region must be performed.
- The tumor must be HER2-negative (either score 0 or 1 at immunohistochemistry or negative at in situ hybridization [CISH or FISH] in case of score 2 or 3 at immunohistochemistry).
- The tumor must be ER and PgR negative (<10% nuclear staining at IHC) unless the patient is a known BRCA1 or BRCA2 mutation carrier. The rare tumors that are ER-negative and PgR-positive will be eligible, if this pattern of hormone receptor expression can be verified in the NKI-AVL reference pathology lab.
- 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)
- LVEF *50% measured by echocardiography or MUGA
- Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Signed written informed consent
- Able to comply with the protocol

Exclusion Criteria

- Malignancy other than breast cancer, unless treated with curative intent without the use of chemotherapy or radiation therapy
- 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 three-year progression-free survival after start of<br /><br>treatment</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints are:<br /><br>* Difference in three-year progression-free survival between high-dose<br /><br>alkylating chemotherapy compared with standard chemotherapy in patients whose<br /><br>tumor harbors HRD<br /><br>* Difference in percentage of patients with complete remission after high-dose<br /><br>alkylating chemotherapy compared with standard chemotherapy in patients whose<br /><br>tumor harbors HRD<br /><br>* Difference in median progression-free survival between the two treatment arms<br /><br>* Difference in median overall survival (time from start of treatment to death<br /><br>from any cause)<br /><br>* Difference in three-year progression-free survival between patients with and<br /><br>without HRD<br /><br>* Difference in percentage of patients with grade >2 hematological toxicity<br /><br>(CTCAE v4.0)<br /><br>* Difference in percentage of patients with grade >2 non-hematological toxicity<br /><br>(CTCAE v4.0)</p><br>