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

NCT ID: NCT01646034

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2026-10-31

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intensified alkylating chemotherapy

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.

Group Type: EXPERIMENTAL

carboplatin, thiotepa, and cyclophosphamide

Intervention Type: DRUG

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

three cycles of chemotherapy

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

Group Type: ACTIVE_COMPARATOR

chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)

Intervention Type: DRUG

• 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

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gabe S Sonke, MD

Role: PRINCIPAL_INVESTIGATOR

NKI-AVL, Amsterdam

Locations

NKI-AVL

Amsterdam, , Netherlands

Countries

Netherlands

References

van Ommen-Nijhof A, Steenbruggen TG, Wiersma TG, Balduzzi S, Daletzakis A, Holtkamp MJ, Delfos M, Schot M, Beelen K, Siemerink EJM, Heijns J, Mandjes IA, Wesseling J, Rosenberg EH, Vrancken Peeters MJT, Linn SC, Sonke GS. Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study. Eur J Cancer. 2024 Dec;213:115083. doi: 10.1016/j.ejca.2024.115083. Epub 2024 Oct 20.

Reference Type: DERIVED

PMID: 39489924 (View on PubMed)

Other Identifiers

2012-000838-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

N12OLG

Identifier Type: -

Identifier Source: org_study_id