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

NCT01646034 | Active Not Recruiting Phase 3

• 2 other identifiers: N12OLG2012-000838-19
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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

Keywords

oligo metastatic; HRD deficiency

Outcome Measures

Primary Outcomes (1)

• Event free survival

  time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first

  assessed up to 120 months

Secondary Outcomes (5)

• Difference in median overall survival

  assessed up to 120 months

• 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 non-hematologic toxicity (CTCAE v4.0)

  6 months after start of treatment

• Difference in quality of life (EORTC QLQ-C30 v 3.0)

  6 and 12 months post treatment

• Difference in event free survival

  assessed up to 120 months

Study Arms (2)

intensified alkylating chemotherapy

EXPERIMENTAL

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.

Drug: carboplatin, thiotepa, and cyclophosphamide

three cycles of chemotherapy

ACTIVE COMPARATOR

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

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

Interventions

carboplatin, thiotepa, and cyclophosphamide DRUG

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

intensified alkylating chemotherapy

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

three cycles of chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed infiltrating breast cancer
• 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.
• No prior line of chemotherapy for metastatic disease (a maximum of 3 months of palliative endocrine therapy is allowed).
• 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).
• The tumor is deficient in homologous recombination and/or the patient has a deleterious germline BRCA1 or BRCA2 mutation.
• At least stable disease of all tumor lesions after three courses of induction chemotherapy
• 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)
• If clinically recommended echocardiography, MUGA, or MRI to evaluate if LVEF ≥50%;
• Signed written informed consent
• Able to comply with the protocol

You may not qualify if:

• 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

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

NKI-AVL

Amsterdam, 1066 CX, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 39489924 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Carboplatin; Thiotepa; Cyclophosphamide; Drug Therapy; Docetaxel; Doxorubicin; Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines

Study Officials

• Gabe S Sonke, MD

  NKI-AVL, Amsterdam

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: July 20, 2012
• Study Start: September 1, 2014
• Primary Completion: January 1, 2023
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 12, 2022

Record last verified: 2022-10

Locations

NL (1)