Clinical Trials /

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

NCT01646034

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: High Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer
  • Official Title: High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency

Clinical Trial IDs

  • ORG STUDY ID: N12OLG
  • SECONDARY ID: 2012-000838-19
  • NCT ID: NCT01646034

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
carboplatin, thiotepa, and cyclophosphamideintensified alkylating chemotherapy
chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)three cycles of chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
intensified alkylating chemotherapyExperimentala 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.
  • carboplatin, thiotepa, and cyclophosphamide
three cycles of chemotherapyActive Comparatorthree 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
  • chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event free survival
Time Frame:assessed up to 120 months
Safety Issue:
Description:time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first

Secondary Outcome Measures

Measure:Difference in median overall survival
Time Frame:assessed up to 120 months
Safety Issue:
Description:time from randomization to death from any cause
Measure:Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)
Time Frame:6 months after start of treament
Safety Issue:
Description:Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)
Measure:Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)
Time Frame:6 months after start of treatment
Safety Issue:
Description:Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)
Measure:Difference in quality of life (EORTC QLQ-C30 v 3.0)
Time Frame:6 and 12 months post treatment
Safety Issue:
Description:Difference in quality of life (EORTC QLQ-C30 v 3.0)
Measure:Difference in event free survival
Time Frame:assessed up to 120 months
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Netherlands Cancer Institute

Trial Keywords

  • oligo metastatic
  • HRD deficiency

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