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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by The Netherlands Cancer Institute
Sponsor:
Information provided by (Responsible Party):
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT01646034
First received: June 14, 2012
Last updated: June 25, 2013
Last verified: June 2013

June 14, 2012
June 25, 2013
July 2012
July 2017   (final data collection date for primary outcome measure)
Event free survival [ Time Frame: assessed up to 120 months ] [ Designated as safety issue: No ]
time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first
Same as current
Complete list of historical versions of study NCT01646034 on ClinicalTrials.gov Archive Site
  • Difference in median overall survival [ Time Frame: assessed up to 120 months ] [ Designated as safety issue: No ]
    time from randomization to death from any cause
  • Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0) [ Time Frame: 6 months after start of treament ] [ Designated as safety issue: Yes ]
    Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)
  • Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0) [ Time Frame: 6 months after start of treatment ] [ Designated as safety issue: Yes ]
    Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)
Same as current
Not Provided
Not Provided
 
High Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer
High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • 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.
  • Drug: chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)
    • chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclofosfamide
    • previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel
    • previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine
  • Experimental: intensified alkylating chemotherapy
    a course chemotherapy with high dose cyclofosfamide, 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.
    Intervention: Drug: carboplatin, thiotepa, and cyclophosphamide
  • Active Comparator: three cycles of chemotherapy

    three cycles of chemotherapy depending on previously received agents

    chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclofosfamide previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine

    Intervention: Drug: chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
86
July 2019
July 2017   (final data collection date for primary outcome measure)

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 in case of score 2 or 3 at immunohistochemistry).
  • The tumor must be ER positive (≥ 10% nuclear staining at IHC) and poorly differentiated (grade 3).

or ER negative; 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.

  • Known BRCA1 or BRCA2 mutation carriers are eligible regardless of the estrogen receptor status of their tumor.
  • 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:

  • 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
Female
18 Years and older
No
Contact: Gabe S Sonke, MD +3120512 ext 2570 g.sonke@nki.nl
Contact: Ingrid AM Mandjes, MSc +3120512 ext 2667 i.mandjes@nki.nl
Netherlands
 
NCT01646034
N12OLG, 2012-000838-19
No
The Netherlands Cancer Institute
The Netherlands Cancer Institute
Not Provided
Principal Investigator: Gabe S Sonke, MD NKI-AVL, Amsterdam
The Netherlands Cancer Institute
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP