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

Overview[ - collapse ][ - ]

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.
ConditionBreast Cancer
InterventionDrug: carboplatin, thiotepa, and cyclophosphamide
Drug: chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)
PhasePhase 3
SponsorThe Netherlands Cancer Institute
Responsible PartyThe Netherlands Cancer Institute
ClinicalTrials.gov IdentifierNCT01646034
First ReceivedJune 14, 2012
Last UpdatedJune 25, 2013
Last verifiedJune 2013

Tracking Information[ + expand ][ + ]

First Received DateJune 14, 2012
Last Updated DateJune 25, 2013
Start DateJuly 2012
Estimated Primary Completion DateJuly 2019
Current Primary Outcome MeasuresEvent 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
Current Secondary Outcome Measures
  • 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)

Descriptive Information[ + expand ][ + ]

Brief TitleHigh Dose Chemotherapy in Oligo-metastatic Homologous Recombination Deficient Breast Cancer
Official TitleHigh-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionBreast Cancer
InterventionDrug: 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
Study Arm (s)
  • 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.
  • 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

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment86
Estimated Completion DateJuly 2019
Estimated Primary Completion DateJuly 2017
Eligibility Criteria
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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Gabe S Sonke, MD
+3120512
g.sonke@nki.nl
Location CountriesNetherlands

Administrative Information[ + expand ][ + ]

NCT Number NCT01646034
Other Study ID NumbersN12OLG
Has Data Monitoring CommitteeNo
Information Provided ByThe Netherlands Cancer Institute
Study SponsorThe Netherlands Cancer Institute
CollaboratorsNot Provided
Investigators Principal Investigator: Gabe S Sonke, MD NKI-AVL, Amsterdam
Verification DateJune 2013

Locations[ + expand ][ + ]

NKI-AVL
Amsterdam, Netherlands, 1066 CX
Contact: Gabe S Sonke, MD | +31205122570 | g.sonke@nki.nl
Principal Investigator: Gabe S Sonke, MD
Recruiting