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
  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.


Condition Intervention Phase
Breast Cancer
Drug: carboplatin, thiotepa, and cyclophosphamide
Drug: chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency

Resource links provided by NLM:


Further study details as provided by The Netherlands Cancer Institute:

Primary Outcome Measures:
  • 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


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)


Estimated Enrollment: 86
Study Start Date: July 2012
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646034

Contacts
Contact: Gabe S Sonke, MD +3120512 ext 2570 g.sonke@nki.nl
Contact: Ingrid AM Mandjes, MSc +3120512 ext 2667 i.mandjes@nki.nl

Locations
Netherlands
NKI-AVL Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Gabe S Sonke, MD    +3120512 ext 2570    g.sonke@nki.nl   
Contact: Ingrid AM Mandjes, MSc    +3120512 ext 2667    i.mandjes@nki.nl   
Principal Investigator: Gabe S Sonke, MD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Investigators
Principal Investigator: Gabe S Sonke, MD NKI-AVL, Amsterdam
  More Information

No publications provided

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT01646034     History of Changes
Other Study ID Numbers: N12OLG, 2012-000838-19
Study First Received: June 14, 2012
Last Updated: June 25, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by The Netherlands Cancer Institute:
oligo metastatic
HRD deficiency

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Thiotepa
Gemcitabine
Docetaxel
Doxorubicin
Carboplatin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 20, 2014