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

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ClinicalTrials.gov Identifier: NCT01646034
Recruitment Status : Recruiting
First Posted : July 20, 2012
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
The Netherlands Cancer Institute

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.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency
Study Start Date : September 2014
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: intensified alkylating chemotherapy
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
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 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)
  • 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




Primary Outcome Measures :
  1. Event free survival [ Time Frame: assessed up to 120 months ]
    time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first


Secondary Outcome Measures :
  1. Difference in median overall survival [ Time Frame: assessed up to 120 months ]
    time from randomization to death from any cause

  2. Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0) [ Time Frame: 6 months after start of treament ]
    Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)

  3. Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0) [ Time Frame: 6 months after start of treatment ]
    Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)

  4. Difference in quality of life (EORTC QLQ-C30 v 3.0) [ Time Frame: 6 and 12 months post treatment ]
    Difference in quality of life (EORTC QLQ-C30 v 3.0)

  5. Difference in event free survival [ Time Frame: assessed up to 120 months ]

    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01646034


Contacts
Contact: Gabe S Sonke, MD +3120512 ext 2570 g.sonke@nki.nl
Contact: Tessa Steenbruggen, MD +3120512 ext 9111 t.steenbruggen@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 2880    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

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT01646034     History of Changes
Other Study ID Numbers: N12OLG
2012-000838-19 ( EudraCT Number )
First Posted: July 20, 2012    Key Record Dates
Last Update Posted: July 2, 2018
Last Verified: June 2018

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
Paclitaxel
Docetaxel
Gemcitabine
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Doxorubicin
Thiotepa
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating