Study of Cabazitaxel in Patients With Metastatic Breast Cancer Previously Treated With Taxanes

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Hellenic Cooperative Oncology Group
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Hellenic Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01693549
First received: September 20, 2012
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to determine whether cabazitaxel is effective in the treatment of metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Cabazitaxel
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Cabazitaxel as 2nd Line Treatment in Patients With HER-2 Negative Metastatic Breast Cancer Previously Treated With Taxanes

Resource links provided by NLM:


Further study details as provided by Hellenic Cooperative Oncology Group:

Primary Outcome Measures:
  • Objective response rate (ORR). [ Time Frame: At an average of 24 months for each patient ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response. [ Time Frame: From the time measurement criteria are first met for partial or complete response until the first date of documented progressive disease or death from any cause without prior documentation of progression assessed up to 30 months. ] [ Designated as safety issue: No ]
  • Evaluation of progression-free survival (PFS) [ Time Frame: From study entry until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression, assessed up to 30 months. ] [ Designated as safety issue: No ]
  • Evaluation of overall survival (OS) [ Time Frame: Defined as the time in months from study entry until the time of death, assessed up to 30 months. ] [ Designated as safety issue: No ]
  • Assessment of safety and tolerability. [ Time Frame: Evaluation of Adverse Events will be performed every 21 days (per cycle) during treatment assessed up to 30 months. ] [ Designated as safety issue: Yes ]
    Distribution of adverse events according to severity grade.

  • Value of prognostic and/or predictive biomarkers measured in tissue and blood samples [ Time Frame: Tumor blocks and blood DNA will be collected at study entry and plasma at study entry, on week 3 and week 6 of treatment. ] [ Designated as safety issue: No ]

    βΙ,βΙΙ,βΙΙΙ,βIVb, βV-tubulin isotypes,HIF1α,microtubule-associated proteins such as Tau,MAP2,MAP4 & microtubule-sequestering proteins such as stathmin, will be assessed. Moreover, evaluation of p53,BCL2,BIM,γ-actin,LIMK2, TGFBI,Aurora-A,as well as the expression of the enzyme CYP3A and multidrug transporters such as P-glycoprotein. The abovementioned factors will be assessed by immunohistochemistry at the protein level and by quantitative real-time PCR at the RNA level.

    Also, given the clinical significance of the anti-angiogenic effects of cytotoxic chemotherapy,we will investigate the effect of treatment on surrogate biomarkers of angiogenesis, such as VEGF-A as well as the effect of chemotherapy on kinetics of soluble biomarkers,using ELISA.

    In addition,genetic polymorphisms in drug-metabolizing enzymes and drug transporters, such as the CYP3A and ABCB1 genes, will be explored in blood DNA and their association with the toxicity and efficacy of cabazitaxel will be assessed.



Estimated Enrollment: 84
Study Start Date: September 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabazitaxel
Cabazitaxel(XRP6258) will be administered on day 1 of each cycle, every 21 days, at a dose of 25 mg/m² by i.v. route in 1 hour. Treatment can be continued until patient's consent withdrawal, intolerable toxicity or documented disease progression.
Drug: Cabazitaxel
Other Names:
  • Jevtana
  • XRP6258

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Female patients aged 18 to 75 years
  • Patients must have received 1st-line chemotherapy for locally recurrent / metastatic disease
  • Prior taxane-containing treatment (paclitaxel, docetaxel or nab-paclitaxel), either for advanced disease or as neoadjuvant/adjuvant chemotherapy. In case of early relapse (relapse during neoadjuvant/adjuvant chemotherapy or disease-free interval less than 6 months), neoadjuvant/adjuvant chemotherapy will be considered as 1st-line treatment
  • Diagnosis of HER-2 negative (HER-2 <2+ by immunohistochemistry and/or FISH or CISH negative) metastatic breast adenocarcinoma confirmed by the pathology department of the enrolling institution
  • Eastern Cooperative Oncology Group performance status (PS) of 0-1
  • Life expectancy of at least 12 weeks
  • Measurable disease by the Response Criteria in Solid Tumors 1.1 (RECIST 1.1) method (at least one measurable lesion)
  • Laboratory values within the specified ranges within 1 week of study enrolment:

    1. Hemoglobin ≥ 9.0 g/dL
    2. Absolute neutrophil count of ≥ 1.5 x 10^9/L
    3. Thrombocyte count of ≥ 100 x 10^9/L
    4. Serum creatinine ≤ 1.5 upper limit of normal (ULN). If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded
    5. SGOT (AST), SGPT (ALT) ≤ 2.5 x ULN and alkaline phosphatase ≤ 2.5 x ULN, total bilirubin ≤ ULN (the same limits also refer to patients with liver metastases)
  • Previous treatment for loco-regional disease is allowed, including surgical procedures or palliative radiotherapy (such treatments must have been completed at least 4 weeks before enrolment)
  • Compliance of the patient regarding scheduled visits, treatment plan, laboratory tests and other procedures of the study.
  • The enrolment of patients with controlled brain metastases is allowed (metastases that have been treated with radiotherapy and remained stable for at least 4 weeks following the completion of radiation treatment)

Exclusion Criteria:

  • Patients that have received more than one lines of chemotherapy for locally recurrent/metastatic disease
  • Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a wash-out period of two weeks is necessary for patients who are already on these treatments)
  • Patients with CTC grade 2 or greater neuropathy at baseline
  • Diagnosis of spinal cord compression or carcinomatous meningitis
  • Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
  • Patients with clinically significant cardiac disease (e.g. congestive heart failure, unstable angina, myocardial infarction) within 6 months from study entry
  • Any other significant acute or chronic medical or psychiatric condition or abnormal laboratory finding which, according to the investigator's opinion, could result in excessive danger, regarding the participation of the patient in the study.
  • Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocol
  • Any concurrent active malignancy other than non-melanoma skin cancer or in situ carcinoma of the cervix
  • Concurrent administration of other investigational treatments and/or anti-neoplastic agents
  • Pregnancy or lactation. Patients should be surgically sterile or post-menopausal or they must agree to use adequate contraceptive methods during study period. For all patients of childbearing potential a serum or urine pregnancy test is needed. The definition of effective contraceptive methods will be based on the investigator's opinion.
  • History of severe hypersensitivity reaction (≥grade 3) to docetaxel or polysorbate 80 containing 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: NCT01693549

Contacts
Contact: Angelos Koutras, MD 0030 261 0 999810 angkoutr@otenet.gr

Locations
Greece
Division of Oncology, 2nd Dept of Internal Medicine, Propaedeutic, University Hospital "Attikon" Recruiting
Athens, Greece, 12462
Contact: Diamanto Psyrri, MD       psyrri237@yahoo.gr   
Principal Investigator: Diamanto Psyrri, MD         
Oncology section, Dept of Clinical Therapeutics, General Hospital of Athens "Alexandra" Recruiting
Athens, Greece, 11528
Contact: Christos Papadimitriou, Ass.Prof       chr_papadim@yahoo.gr   
Principal Investigator: Christos Papadimitriou, Ass.Prof         
1st Dept of Medical Oncology, Metropolitan Hospital Recruiting
Athens, Greece, 18547
Contact: Dimitrios Bafaloukos, MD       dimmp@otenet.gr   
Principal Investigator: Dimitrios Bafaloukos, MD         
2nd Dept of Medical Oncology, General Hospital of Athens "Hippokratio" Recruiting
Athens, Greece, 11527
Contact: Dimitrios Pectasides, Professor       pectasid@otenet.gr   
Principal Investigator: Dimitrios Pectasides, Professor         
Dept of Medical Oncology, 251 General Air Force Hospital Recruiting
Athens, Greece, 11525
Contact: Nikolaos Kentepozidis, MD       kentenik@hotmail.com   
Principal Investigator: Nikolaos Kentepozidis, MD         
3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital Recruiting
Athens, Greece, 14564
Contact: Eleni Res, MD       hecogaga@otenet.gr   
Principal Investigator: Eleni Res, MD         
2nd Dept of Medical Oncology, Metropolitan Hospital Recruiting
Athens, Greece, 18547
Contact: Christos Christodoulou, MD       c_christodoulou@yahoo.gr   
Principal Investigator: Christos Christodoulou, MD         
2nd Dept of Medical Oncology, Agios Savvas Cancer Hospital Recruiting
Athens, Greece
Contact: Christos Panopoulos, MD       smart12@otenet.gr   
Principal Investigator: Christos Panopoulos, MD         
3rd Dept of Medical Oncology, Hygeia Hospital Recruiting
Athens, Greece, 15123
Contact: Evangelia Razis, MD       e.razis@hygeia.gr   
Principal Investigator: Evangelia Razis, MD         
Oncology Dept., General Hospital of Chania "Agios Georgios" Recruiting
Chania, Greece, 73300
Contact: Ioannis Varthalitis, MD       oncol@chaniahospital.gr   
Principal Investigator: Ioannis Varthalitis, MD         
Dept of Medical Oncology, University Hospital of Heraklion Recruiting
Heraklio, Greece, 71110
Contact: Vassilios Georgoulias, Professor       georgoul@med.uoc.gr   
Principal Investigator: Vassilios Georgoulias, Professor         
Dept of Medical Oncology, Ioannina University Hospital Recruiting
Ioannina, Greece, 45110
Contact: George Pentheroudakis, MD       gpenther@otenet.gr   
Principal Investigator: George Pentheroudakis, Ass.Prof         
Dept of Medical Oncology, Larissa University Hospital Recruiting
Larissa, Greece, 41334
Contact: Christos Papandreou, Ass.Prof       cpapandreou@med.uth.gr   
Principal Investigator: Christos Papandreou, Ass.Prof         
Division of Oncology, Dept of Internal Medicine, University Hospital of Patras Recruiting
Rio, Patras, Greece, 26504
Contact: Angelos Koutras       angkoutr@otenet.gr   
Principal Investigator: Angelos Koutras, MD         
Dept of Medical Oncology, Papageorgiou General Hospital Recruiting
Thessaloniki, Greece, 56429
Contact: George Fountzilas, Professor       gfountzil@auth.gr   
Principal Investigator: George Fountzilas, Professor         
Sponsors and Collaborators
Hellenic Cooperative Oncology Group
Sanofi
Investigators
Study Chair: Angelos Koutras, MD Division of Oncology,Dept of Internal Medicine,University Hospital of Patras
  More Information

No publications provided

Responsible Party: Hellenic Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01693549     History of Changes
Other Study ID Numbers: HE 11B/11, 2011-003625-97
Study First Received: September 20, 2012
Last Updated: July 17, 2014
Health Authority: Greece: National Organization of Medicines
Greece: Ethics Committee

Keywords provided by Hellenic Cooperative Oncology Group:
HER-2 negative
Metastatic breast adenocarcinoma

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 28, 2014