Early Cardiac Toxicity of Adjuvant CT in Elderly BC.

This study has been terminated.
(Slow recruitment)
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Jules Bordet Institute
ClinicalTrials.gov Identifier:
NCT01301040
First received: February 18, 2011
Last updated: August 29, 2013
Last verified: February 2011
  Purpose

The primary objective is to evaluate the difference in cardiac strain rate evolution in elderly early BC patients treated with (neo) adjuvant anthracycline-based chemotherapy compared with a non-anthracycline regimen (Taxotere-cyclophosphamide) CT.

This study also will compare the serum biomarkers profile during and after the (neo) adjuvant CT in both treatment arms, assess whether MRI allows detecting earlier than standard echocardiography the signs of cardiotoxicity, during and after adjuvant (neo) CT, assess whether brain PET-CT allows detecting regional functional impairment in patients receiving CT, evaluate cognitive function before and after (neo) adjuvant CT in both treatment arms, evaluate distress and functional autonomy before and after (neo) adjuvant CT in both treatment arms, evaluate psychological state and burden of primary caregivers before and after (neo) adjuvant CT in both treatment arms, evaluate primary caregivers abilities to detect patients' distress and functional autonomy before and after (neo) adjuvant CT in both treatment arms, evaluate the short and long-term toxicity profile of the regimens, estimate the 10-year risk of relapse and/or death using the Adjuvant!Online tool, and estimate the Framingham risk score for Hard Coronary Heart Disease (10-year risk).


Condition Intervention Phase
Breast Cancer
Drug: epirubicin, cyclophosphamide, docetaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Early Detection of Chemotherapy Induced Cardiac Damage in Elderly Patients With Early Breast Cancer: a Randomized Phase II Trial Comparing (Neo) Adjuvant Epirubicin-cyclophosphamide (EC) Versus Docetaxel (Taxotere)-Cyclophosphamide (TC.)

Resource links provided by NLM:


Further study details as provided by Jules Bordet Institute:

Primary Outcome Measures:
  • The difference between cardiac strain rates measured at baseline and after 4 cycles of chemotherapy. [ Time Frame: Before chemotherapy, after chemotherapy, at 6 months, one , two and 3 years from randomization. ] [ Designated as safety issue: Yes ]

    The primary null hypothesis is that the means are equal versus the alternative hypothesis that the means are different. We plan to perform the comparison using a two-sided Student's t-test with α=5%. The power of the study to detect the difference described below has been set at 90%.

    One hundred twenty patients candidate to receive neoadjuvant or adjuvant CT for early BC will be randomized 1:1 to receive either epirubicin-cyclophosphamide (EC) or docetaxel (Taxotere) -cyclophosphamide (TC) for 4 cycles.



Enrollment: 2
Study Start Date: March 2011
Estimated Study Completion Date: March 2016
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Epirubicin/Cyclophosphamide
Treatment arm 1: EC - epirubicin (100mg/m2 IV) and cyclophosphamide (600mg/m2 IV) every 3 weeks for 4 cycles
Drug: epirubicin, cyclophosphamide, docetaxel
  • Treatment arm 1: EC - epirubicin (100mg/m2 IV) and cyclophosphamide (600mg/m2 IV) every 3 weeks for 4 cycles.
  • Treatment Arm 2: TC - docetaxel (75mg/m2 IV) and cyclophosphamide (600mg/m2 IV) every 3 weeks for 4 cycles.
Other Names:
  • Docetaxel: Taxotere
  • Cyclophosphamide: Endoxan
  • Epirubicin: Epirubicin Teva
Active Comparator: docetaxel/cyclophosphamide
Treatment Arm 2: TC - docetaxel (Taxotere) (75mg/m2 IV) and cyclophosphamide (600mg/m2 IV) every 3 weeks for 4 cycles.
Drug: epirubicin, cyclophosphamide, docetaxel
  • Treatment arm 1: EC - epirubicin (100mg/m2 IV) and cyclophosphamide (600mg/m2 IV) every 3 weeks for 4 cycles.
  • Treatment Arm 2: TC - docetaxel (75mg/m2 IV) and cyclophosphamide (600mg/m2 IV) every 3 weeks for 4 cycles.
Other Names:
  • Docetaxel: Taxotere
  • Cyclophosphamide: Endoxan
  • Epirubicin: Epirubicin Teva

Detailed Description:

Considering that both anthracycline-based and Taxotere-cyclophosphamide CT have established efficacy in the adjuvant treatment of elderly patients with early breast cancer, and the paucity of data for early cardiac toxicities with anthracycline-based adjuvant therapy compared to non-anthracycline regimen, this is the first randomized study to evaluate early cardiac signs based on doppler myocardial imaging (DMI). The results of this study could improve the monitoring of the cardiac function of elderly patients candidates to receive adjuvant chemotherapy for early breast cancer.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  1. Patient selection criteria

    • Female aged equal or more than 65 years.
    • Histological diagnosis of early BC for which the treating physician considers (neo) adjuvant chemotherapy to be beneficial. Recommended situations are:
    • Triple negative BC if pT > 1cm.
    • HER-2 positive BC if pT1 > 1cm; and trastuzumab will be given after study chemotherapy.
    • "Luminal B" cancers defined as ER+, PgR + or neg, Ki-67 ≥ 14%, and pT1 > 1cm.
    • "Luminal A" cancers (ER+, PgR+ and Ki-67 < 14%) will be considered only if ≥ 4 nodes.
    • Poor response to a preoperative endocrine therapy.
    • WHO performance status equal or less than 1.
    • Baseline LVEF equal or more than 50% measured by echocardiography.
    • Adequate organ function including:
    • neutrophils more or equal to 1.5 x 109/L.
    • platelets more or equal to100 x 109/L.
    • bilirubin < 1.25 x upper limit of normal (ULN) for the institution.
    • transaminases: AST < 2.5 x ULN , ALT < 2.5 x ULN and alkaline phosphatase ≤ 2.5 x ULN for the institution.
    • Estimated creatinine clearance > 30ml/min (using the Crockoft and Gault formula) (See Appendix E) .
    • No previous exposure to chemotherapy in this neoadjuvant or adjuvant setting.
    • No serious cardiac illness or medical conditions as judged by the investigator including, but not confined to:Symptomatic ventricular arrhythmias,Clinical and/or ECG evidence of myocardial infarction within the last 12 months,Coronary artery disease requiring medication,High-risk uncontrolled arrhythmias,Poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg).
    • Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness.
    • No participation to other clinical trials involving therapeutic agents within the 6 weeks prior to the randomization.
    • No prior or concurrent diagnosis of cancer, except for adequately treated basocellular and squamous cell carcinoma of the skin or cervical uterine in situ tumor
    • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
    • Signed written informed consent must be given according to ICH-GCP and national/local regulations, prior to any study specific screening procedures and randomization.
  2. Caregiver selection criteria

    • to be identified by participating patients as their primary caregivers i.e the person who helps them the most to cope with cancer in their everyday life
    • to be at least eighteen years old
    • to be aware of the cancer diagnosis of the patients to be fit enough to complete the questionnaires
    • to be French speaking
    • to be free of any cognitive dysfunction.
    • to give their written informed consent as regards participation in the study.
  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: NCT01301040

Locations
Belgium
Institut Jules Bordet
Brussels, Belgium, 1000
Sponsors and Collaborators
Jules Bordet Institute
Sanofi
Investigators
Principal Investigator: Lissandra Dal Lago, MD Jules Bordet Institute
Principal Investigator: Evandro De Azambuja, MD Jules Bordet Institute
  More Information

No publications provided

Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT01301040     History of Changes
Other Study ID Numbers: IJB 11-01, 2011-000562-35
Study First Received: February 18, 2011
Last Updated: August 29, 2013
Health Authority: Belgium: Ethics Committee

Keywords provided by Jules Bordet Institute:
breast cancer, elderly, early cardiac toxicity

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Docetaxel
Epirubicin
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

ClinicalTrials.gov processed this record on July 20, 2014