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Elderly Metastatic Breast Cancer: Pertuzumab-Herceptin vs Pertuzumab-Herceptin-Metronomic Chemotherapy, Followed by T-DM1

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01597414
Recruitment Status : Active, not recruiting
First Posted : May 14, 2012
Last Update Posted : March 13, 2019
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information
First Submitted Date  ICMJE May 7, 2012
First Posted Date  ICMJE May 14, 2012
Last Update Posted Date March 13, 2019
Study Start Date  ICMJE June 2013
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2012)
Progression free survival rate [ Time Frame: 6 months after patients in ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2013)
  • Overall survival
  • Breast cancer specific survival
  • Tumor response rate as measured by RECIST v1.1
  • Evolution of HRQoL as assessed by EORTC QLQ-C30 and ELD 14 [ Time Frame: Up to 1 year after treatment start ]
  • Evolution of geriatric assessment [ Time Frame: Up to 1 year after treatment start ]
  • if T-DM1: progression free survival rate [ Time Frame: 6 months after start of T-DM1 treatment ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2012)
  • Overall survival
  • Breast cancer specific survival
  • Tumor response rate as measured by RECIST v1.1
  • Evolution of HRQoL as assessed by EORTC QLQ-C30 and ELD 15 [ Time Frame: Up to 1 year after treatment start ]
  • Evolution of geriatric assessment [ Time Frame: Up to 1 year after treatment start ]
  • if T-DM1: progression free survival rate [ Time Frame: 6 months after start of T-DM1 treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Elderly Metastatic Breast Cancer: Pertuzumab-Herceptin vs Pertuzumab-Herceptin-Metronomic Chemotherapy, Followed by T-DM1
Official Title  ICMJE Pertuzumab + Trastuzumab (PH) Versus PH Plus Metronomic Chemotherapy (PHM) in the Elderly HER2+ Metastatic Breast Cancer Population Who May Continue on T-DM1 Alone Following Disease Progression While on PH / PHM: an Open-label Multicentre Randomized Phase II Selection Trial of the EORTC Elderly Task Force and Breast Cancer Group
Brief Summary

Chemotherapy and HER2 targeted agents can improve survival significantly in metastatic breast cancer. Chemotherapy however is associated with significant side-effects and can impact on Quality of Life and functionality in older patients.

The investigators aim to establish HER2 targeted regimens with minimal toxicity in order to delay or even avoid the use of classical chemotherapy because of competing risks of death in this frail/elderly patient group.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Elderly Metastatic Breast Cancer Population
Intervention  ICMJE
  • Drug: Pertuzumab + trastuzumab

    Trastuzumab: loading dose of 8 mg/kg of body weight on cycle 1, followed by a maintenance dose of 6 mg/kg every 3 weeks.

    Pertuzumab: loading dose of 840 mg on cycle 1, followed by 420 mg for subsequent cycles, every 3 weeks.

    if T-DM1: 3.6 mg/kg IV, every 3 weeks.

  • Drug: Pertuzumab + trastuzumab + metronomic chemotherapy
    Pertuzumab and trastuzumab will be administered as in arm A. Cyclophosphamide: daily dose of 50 mg/day. if T-DM1: as in arm A
Study Arms  ICMJE
  • Active Comparator: Pertuzumab + trastuzumab (PH)
    Pertuzumab + trastuzumab. After progression,patients will be given the option of receiving T-DM1
    Intervention: Drug: Pertuzumab + trastuzumab
  • Experimental: PH + metronomic chemotherapy (PHM)
    Pertuzumab + trastuzumab + metronomic chemotherapy. After progression,patients will be given the option of receiving T-DM1
    Intervention: Drug: Pertuzumab + trastuzumab + metronomic chemotherapy
Publications * Wildiers H, Tryfonidis K, Dal Lago L, Vuylsteke P, Curigliano G, Waters S, Brouwers B, Altintas S, Touati N, Cardoso F, Brain E. Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer (EORTC 75111-10114): an open-label, randomised, phase 2 trial from the Elderly Task Force/Breast Cancer Group. Lancet Oncol. 2018 Mar;19(3):323-336. doi: 10.1016/S1470-2045(18)30083-4. Epub 2018 Feb 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 10, 2012)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with histologically proven HER-2 positive
  • Newly diagnosed or recurrent (after surgery) stage IV disease (TNM/AJCC v.7).
  • Patients must have measurable (RECIST v. 1.1) or evaluable disease
  • Performance status (PS) 0-3 (WHO)
  • Age ≥ 70 years of age, or ≥ 60 years old with required number of dependencies
  • Life expectancy of more than 12 weeks
  • Previous adjuvant chemotherapy/anti HER-2 therapy after surgery is allowed, given that the time interval from end of previous treatment to initiation of treatment for metastatic disease is ≥ 6 months.
  • Up to one line of anti-HER therapy (trastuzumab or lapatinib) is allowed in combination with hormone therapy for hormone sensitive metastatic breast cancer.
  • Adequate organ function
  • Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

  • No brain metastases that are untreated, symptomatic, or require steroids to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to the first study treatment.
  • No prior chemotherapy for metastatic disease is allowed
  • No prior treatment with pertuzumab is allowed
  • No history of exposure to the following cumulative doses of anthracyclines:
  • Doxorubicin or liposomal doxorubicin > 360 mg/m2
  • Epirubicin > 720 mg/m2
  • Mitoxantrone > 120 mg/m2
  • Idarubicin > 90 mg/m2
  • If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
  • No history of palliative radiotherapy within 14 days of randomization
  • No history of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin
  • No current uncontrolled hypertension (persistent systolic > 180 mmHg and/or diastolic > 100 mmHg)
  • No LVEF below 50%
  • No history of significant cardiac disease defined as:
  • Symptomatic CHF (NYHA classes II-IV)
  • High-risk uncontrolled arrhythmias
  • History of myocardial infarction within 6 months prior to randomization
  • Clinically significant valvular heart disease
  • No angina pectoris requiring anti-angina treatment
  • No peripheral neuropathy of Grade ≥ 3 per NCI CTCAE version 4.0.
  • No current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C virus)
  • No major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
  • No history of receiving any investigational treatment within 28 days of randomization
  • No history of intolerance (including Grade 3-4 infusion reaction) to trastuzumab
  • No unwillingness or inability to comply with the requirements of the protocol as assessed by the investigator
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Italy,   Netherlands,   Poland,   Portugal,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01597414
Other Study ID Numbers  ICMJE EORTC-75111-10114
2011-006342-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party European Organisation for Research and Treatment of Cancer - EORTC
Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Collaborators  ICMJE Hoffmann-La Roche
Investigators  ICMJE
Study Chair: Hans Wildiers, MD UZ Leuven, Leuven, Belgium
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP