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

• ClinicalTrials.gov Identifier: NCT01597414
• Recruitment Status: Completed
• First Posted: May 14, 2012
• Last Update Posted: November 17, 2022
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborator: Hoffmann-La Roche
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information

• First Submitted Date: May 7, 2012
• First Posted Date: May 14, 2012
• Last Update Posted Date: November 17, 2022
• Study Start Date: June 2013
• Actual Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 10, 2012): Progression free survival rate [ Time Frame: 6 months after patients in ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (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 (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: Elderly Metastatic Breast Cancer: Pertuzumab-Herceptin vs Pertuzumab-Herceptin-Metronomic Chemotherapy, Followed by T-DM1
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Elderly Metastatic Breast Cancer Population

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: May 10, 2012): 80
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 2022
• Actual Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Italy, Netherlands, Poland, Portugal, Sweden, United Kingdom

Administrative Information

• NCT Number: NCT01597414
• Other Study ID Numbers: EORTC-75111-10114; 2011-006342-32 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• Original Responsible Party: Same as current
• Current Study Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Original Study Sponsor: Same as current
• Collaborators: Hoffmann-La Roche

Investigators

• Study Chair: Hans Wildiers, MD; UZ Leuven, Leuven, Belgium

• PRS Account: European Organisation for Research and Treatment of Cancer - EORTC
• Verification Date: November 2022