The main objectives are to evaluate the efficacy (as measured byprogression free survival at 6 months) of pertuzumab combined withtrastuzumab (PH) or PH plus metronomic chemotherapy (PHM) in anelderly metastatic breast cancer population, and to…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free survival rate at 6 months
Secondary outcome
Overall survival
* Breast cancer specific survival
Safety
* Toxicity (with specific attention to cardiac toxicity);
* Tumor response rate as measured by RECIST v1.1
* For those patients receiving T-DM1 after progression: toxicity, tumor
response, PFS after starting T-DM1
* Evolution of HRQoL as assessed by EORTC QLQ-C30 and ELD 15
* Evolution of geriatric assessment during treatment. This will be based
on the EORTC minimum dataset (G8, IADL and social situation), the
ADL and frailty assessment by SPPB.
-PFS outside of the brain after brain-only relapse for patients continuing on
the treatment they were receiving before brain disease progression (PH or PHM
or T-DM1)
Background summary
Given the lack of *standard* treatment for older HER-2 positive breast cancer
patients and the clear need to have active and tolerable treatment regimens for
this population, this will be the first randomized phase II trial to evaluate a
chemotherapy-free, anti-HER2-based treatment strategy. This trial will try to
answer whether PH combination could delay the use of conventional chemotherapy
for very long periods, and in a significant proportion of patients avoid its
use altogether. Integration of geriatric evaluation will assist in assessing
the benefit of therapy in different ageing populations as well as the impact of
the therapy on global functioning.
Study objective
The main objectives are to evaluate the efficacy (as measured by
progression free survival at 6 months) of pertuzumab combined with
trastuzumab (PH) or PH plus metronomic chemotherapy (PHM) in an
elderly metastatic breast cancer population, and to select attractive
treatments for further development in Phase III.
Study design
This is an open-label, multicentric, 1:1 randomized phase II selection trial
Intervention
Treatment cycles are defined as a 3 week period.
Arm A: Trastuzumab will be administered at 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 will be given at a fixed loading dose of 840 mg on
cycle 1, followed by 420 mg for subsequent cycles, every 3 weeks.
Arm B: Pertuzumab and trastuzumab will be administered as in arm A.
Cyclophosphamide should be taken orally by the patient, at a daily dose of
50 mg/day.
After progression in arm A or arm B, patients will be given the option of
receiving T-DM1. T-DM1 will be given at a dose of 3.6 mg/kg IV, every 3
weeks.
Study burden and risks
Risk: possible adverse events from therapy
Benefit: possible active and tolerable treatment
Av. Emmanuel Mounier 83/11b
Brussel 1200
BE
Av. Emmanuel Mounier 83/11b
Brussel 1200
BE
Listed location countries
Age
Inclusion criteria
-Female or male patients with histologically proven HER-2 positive (IHC 3+ or or
HER-2 gene amplification by in situ hybridization [FISH, SISH].
-Patientsmust 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 as described below :
•65 - 69 in combination with functional restriction defined as limitation
in at least 2 of 8 iADL or 1 of 6 ADL or Charlson comorbidity score > 2
•60 - 64 in combination with functional restrictions defined as
limitation in at least 3 of 8 iADL 2 of 6 ADL or Charlson comorbidity score
> 3
-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, evidenced by the following laboratory results
within 3 weeks prior to randomization: (patients with a buffer range
from the normal values of +/- 5% for hematology and +/- 10% for
biochemistry [with the EXCEPTION of Glomerular Filtration Rate] are
acceptable)
-Absolute neutrophil count > 1500 cells/mm3
-Platelet count > 100,000 cells/mm3
-Hemoglobin > 8.5 g/dL
-Total bilirubin <= 1.5 upper limit of normal (ULN)
-SGOT (AST), SGPT (ALT), and alkaline phosphatase <= 2.5× ULN (for
alkaline phosphatase limit applies in the absence of bone metastases)
-Glomerular Filtration Rate (GFR) >= 30 ml/min according to MDRD
formula or Cockcroft and Gault Formula
-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
-Before patient randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations.
-Newly diagnosed or recurrent (after surgery) stage IV disease
(TNM/AJCC v.7).
Exclusion criteria
-Current symptomatic brain metastases.
-Prior chemotherapy for metastatic disease.
-Prior treatment with pertuzumab.
-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.
-History of palliative radiotherapy within 14 days of /prior to randomization.
-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.
-Current uncontrolled hypertension (persistent systolic > 180 mmHg
and/or diastolic > 100 mmHg) (with or without medication).
-LVEF below 50%.
-History of significant cardiac disease defined as:
•Symptomatic CHF (NYHA classes II-IV, see Appendix C)
•High-risk uncontrolled arrhythmias, i.e. atrial tachycardia with a heart
rate > 100/min at rest, significant ventricular arrhythmia (ventricular
tachycardia) or higher-grade AV-block (second degree AV-block Type 2
[Mobitz 2] or third degree AV-block)
•History of myocardial infarction within 6 months prior to randomization
•Clinically significant valvular heart disease
•angina pectoris requiring anti-angina treatment
-Peripheral neuropathy of Grade >=3 per NCI CTCAE version 4.0.
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)
-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.
-History of receiving any investigational treatment within 28 days of
randomization.
-History of intolerance (including Grade 3-4 infusion reaction) to
trastuzumab.
-Unwillingness or inability to comply with the requirements of the
protocol as assessed by the investigator.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-006342-32-NL |
| CCMO | NL43797.058.13 |