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Annals of Oncology
intravenously (IV) over 30–90 mins. An SC formulation of H has been developed,
which is rapidly administered (up to 5 mins), potentially improving convenience for
patients and clinical staff, and reducing administration costs. The Phase III HannaH
study (NCT00950300) demonstrated that the pharmacokinetics and efficacy of H-SC
were non-inferior to that of H-IV, meeting the co-primary endpoints. The safety
profile of H-SC was comparable and consistent with the known safety profile of
H-IV. SafeHer is designed to further evaluate the safety and tolerability of H-SC in a
broader patient population; to allow greater understanding of a range of safety data.
H-SC will be administered via one of two different routes (handheld syringe [vial
formulation] or single-use injection device [SID]; which allows self-administration).
Supportive data on SID safety and patient satisfaction with self-administration will be
collected.
Methods: SafeHer is a multicentre, international, Phase III open-label trial
(NCT01566721). The primary objective is the safety and tolerability of H-SC.
Secondary objectives include disease-free survival, overall survival and patient
satisfaction with SID administration. Immunogenicity of H and recombinant human
hyaluronidase in a subset of patients using the SID at select sites is an exploratory
objective. Planned enrolment is 2500 patients, assigned to one of two cohorts at the
investigators’ discretion ± concurrent/sequential chemotherapy. All patients will
receive H-SC at a fixed dose of 600mg regardless of body weight, for a total of 18
cycles (q3w) via injection into the thigh over a period of up to 5 minutes. Patients in
cohort A (n = 1800) will receive H-SC using handheld syringes. Patients in cohort B
(n = 700) will receive H-SC using an SID, first via assisted administration and then
self-administered (in select patients). Enrolment began in May 2012 and parallel
substudies may be performed at selected centres to evaluate medical resource
utilisation (“time and motion study”).
Disclosure: J. Gligorov: I disclose potential conflict of interest : advisory boards and
speaker honoraria for Roche laboratories. H.A. Azim: I serve on the advisory board
of Roche in the middle east. B. Ataseven: I am a Roche International Steering
Committee member for the SafeHer trial. I have received speaker honoraria from
Roche for giveing lectures. I participated in and received a travel grant from Roche
for SABCS 2011. M. Delaurentiis: I am a member of a Roche Advisory Board. F.
Herbst: I am an employee of, and am a stockholder in, F. Hoffmann-La Roche. A.
Llombart: I am a member of a Roche Advisory Board. S. Osborne: I am an employee
of Roche. X. Pivot: I am a member of Roche and GSK Advisory Boards. All other
authors have declared no conflicts of interest.
316TiP DENOSUMAB VERSUS PLACEBO AS ADJUVANT
TREATMENT FOR WOMEN WITH EARLY-STAGE BREAST
CANCER AT HIGH RISK OF DISEASE RECURRENCE
(D-CARE): AN IN PROGRESS, PHASE 3 CLINICAL TRIAL
R.E. Coleman 1 , C. Barrios 2 , R. Bell 3 , D.M. Finkelstein 4 ,H.Iwata 5 , M. Martin 6 ,
A. Braun 7 ,C.Ke 8 , T. Maniar 7 , P.E. Goss 9
1 Academic Unit of Clinical Oncology, University of Sheffield, Sheffield Cancer
Research Centre, Sheffield, UNITED KINGDOM, 2 Department of Medicine,
PUCRS School of Medicine, Porto Alegre, BRAZIL, 3 The Andrew Love Cancer
Centre, Geelong Hospital:Deakin University, Geelong, AUSTRALIA, 4 Biostatistics,
Massachusetts General Hospital, Boston, MA, UNITED STATES OF AMERICA,
5 Aichi Cancer Center, Breast Oncology, Nagoya University School of Medicine,
Nagoya, JAPAN, 6 Medical Oncology Service, Hospital General Universitario
Gregorio Marañón, Madrid, SPAIN, 7 Hematology/oncology, Amgen Inc.,
Thousand Oaks, CA, UNITED STATES OF AMERICA, 8 Biostatistics, Amgen Inc.,
Thousand Oaks, CA, UNITED STATES OF AMERICA, 9 Cancer Center,
Massachusetts General Hospital, Boston, MA, UNITED STATES OF AMERICA
Background: Bone represents approximately 40% of all first recurrences in
women with early-stage breast cancer and is a common site of distant
recurrence. In preclinical studies, RANKL inhibition significantly delays skeletal
tumour formation, reduces skeletal tumour burden, and prolongs survival of
tumour-bearing mice. Denosumab is approved for the prevention of
skeletal-related events (SREs) in patients with established bone metastases from
solid tumours.
Purpose: The D-CARE trial is designed to assess if denosumab treatment
prolongs bone metastasis-free survival (BMFS) and disease-free survival (DFS)
in the adjuvant breast cancer setting. The primary endpoint of this
event-driven trial is BMFS. Secondary endpoints include DFS and overall
survival. Additional endpoints are safety, breast density, incidence of SREs
(following the development of bone metastasis), patient reported outcomes, and
biomarkers.
Methods: In this international, randomized, double-blind, and placebo
controlled phase 3 trial, approximately 4,500 women with stage II or III breast
cancer, at high risk for recurrence and with known hormone and HER-2
receptor status, are eligible. High risk is defined as biopsy evidence of breast
cancer in regional lymph nodes, tumour size > 5 cm, (T3), or locally advanced
disease (T4). Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or
HER-2 targeted therapy, alone or in combination, must be planned. Patients
with a prior history of breast cancer (except DCIS or LCIS) or distant
metastasis, oral bisphosphonate (BP) use within 1 year of randomization, or
any intravenous BP use, are not eligible. Patients are randomized 1:1 to receive
denosumab 120 mg or placebo subcutaneously monthly for 6 months, then
every 3 months for a total of 5 years of treatment. Supplemental vitamin D (≥
400 IU) and calcium (≥ 500 mg) will be administered. The trial, sponsored by
Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154,
began enrolling patients in June 2010 and isexpectedtocompleteenrolmentin
late 2012.
Disclosure: R.E. Coleman: Other substantive relationships: Expert testimony -
Novartis. R. Bell: Advisory Board Member : Amgen. M. Martin: Advisory Board
Member amgen, roche, bayer, novartis, gsk, sanofi. A. Braun: Employee : Amgen
Inc Stock : Amgen Inc. C. Ke: Employer : Amgen Inc. Stock ownership : Amgen Inc.
T. Maniar: Employee :: Amgen Inc. Stock ownership :: Amgen Inc. P.E. Goss:
Honoraria for Pfizer and Novartis. All other authors have declared no conflicts of
interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds392 | ix115