Study of Denosumab as Adjuvant Treatment for Women With High Risk Early Breast Cancer Receiving Neoadjuvant or Adjuvant Therapy (D-CARE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01077154
First received: February 4, 2010
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

Rationale: For women with early-stage breast cancer, bone is a frequent site of relapse, and most women with advanced breast cancer will eventually develop disease in the bone.

Denosumab, a fully human monoclonal antibody that specifically inhibits RANK ligand, may have the potential to interrupt the hypothetical "vicious cycle" of cancer-induced bone destruction and tumor cell expansion through the bone. It is not yet known if denosumab may prevent disease recurrence in the bone or in any other part of the body.

Purpose: This randomized phase 3 trial is studying the effect of denosumab to see if it can prevent disease recurrence in the bone or in any other part of the body, when it is given as adjuvant therapy for women with early-stage breast cancer, who are at high risk of disease recurrence.


Condition Intervention Phase
Breast Cancer
Drug: Placebo
Drug: Denosumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 3 Study of Denosumab as Adjuvant Treatment for Women With Early-Stage Breast Cancer at High Risk of Recurrence (D-CARE)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Bone metastasis-free survival [ Time Frame: 6 years, 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 6 years, 3 months ] [ Designated as safety issue: No ]
  • Distant recurrence-free survival [ Time Frame: 6 years, 3 months ] [ Designated as safety issue: No ]
  • Safety and tolerability of denosumab [ Time Frame: 6 years, 3 months ] [ Designated as safety issue: Yes ]
  • Disease-free survival [ Time Frame: 6 years, 3 months ] [ Designated as safety issue: No ]

Enrollment: 4509
Study Start Date: May 2010
Estimated Study Completion Date: October 2021
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab
Patients will receive denosumab as a subcutaneous injection (under the skin), and will take daily calcium and vitamin D supplementation, for up to 5 years.
Drug: Denosumab
120mg subcutaneously (SC) once monthly for 6 months. 120mg SC every 3 months for the next 4 and a half years. Oral calcium (at least 500 mg) and vitamin D (at least 400 IU) for 5 years.
Placebo Comparator: Placebo
Patients will receive placebo as a subcutaneous injection (under the skin), and will take daily calcium and vitamin D supplementation, for up to 5 years.
Drug: Placebo
120mg SC once monthly for the first 6 months. 120mg SC every 3 months for the next 4 and a half years. Oral calcium (at least 500 mg) and vitamin D (at least 400 IU) for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed, AJCC stage II or III breast cancer
  • High risk of breast cancer recurrence, defined as documented evidence of one or more of the following criteria: i) Biopsy evidence of breast cancer in regional lymph node(s) LN (node- positive disease) Nodal micrometastases only are not considered node positive ii) Tumor size > 5cm (T3) or locally advanced disease (T4)
  • Documented pathological evaluation of the breast cancer for hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and HER-2 status
  • Subjects must be receiving or be scheduled to receive standard of care systemic adjuvant or neoadjuvant chemotherapy and/or endocrine therapy and/or HER-2 targeted therapy
  • For subjects receiving adjuvant therapy only, subjects must have undergone complete resection of the primary tumor with clean surgical margins, or subjects must have undergone resection of the primary tumor and be scheduled for further treatment of the primary tumor with curative intent.

Definitive treatment must be planned to be completed within approximately 9 months of randomization

  • For subjects receiving adjuvant therapy only, time between definitive surgery and randomization must be ≤ 12 weeks. Definitive surgery may include secondary interventions (e.g. to clear inadequate surgical margins)
  • For subjects receiving adjuvant therapy only, subjects with node positive disease must have undergone treatment of axillary LN with curative intent, or subjects must be scheduled for further treatment of regional lymph nodes with curative intent. Definitive treatment must be planned to be completed within approximately 9 months of randomization
  • For subjects receiving adjuvant therapy only, subjects must not have received prior neoadjuvant treatment. Endocrine treatment for less than 30 days prior to surgery is not considered prior neoadjuvant treatment
  • For subjects receiving neoadjuvant therapy only, time between start of neoadjuvant treatment and randomization must be ≤ 8 weeks
  • For subjects receiving neoadjuvant therapy only, subjects must be scheduled to undergo definitive treatment (including surgery and/or radiotherapy) with curative intent within approximately 9 months of starting neoadjuvant treatment
  • Female subjects with age ≥ 18 years
  • Subjects with reproductive potential must have a negative pregnancy test within 14 days before randomization
  • Serum calcium or albumin-adjusted serum calcium ≥ 2.0 mmol/L (8.0 mg/dL) and ≤ 2.9 mmol/L (11.5 mg/dL)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Written informed consent before any study-specific procedure is performed

Exclusion Criteria:

  • Prior or current evidence of any metastatic involvement of any distant site
  • History of breast cancer (other than ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS]) prior to the current diagnosis
  • Osteoporosis requiring treatment at the time of randomization or treatment considered likely to become necessary within the subsequent six months
  • Any prior or synchronous malignancy (other than breast cancer), except i) Malignancy treated with curative intent and with no evidence of disease for ≥ 5 years prior to enrollment and considered to be at low risk for recurrence by the treating physician ii) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Active infection with Hepatitis B virus or Hepatitis C virus
  • Known infection with human immunodeficiency virus (HIV)
  • Prior history or current evidence of osteomyelitis/osteonecrosis of the jaw
  • Active dental or jaw condition which requires oral surgery
  • Planned invasive dental procedure for the course of the study
  • Non-healed dental or oral surgery
  • Use of oral bisphosphonates within the past 1 year
  • Prior or current IV bisphosphonate administration
  • Prior administration of denosumab
  • Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or investigational drug study(s), or subject is receiving other investigational agent(s)
  • Subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment.
  • Subject is of child bearing potential and is not willing to use, in combination with her partner, 2 highly effective methods of contraception or abstinence during treatment and for 7 months after the end of treatment
  • Subject has known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, calcium, or vitamin D)
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
  • Any major medical or psychiatric disorder that may prevent the subject from completing the study or interfere with the interpretation of the study results
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01077154

  Show 461 Study Locations
Sponsors and Collaborators
Amgen
Daiichi Sankyo Inc.
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01077154     History of Changes
Other Study ID Numbers: 20060359
Study First Received: February 4, 2010
Last Updated: January 7, 2014
Health Authority: Mexico: Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)
Peru: INS (Instituto Nacional de Salud)
Phillippines: the Bureau of Food and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: Instituto Nacional da Farmácia e do Medicamento (INFARMED)
Romania: National Medicines Agency
Russia: Federal Service for Surveillance in the field of Healthcare and Social Development (a body of the Ministry of Health)
Serbia: Medicine and Medical Devices Agency of Serbia
Slovakia: Štátny ústav pre kontrolu lieciv
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration
Taiwan: Department of Health
Latvia: State Agency of Medicines
Malaysia: National Pharmaceutical Control Bureau
Turkey: The Ministry of Health of the Republic of Turkey
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Argentina: ANMAT (Administracion Nacional de Medicamentos Alimentos y Tecnologia Medica)
Australia: Therapeutic Goods Administration
Belgium: Service Public Federal Sante Publiquest, Securite de la Chaine alimentaire et Environnement
Brazil: ANVISA (Agência Nacional de Vigilância Sanitária)
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Chile: Instituto De Salud Pública de Chile (ISP)
China: Food and Drug Administration
Czech Republic: Statni ustav pro kontrolu leciv
Denmark: Laegemiddelstyrelsen
European Union: EMEA
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Greece: Ministry of Health & Social Solidarity, National Organization for Medicines
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
Israel: Ministry of Health
Italy: Local Ethics Committees

Keywords provided by Amgen:
Early Stage Breast Cancer
Bone Metastasis
Adjuvant treatment
Neoadjuvant treatment
Denosumab
Stage II breast cancer
Stage III breast cancer
Stage IIA breast cancer
Stage IIB breast cancer
Stage IIIA breast cancer
Stage IIIB breast cancer
Stage IIIC breast cancer
Early breast cancer
Breast Tumors
Breast Neoplasms

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on April 15, 2014