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)

Study ID
STU 062010-181

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • UT Southwestern Ambulatory Services
  • UT Southwestern University Hospital—St. Paul
  • UT Southwestern University Hospital– Zale Lipshy
  • Parkland Health & Hospital System

Contact
Damaris Dotson
214-648-4981
damaris.dotson@utsouthwestern.edu

Principal Investigator
Hsiao-Ching Li

Summary

This is an international, phase 3, randomized, double-blind, placebo-controlled study in women with early-stage (stage ii or iii) breast cancer at high risk of disease recurrence.

We plan to consent about 25 people at uT Southwestern or Parkland Health and Hospital System in order to have 20 subjects that complete the protocol. This study also is taking place at a number of other medical facilities throughout the united States and/or other countries. approximately 4,500 subjects will be randomized in a 1:1 ratio to receive denosumab 120 mg or matching placebo subcutaneously (SC) every 4 weeks (Q4W; (+-) 7 days) for 6 months followed by denosumab 120 mg or matching placebo SC every 3 months (Q3M; i.e. every 12 weeks (+-) 14 days) for 4[1/2]) years (approximately 54 months), for a total treatment duration of 5 years (approximately 60 months). all subjects will be required to receive vitamin D and calcium supplementation at standard doses (at least 500 mg calcium and at least 400 iu of vitamin D; see Section 6.7 of the protocol), unless documented hypercalcemia develops on study. Subjects who develop bone metastasis will permanently discontinue treatment, complete the end of Study visit, and enter follow-up upon documented evidence (per central imaging analysis).

after completing the treatment phase of the study, subjects will be followed by clinic visit or telephone contact approximately monthly for six months to assess clinical outcomes, approximately every 3 months thereafter to assess disease recurrence status and survival (until documented evidence of bone metastasis), and approximately every 6 months thereafter to assess survival, for up to 10 years (120 months) from the date of randomization.

Randomization will be stratified based on:
1.Breast cancer therapy / Lymph node (Ln) status: neo-adjuvant therapy / any Ln status versus [vs] adjuvant therapy / Ln negative (based on axillary Ln dissection, or based on sentinel node [Sn] status) vs adjuvant therapy / Ln positive
2.Hormone receptor (estrogen receptor [eR]/ progesterone receptor [PR]) status: eR and/or PR positive vs eR and PR negative
3.Human epidermal growth factor receptor 2 (HeR-2) status: HeR-2 positive vs HeR-2 negative
4.age: [Less Than] 50 vs [GreaterThanorequalTo] 50
5.Geographic Region: Japan vs other

Participant Eligibility

1. Histologically confirmed, AJCC stage II or III breast cancer See Appendix E for breast cancer grading and staging information
2. High risk of breast cancer recurrence, defined as documented evidence of one or more of the following criteria:

* Biopsy evidence of breast cancer in regional LN (node positive disease)
Nodal micrometastases only are not considered node positive

* Tumor size > 5 cm (T3) or locally advanced disease (T4) See Appendix E for breast cancer grading and staging information

3. Documented pathological evaluation of the breast cancer for hormone receptor (ER and PR) status and HER-2 status
4. 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
5. For subjects receiving adjuvant therapy only:

* Subjects must have undergone complete treatment of the primary tumor with clean surgical margins, or
Subjects must have undergone treatment of the primary tumor and be scheduled for further resection of the primary tumor with curative intent after completion of chemotherapy. Definitive treatment must be planned to be completed approximately 9 months of randomization

* Time between definitive surgery and randomization must be <=12 weeks Definitive surgery may include secondary interventions (e.g. to clear inadequate surgical margins)

* Subjects with node positive disease must have undergone radical treatment of axillary LN with curative intent, or
Subjects must be scheduled for further treatment of regional lymph nodes with curative intent after completion of chemotherapy. Definitive treatment must be planned to be completed approximately 9 months of randomization

* Subjects must not have received prior neoadjuvant treatment
Endocrine treatment for less than 30 days prior to surgery is not considered prior neoadjuvant treatment
6. For subjects receiving neoadjuvant therapy only

* Subjects must have tumor size > 5 cm (T3) or locally advanced disease (T4) or biopsy-proven lymph node involvement

* Time between start of neoadjuvant treatment and randomization must be <= 8 weeks

* Subjects must be scheduled to undergo definative treatment (including and/or radical radiotherapy) with curative intent within approximately 9 of starting neoadjuvant treatment
Definitive surgery may include secondary interventions (e.g. to clear inadequate surgical margins)
7. Female subjects with age >= 18 years
8. Subjects with reproductive potential must have a negative pregnancy test within 14 days before randomization
9. Serum calcium or albumin-adjusted serum calcium >= 2.0 mmol/L (8.0 mg/dL) and <= 2.9 mmol/L (11.5 mg/dL)
10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
11. Written informed consent before any study-specific procedure is performed