Overview

Study to Determine Treatment Effects of Denosumab in Patients With Breast Cancer Receiving Aromatase Inhibitor Therapy

Status:
Active, not recruiting
Trial end date:
2022-07-26
Target enrollment:
0
Participant gender:
Female
Summary
The purpose of this study is to determine whether denosumab compared to placebo, will reduce the rate of first clinical fracture in women with non-metastatic breast cancer receiving (non-steroidal) aromatase inhibitor therapy.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Amgen
Collaborator:
Austrian Breast and Colorectal Cancer Study Group
Treatments:
Aromatase Inhibitors
Denosumab
Zoledronic Acid
Criteria
Inclusion Criteria for Double Blinded Phase:

- Histologically or cytologically confirmed adenocarcinoma of the breast;

- Female subjects with non-metastatic disease who are estrogen receptor (ER) and/or
progesterone receptor (PR) positive, and who have completed their treatment pathway;

- Subjects who are currently on, or will initiate an approved non-steroidal aromatase
inhibitor therapy (eg, anastrazole) in the adjuvant setting;

- Postmenopausal woman, defined as a woman fulfilling any one of the following criteria:

- Having undergone a bilateral oophorectomy;

- Age ≥ 60 years;

- Aged < 60 years meeting the following requirements:

- Follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range;

- A negative pregnancy test within 7 days prior to randomization. Subjects who have
undergone a hysterectomy do not require a pregnancy test.

- More criteria may apply.

Exclusion Criteria for Double Blinded Phase:

- Aromatase inhibitor therapy for more than 24 months;

- Prior or concurrent treatment with Selective Estrogen Receptor Modulators (eg,
tamoxifen);

- Evidence of metastatic disease;

- Current or prior intravenous (IV) bisphosphonate administration;

- Oral bisphosphonate treatment greater than or equal to 3 years continuously OR greater
than 3 months but less than 3 years unless there was a washout period of at least 1
year prior to randomization OR any use during the 3-month period prior to
randomization;

- Prior administration of denosumab;

- Known liver or renal deficiency;

- Recurrence of the primary malignancy (e.g., during the allowed interval of
pretreatment with aromatase inhibitor);

- Diagnosis of any second non-breast malignancy within the last 5 years, except for
adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma
of the cervix uteri;

- Any kind of disorder that compromises the ability to give written informed consent
and/or comply with study procedures.

Inclusion Criteria to Receive Open-label Phase Denosumab:

- Obtain signed and dated written informed consent prior to performing any
study-specific procedure;

- Subjects currently taking an approved non-steroidal AIT (eg, anastrazole) or who have
completed or discontinued AIT within 12 months prior to participation in the OLP;

- Randomized to placebo arm during the double-blind phase (as determined by unblinding
procedures);

Exclusion Criteria to Receive Open-label Phase Denosumab:

- Current or prior IV bisphosphonate administration;

- Subjects meeting the following criteria for oral bisphosphonate treatment:

- Greater than or equal to 3 years continuously,

- Greater than 3 months but less than 3 years unless subject has had a washout
period of at least 1 year prior to participation in the OLP,

- Any use during the 3-month period prior to participation in the OLP;

- Prior or concurrent treatment with SERMs (eg, tamoxifen);

- Subjects who ended treatment with investigational product (IP) prematurely in the
double-blind phase; Treatment with commercial denosumab (Prolia or Xgeva) prior to
participation in the OLP.

Eligibility for ZA substudy Inclusion Criteria

- Obtain signed and dated written informed consent prior to performing any
substudy-specific procedure

- Subjects that received OLP denosumab and completed OLP treatment

- Last OLP denosumab administration no longer than 9 months ago Exclusion Criteria

- Current or prior ZA administration.

- Subjects who ended treatment with investigational product (IP) prematurely in the
double-blind phase and OL phase

- Known sensitivity or intolerance to any of the products to be administered during the
substudy (eg, ZA, calcium or vitamin D)

- Known history of any of the following conditions either by subject self report or
chart review

- Paget's disease (bone), Cushing's disease, hyperprolactinemia or other active
metabolic bone disease

- Known history of hypocalcemia

- Major surgery, or significant traumatic injury occurring within 4 weeks prior to
randomization

- Parathyroid glands in neck surgically removed.

- Any sections of intestine removed.

- Known human immunodeficiency virus infection

- Active infection with hepatitis B or hepatitis C virus

- Known liver or renal disease as determined by the investigator and indicated by the
following criteria:

- Aspartate aminotransferase ≥ 2.5 x ULN

- Alanine transaminase ≥ 2.5 x ULN

- Serum creatinine ≥ 2 x ULN

- Creatine clearance < 35ml/min Subjects that are pregnant or breastfeeding

- All subjects with reproductive potential must have a negative pregnancy test
within 7 days before randomization

- Subjects who are osteoporotic in baseline BMD