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