Patient case: 56-year-old female with basal cell carcinoma; genetic feature: PTCH1

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

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.
  Subjects who receive open-label denosumab will be followed-up until completion of 36 months of treatment. Subject not receiving treatment in the open label phase will be followed for approximately 66 months after Primary analysis data cut-off date (PADCD).


Eligibility: 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.

Relevance to patient case: not relevant