A Phase 2 Trial Exploring the Clinical and Correlative Effects of Combining Doxycycline With Bone-Targeted Therapy in Patients With Metastatic Breast Cancer
Potential candidates for this trial must have received intravenous bisphosphonate therapy
(i.e. pamidronate or zoledronic acid) or subcutaneous denosumab for at least 3 months.
Baseline patient characteristics will be recorded and screening serum PTH (to rule out
primary hyperparathyroidism) and vitamin D (25OH-vit D) will be recorded. In order to
fulfill the study objectives, serum will be taken for CTX (fasting morning blood sample),
P1NP and BSAP as well as for the optional translational studies (e.g. MMP and TIMP levels).
Optional urine will be taken for NTX. Questionnaires will also be completed for symptoms
(Brief pain inventory (BPI)  and FACT-BP ) and analgesic use (converted into an oral
Morphine-equivalent dose). The serum, urine and questionnaire data will be collected at:
baseline, weeks 4, 8, and 12. In addition, toxicity information and questions about the
occurrence of skeletal related events will be performed at baseline, weeks 4, 8 and 12. At
baseline and week 12 the patient will also have a bone marrow aspirate and trephine biopsy
performed from the posterior iliac crest. These specimens will be used for ER, PR and Her2
analysis (by FISH) and markers of apoptosis (TUNEL) and proliferation (Ki67) and also for
optional translational studies providing tumour cells are present.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary objective of this prospective study is to assess the palliative benefit (reflected through changes in validated pain scores and the bone resorption marker serum C-telopeptide) of adding doxycycline 100mg PO BID daily for 3 months to standard bone-targeted (i.e. intravenous bisphosphonate or subcutaneous denosumab) therapy in women with breast cancer and bone metastases.
Weeks 4, 8 and 12 from starting study treatment
Mark Clemons, FRCP
The Ottawa Hospital Cancer Centre
Canada: Health Canada