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A Phase 2 Trial Exploring the Clinical and Correlative Effects of Combining Doxycycline With Bone-Targeted Therapy in Patients With Metastatic Breast Cancer

Phase 2
19 Years
Open (Enrolling)

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Trial Information

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) [26] and FACT-BP [27]) 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.

Inclusion Criteria:

1. Patients with metastatic breast cancer with radiologically confirmed bone

2. On intravenous bone-targeted therapy (bisphosphonate or subcutaneous (SC) denosumab)
for at least 3 months.

3. ECOG ≤ 2

4. Life expectancy >3 months.

5. No changes in the type of systemic chemotherapy, endocrine therapy or biological
therapy (i.e. trastuzumab, lapatinib) treatment in the 4 weeks prior to study entry
or anticipated changes in the 4 weeks after entering the study. (Markers of bone
formation can be affected by a change in systemic therapies).

6. Ability to provide informed consent and complete study evaluations.

Exclusion Criteria:

1. Prior hypersensitivity to either IV bisphosphonate therapy or SC denosumab,
doxycycline or tetracyclines.

2. Patients with myasthenia gravis

3. Patients taking hepatic enzymes inducers such as phenytoin, barbiturates and

4. Patients with rapidly progressive non-bone metastases for whom delaying a change in
systemic anti-cancer treatment in the first 4 weeks of the study could have a
detrimental impact on patient outcome.

5. Women of child bearing potential who are unwilling to use acceptable methods of
contraception while on study.

6. Pregnancy or lactation.

7. Clotting disorder that would preclude bone marrow aspirate and trephine biopsy.
(Patients on Fragmin or Daltaperin are allowed on study)

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

palliative benefit

Outcome Description:

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.

Outcome Time Frame:

Weeks 4, 8 and 12 from starting study treatment

Safety Issue:


Principal Investigator

Mark Clemons, FRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

The Ottawa Hospital Cancer Centre


Canada: Health Canada

Study ID:

OTT 12-05



Start Date:

April 2013

Completion Date:

November 2015

Related Keywords:

  • Pain
  • breast
  • bone pain
  • Breast Neoplasms