Reform: A Randomised Pilot Study Comparing the Efficacy of 4-weekly versus 12-weekly intravenous Bisphosphonate Therapy in Women with low risk Bone Metastases from Breast Cancer using bone resorption markers

Official Title

A Randomised Pilot Study Comparing the Efficacy of 4-weekly versus 12-weekly intravenous Bisphosphonate Therapy in Women with low risk Bone Metastases from Breast Cancer using bone resorption markers

Summary:

Bone is the most common site of metastases in breast cancer patients. Women with breast cancer that has spread to bone are treated with a drug called pamidronate (a bisphosphonate). Extensive research has shown that this treatment can prevent and delay complications resulting from spread of breast cancer to bones. At present, all patients with metastatic breast cancer to bone are treated with the same dose and frequency (currently 3-4 weekly) of pamidronate regardless of the extent of their disease involved in their bones. This study aims to show that in women with low levels of bone involvement, administering pamidronate once every 12 weeks (12-weekly) is therapeutically equivalent to administering the drug once every 3-4 weeks (3-4 weekly).

Trial Description

Primary Outcome:

  • To demonstrate that the administration of pamidronate once every 12 weeks is equivalent to 3-4 weekly administration.

Secondary Outcomes:

  • To evaluate the clinical efficacy of 4-weekly versus 12-weekly intravenous pamidronate therapy in women with bone metastases from breast cancer as reflected by self-reported pain using the Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy-Bone Pain (FACT-BP) questionnaires.
  • To evaluate the clinical efficacy of 4 weekly versus 12 weekly intravenous pamidronate therapy in women with bone metastases from breast cancer as reflected by the number of symptomatic SREs in patients in each study group as well as changes in urinary NTx (a different bone marker similar to sCTx).
  • To find point estimates for loss of bisphosphonate control and drop-out rate prior to sample size calculation of larger studies.

A prospective, randomised, pilot study will be conducted. 40 patients, already receiving 3-4 weekly pamidronate will undergo testing for serum C-Telopeptide (sCTx), a bone marker that independtly correlates with fracture risk. Patients with baseline sCTx  <600 ng/L that also meet all other eligibility criteria will be randomised to receive either 3-4 weekly pamidronate (depending on other systemic therapies the patient is receiving [i.e., if patient is receiving chemotherapy every 3 weeks then the pamidronate too can be administered 3 weekly]) or a 12 weekly regimen. Note that all patients will have sCTx measured 4 weeks after study initiation to ensure that subjects with rapidly rising bone breakdown markers (i.e., sCTx) are offered the 3-4 weekly dose. Patients in both study groups will be monitored for changes to their sCTx. sCTx will be measured on weeks 4, 12, 24 and 48 of the study. If the sCTx level in any subject in the 12 weekly arm rises above their allocated band, a repeat test will be carried out 4 weeks later. If the results of the second test confirms this rise, the subject will be converted to a 3-4 weekly regimen. When sCTx is evaluated, excluding week 4,  urine will also be collected and a number of questionnaires assessing pain scores will be administered.

Hypothesis:

The null hypothesis states that the proportion of patients who move from a lower risk to a higher risk CTx-category (i.e. < 400 to [400 – 600] or [400 – 600] to ≥ 600) will not be equivalent between 3-4-weekly and 12-weekly administration of bisphosphonates.

Significance:

Through completion of this project we aim to determine if women with metastatic breast cancer and low bone-involvement can be treated safely with less frequent doses of bisphosphonates (e.g., pamidronate), thus reducing their exposure to potential side effects. Since this is a pilot study, the findings will be used to apply for funding for a larger peer-reviewed grant. This has significant impact on the management of bone metastases in this population, and may in fact have cost-saving implications for both the health care system (in terms of funding for bisphosphonates) and for the patient (in terms of decreased visits to the cancer centre for treatment).

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Resources

Canadian Cancer Society

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