Sodium bicarbonate for tumour-related pain
A phase I/II study of oral sodium bicarbonate as adjuvant for pain reduction in patients with tumour-related pain.
- Blood cancer
- Solid tumours
Why this trial?
One of the most debilitating and demoralising complications in cancer is pain. Cancer pain is frequently difficult to control even with high doses of narcotics. Both cancer-induced pain and the effects of the narcotics are major factors in reducing the quality of life in cancer patients.
In a study from Breivik (2009), the overall prevalence of pain among patients with cancer was 84%. Among patients who reported pain, the prevalence of moderate to severe pain was 94% and the prevalence of severe pain was 43%. In addition, 3% of patients reported having experienced the worst imaginable pain.
This trial was supported as an initial step to determine the maximum tolerated dose (MTD) based on a rather direct outcome measurement (pain). If it were feasible to obtain the extrapolated required doses from mice experiments, the effects of pH manipulation on metastasis in humans will be explored in further studies.
Why this drug?
In recent years, it is becoming evident that tumour-related bone pain involves the reduction of peritumoral pH and activation of pain receptors. It is generally agreed that low pH surrounding metastatic lesions activates acid-sensing ion channels, or ASICs.
Pre-clinical data shows that lowering the pH (and increasing acidity) in cancer cell cultures increases the incidence of metastases in mice that are injected with those cultures. Also, it was shown in pre-clinical investigations that a lower pH increases factors that induce tumour invasiveness. In addition, inhibition of tumour acidity has been shown to enhance susceptibility of tumours to weak basic drugs.
Bicarbonate increases the buffering capacity of the tumour, which inhibits acidosis. Bicarbonate can neutralize tumour-derived acid without affecting systemic pH.
This is a single-institution, non-randomised phase I/II study of sodium bicarbonate in combination with standard medical management, a stable opioid regimen, for 35 patients with moderate to severe tumour-related pain due to metastatic solid malignancies or hematologic malignancies.
A 3+3 design with three dose escalations was used for phase I and a two-staged design for phase II. The primary objectives were to evaluate the safety (phase I) and efficacy (phase II) of oral sodium bicarbonate capsules as an adjuvant pain reliever. The researchers tried to determine the MTD and reduce pain intensity by at least 30%. The entire study was to last about 36 months, 18 months for phase I and 24 months for phase II, with several follow up appointments.
This trial started in July 2013. Due to slow patient recruitment, it was closed down during phase I in February 2015 at the researchers’ request. At closing, only 2 cohorts were recruited and in total 9 patients took part in the study of which 4 completed it. Patients could hardly comply to the treatment protocol and due to the premature closure of this project, MTD was not found. A report is expected to be published in the first half of 2018.
- Dr. Amit Mahipal, H. Lee Moffitt Cancer Center, Florida, USA
- H. Lee Moffitt Cancer Center, Florida, USA
More info on clinicaltrials.gov: NCT01846429
Breivik, H., et al. (2009). Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes. Ann Oncol., 20(8), 1420-33. doi:10.1093/annonc/mdp001
Nagae, M., et al. (2007). Acidic microenvironment created by osteoclasts causes bone pain associated with tumor colonization. Journal of Bone and Mineral Metabolism, 25(2), 99-104. doi: 10.1007/s00774-006-0734-8
Sabino, M.A., et al.(2005). Pathophysiology of bone cancer pain. The Journal of Supportive Oncology, 3(1), 15-24.
Author: Kristine Beckers (Trial Manager)
Last updated: June 2018.