Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04715542 |
| Other study ID # |
12012021 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
August 2024 |
| Est. completion date |
August 2025 |
Study information
| Verified date |
February 2024 |
| Source |
University of Bern |
| Contact |
Eliane Timm, PhD |
| Phone |
+41316848145 |
| Email |
eliane.timm[@]unibe.ch |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Chemotherapy induced peripheral neuropathy (CIPN) is one of the most limiting side effects of
chemotherapy and often leads to adaptations in the protocol of the chemotherapy including
dose reduction or even discontinuation of treatment. In general, the symptoms of CIPN are
sensory, often distributed in a "stocking and glove" manner, and include pain, tingling, and
numbness. CIPN has a marked negative influence on quality of life of patients and their
families. It may result in serious limitations in daily functioning and affect the enjoyment,
social relationships, and ability to perform work. Current management of CIPN (i.e.
prevention and treatment) includes dose reduction or delay of chemotherapy cycles and
treatment discontinuation. Unfortunately, this reduces the chance of an effective cancer
treatment. Current guidelines of the American Society of Clinical Oncology (ASCO) on the
Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy do not conclusively
recommend any agent for the prevention of CIPN. Due to the scarcity of drugs that are
effective for preventing and treating CIPN, the distress of patients who suffer from CIPN,
and the major societal and economic costs, new approaches and effective treatment strategies
are required.
The proposed trial is a parallel, double blind, placebo controlled, randomised, phase III
superiority trial, aiming to determine whether treatment with SMP prevents incidence of or
reduces the severity symptoms of paclitaxel-induced peripheral neuropathy, as compared to
placebo.
Description:
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most limiting side effects of
chemotherapy and often leads to adaptations in the administration of the chemotherapy,
including dose reduction or even discontinuation of treatment. In general, the symptoms of
CIPN are sensory, often occuring in a "stocking and glove" manner, and most commonly
including tingling, numbness, and dysaesthesia. In addition, patients treated with agents
inducing CIPN, such as taxanes or platinum compounds, also may experience motor symptoms,
which often present as distal or general weakness, and autonomic nervous system dysfunction
(e.g. constipation or diarrhea, abnormalities of sweating, and lightheadedness and/or
dizziness with positional changes). Furthermore, patients with chronic symptoms report having
unsteady gait, putting them at higher risk of falling. CIPN has a largest impact on quality
of life and is associated with the development of psychological distress. Cancer survivors'
report long-term peripheral neuropathy symptoms with impact on symptom burden, functional
status, and quality of life. Because of the growing prevalence of cancer and of cancer
survivors, the lack of adequate treatment or preventive strategies against CIPN, as well as
the major societal and economic costs, CIPN is becoming a major issue.
According to the National Comprehensive Cancer Network (NCCN) task force report, the overall
incidence of CIPN ranges from 57 up to 83% of patients treated with paclitaxel. The incidence
and prevalence of CIPN vary among neurotoxic agents, dosing regimens (intensity and
cumulative dosing), regimen selection (e.g. combination taxanes and platinum compounds), as
well as in presence of preexisting neuropathy, comorbidities and genetic susceptibility. The
analysis of the Japanese Adverse Drug Event Report database showed that more than 50% of CIPN
associated with taxanes and platinum compounds occurred within four weeks.
After completion of chemotherapy, the prevalence of CIPN for neurotoxic chemotherapy overall
one month after finishing chemotherapy is 68%, dropping to 60% at 3 months and 30% at 6
months or more. Severe symptoms are likely to persist longer. In patients treated with
taxanes, nearly half of patients have symptoms 6 to 9 months after completing chemotherapy,
and many require years to recover, if they recover at all. In early-stage breast cancer
patients treated with paclitaxel, persistent numbness one year after treatment with
paclitaxel were reported in approximately 67% to 80% of early-stage breast cancer patients.
Two years after the end of therapy, 34.4% of breast cancer patients treated with paclitaxel
reported neuropathy symptoms, with 18.0% reporting more severe symptoms. Another study showed
that two or more years after diagnosis, 44% of breast cancer survivors treated with
paclitaxel reported long-term neuropathy symptoms.
Current standard of care Current management of CIPN (i.e. prevention and treatment) includes
dose reduction, delay of chemotherapy cycles, or treatment discontinuation. This reduces the
chance of an effective cancer treatment.
The 2014, 2020, and 2021 American Society of Clinical Oncology (ASCO) Guidelines on the
Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy did not recommend any
agent for the prevention of CIPN, and have cautiously recommended treatment of existing CIPN
with duloxetine. Preliminary evidence suggests a potential benefit from non-pharmacological
treatments in the prevention and/or treatment of chronic neuropathy including exercise,
acupuncture, cryotherapy, compression therapy, and scrambler therapy. Larger sample-sized
definitive studies are needed to confirm efficacy and clarify risks of these interventions.
Risk factors for CIPN Cumulative dose is a strong risk factor for the development of CIPN.
Other risk factors include dose per cycle, treatment schedule (number of injections),
duration of infusion, prior or concomitant chemotherapy with neurotoxic agents (i.e. vinca
alkaloids, taxanes, platinum compounds, epothilones including ixabepilone, bortezomib,
thalidomide, arsenice trioxides), development and severity of acute neuropathy syndrome or
acute pain syndrome within 1 to 4 days following the neurotoxic agent infusion, comorbid
health conditions associated with an increased risk of neuropathy (i.e. diabetes mellitus,
excess alcohol, HIV, smoking, decreased creatinine clearance, folate/vitamin B12 deficiency),
pre-existing peripheral neuropathy, older age, and higher body mass index. Other clinical
risk factors such as sedentary behavior, insomnia, fatigue, anxiety, and depression have been
shown to increase CIPN prevalence. Genetic factors may also be associated with risk of
developing CIPN.
Research question Due to the scarcity of drugs that are effective for preventing and treating
CIPN, the distress of patients who suffer from CIPN, and the major societal and economic
costs, new approaches and effective treatment strategies are required. This study
investigates the efficacy and tolerance of Stibium metallicum praeparatum 6x (Weleda), also
known as Antimon, to prevent paclitaxel-induced peripheral neuropathy as reported by
patients. As secondary outcomes, the influence on quality of life, pain, anxiety, depression,
patient's distress, sleep disorder, falls, as well as on chemotherapy treatment adherence and
dose of chemotherapy delivered is assessed.
