Stibium Metallicum Praeparatum D6 Versus Placebo in the Reduction of Paclitaxel-induced Peripheral Neurotoxicity (STING-CIPN)

A Randomized, Double-blind, Placebo-controlled Multicenter Study Evaluating Stibium Metallicum Praeparatum D6 for Reducing Chemotherapy-induced Peripheral Neuropathy in Breast and Gynecological Cancer Patients Receiving Paclitaxel

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 trial, aiming to determine whether treatment with SMP reduces the severity of symptoms of paclitaxel-induced peripheral neuropathy, as compared to placebo.

Study Overview

• Status: Not yet recruiting
• Conditions: Chemotherapy Induced Peripheral Neuropathy (CIPN)
• Intervention / Treatment: Drug: Placebo; Drug: Stibium metallicum praeparatum 6x

Detailed 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 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.

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.

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 D6 (Weleda), also known as Antimon, to reduce paclitaxel-induced peripheral neuropathy as reported by patients. As secondary outcomes, the influence on quality of life as well as on chemotherapy treatment adherence and dose of chemotherapy delivered is assessed.

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Silvia Erni, PhD; Phone Number: +41316841563; Email: silvia.erni@unibe.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Age ≥ 18
• Early breast cancer, ovarian cancer or other gynecological cancer
• Patients who are about to receive a treatment with paclitaxel for 12 or 18 weeks (weekly or three-weekly) as part of adjuvant or neo-adjuvant chemotherapy.
• Ability to provide informed consent as documented by signature
• Ability to read, write, and speak German

Exclusion Criteria:

• Patients with pre-existing neuropathy
• Prior chemotherapy with taxanes or other neurotoxic agents
• Concomitant medications that are known to cause neuropathy
• Pregnancy or lactation
• Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
• Patients with depression or epilepsy
• Allergy to milk protein

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline subcutaneous injection; Placebo (a saline subcutaneous injection) is chosen as comparator to the treatment group.	Drug: Placebo; Placebo will be administered with subcutaneous injections 3 times a week at 1 ampoule at 1 mL during the chemotherapy and shall be continued during 6 weeks after the end of chemotherapy . The first injection will be administered on the day of the first dose of chemotherapy, before the injection of the first dose of chemotherapy.
Experimental: Stibium metallicum praeparatum D6; Patients are treated with Stibium metallicum praeparatum D6 (subcutaneus injection), which is authorized in Switzerland and is listed by Swissmedic as an authorized anthroposophic medicinal product.	Drug: Stibium metallicum praeparatum 6x; Stibium metallicum praeparatum D6 will be administered with subcutaneous injections 3 times a week at 1 ampoule at 1 mL during the chemotherapy and shall be continued during 6 weeks after the end of chemotherapy . The first injection will be administered on the day of the first dose of chemotherapy, before the injection of the first dose of chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in neuropathy severity	Measured by the neurotoxicity subscale (NTX-subscale) of the FACT/GOG-NTX questionnaire (FACT/GOG-NTX: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, Score rage of NTX-subscale: 0-44, the higher the score, the better the QOL)	Weekly from week 1 (Baseline) - 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence and severity of paclitaxel-induced peripheral neuropathy over the whole study period	Measured by the NTX-subscale of the FACT/GOG-NTX questionnaire	12-week chemotherapy: Weekly from week 1-19 and week 24, 36, 48, 60; 18-week chemotherapy: Weekly from week 1-25, and week 30, 42, 54, 66
Oncologist's evaluation CIPN	Assessed by oncologist using the CTCAE grading system	12-week chemotherapy: Week 1, 4, 7, 10, 13, 19, 24, 36, 48, 60; 18-week chemotherapy: Week 1, 4, 7, 10, 13, 16, 19, 25, 30, 42, 54, 66
Chemotherapy adherence	Record whether all chemotherapy cycles could be administered as planned (indicate chemotherapy interruptions, dose reductions and discontinuations)	12-week chemotherapy: Week 13; 18-week chemotherapy: Week 19
Effect on Quality of life (QOL)	Assessed by the FACT-G questionnaire (FACT-G: Functional Assessment of Cancer Therapy - General, Score range: 0-108, the higher the score, the better the QOL)	12-week chemotherapy: Week 1, 7, 13, 19, 24, 36, 48, 60; 18-week chemotherapy: Week 1, 7, 13, 19, 25, 30, 42, 54, 60
Biomarker for CIPN	Detection of Neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) levels in blood serum	Week 1, 13, 19

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to study medication (I)	Assessed by self-report	12-week chemotherapy: Weekly from week 1-19; 18-week chemotherapy: Weekly from week 1-25
Adherence to study medication (II)	Assessed by returned unused medication	12-week chemotherapy: Week 19; 18-week chemotherapy: Week 25
Severe adverse events	Recorded incidence and severity of adverse events	12-week chemotherapy: Week 1, 4, 7, 10, 13, 19, 24, 36, 48, 60; 18-week chemotherapy: Week 1, 4, 7, 10, 13, 16, 19, 25, 30, 42, 54, 66

Collaborators and Investigators

• Sponsor: University of Bern
• Collaborators: University Hospital, Basel, Switzerland
• Investigators: Study Director: Ursula Wolf, Prof. Dr., University of Bern; Principal Investigator: Anton Oseledchyk, PD Dr. med., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 14, 2021
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 10, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Neuromuscular Diseases; Poisoning; Peripheral Nervous System Diseases; Neurotoxicity Syndromes
• Other Study ID Numbers: 12012021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will never be available to other researchers who are not part of the core research group. Unblinding is explicitly not foreseen for this study. Maintaining blinding until all participants complete the study protocol, the data base is locked and analysis is completed, will help retain trial integrity of this double-blinded study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No