Proof of Principle Study Evaluating the Effects of Gonyautoxins, Paralytic Shellfish Poisoning (PSP) NEURO SERUM, on Objective and Subjective Symptoms of Chemotherapy-induced Peripheral Neuropathy (CINP)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Algenis SpA
- 入组人数
- 52
- 试验地点
- 9
- 主要终点
- Evaluate the change in response caused by PSP NEURO SERUM on the tactile sensation from baseline to day 28.
研究概览
简要总结
Proof-of-concept study to assess the effects of gonyautoxins (PSP NEURO SERUM) on safety and tactile sensitivity on patients with chemotherapy-induced peripheral neuropathy (CIPN). This is a multicenter, prospective proof-of-concept study in patients with solid tumors affected by CIPN. The study will be divided into two parts: Part 1 will assess the activity and tolerability of PSP NEURO SERUM and part 2 consists of a randomized cohort that will compare the activity of PSP NEURO SERUM vs placebo. Part 2 will depend on the results of part 1. If there are less than 8 responses in part 1, the study will be interrupted, and it will not be recommended to proceed with part 2.
详细描述
A multicenter, prospective proof-of-concept study in patients with solid tumors who developed chemotherapy-induced peripheral neuropathy (CIPN) in upper limbs, equal or greater than grade 2, according to NCI-CTCAE version 5.0. Patients must have been treated with cytotoxic agents known to cause CIPN in neoadjuvant, adjuvant or palliative setting. The primary objective is to assess the effects of gonyautoxins (PSP NEURO SERUM) on tactile sensitivity and safety on patients with CIPN. The study will be divided into two parts, 1 and 2 and the investigational treatment will have a maximum duration of 4 weeks (28 days).
Part 1 is a two-stage (stage 1 and stage 2), two-cohort (C1 and C2), open-label study where up to 38 pts with G>2 CIPN secondary to taxanes (C1) and other anti-neoplastic drugs (C2) will receive PSP NEURO SERUM thrice a day for 28 days. Twelve patients will be evaluated in stage 1, expecting a 20% response (2/12) in each cohort to proceed to stage 2. If needed, additional 7 patients will be recruited to stage, expecting 4/19 response in each cohort. If the number of responses is not met in a specific cohort, recruitment will be halted. The transition to the randomized part 2 will be determined by the efficacy in part 1 (stratified analysis of C1 and C2 or overall population).
The primary objective of Part 1 is to evaluate response of the tactile sensation as assessed by the Semmes-Weinstein monofilament test and to evaluate safety and toxicity (type, frequency, grade and causality of adverse effects) of PSP NEURO SERUM according to NCI-CTCAE v5.0.
The secondary objectives of Part 1 are to:
- Evaluate the improvement of overall neurological examination as assessed by the clinical version of Total Neuropathy Score (TNSc)
- Evaluate the improvement of manipulative dexterity and agility as assessed by the nine-hole pegboard test (NHPT).
- Evaluate the improvement in patient reported symptoms as assessed by the Patient Neuropathy Questionnaire (PNQ).
- Evaluate the improvement of quality of life by using the Portuguese version of the 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC Quality of Life Questionnaire (QLQ-C30)) version.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Age ≥18 years
- •Histological diagnosis of cancer (hematologic or solid tumors).
- •Part 1: Treatment with antineoplastic agents that induce peripheral neuropathy in neoadjuvant, adjuvant, or metastatic scenario; Part 2: Treatment with taxanes peripheral neuropathy inducers in the neoadjuvant, adjuvant, or metastatic scenario.
- •Peripheral sensory neuropathy grade 2 or higher on upper limbs as per NCI-CTCAE v5.
- •and with alteration of the Semmes Weinstein monofilament test.
- •Part 1: Diagnosis of peripheral sensory neuropathy during treatment with antineoplastic agents drugs that induce peripheral neuropathy or up to 2 weeks after the last chemotherapy infusion; Part 2: Diagnosis of peripheral sensory neuropathy during treatment with peripheral neuropathy-inducing taxanes or up to 2 weeks after last chemotherapy infusion.
- •Part 1: Patients with chronic symptoms related to peripheral sensory neuropathy who have completed treatment with peripheral neuropathy-inducing antineoplastic agents for more than 2 weeks and without any exclusion criteria, may be included. Part 2: Patients with chronic symptoms related to sensory peripheral neuropathy who completed treatment with peripheral neuropathy-inducing taxanes for more than 2 weeks and no exclusion criteria, can be included.
- •Patients using neuropathic pain modulators will be allowed if there is no dose adjustments in the last 2 weeks and if sensory symptoms persist related to CIPN, or if the use is for another indication.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to
- •Documented willingness to use an effective contraceptive method while participate in the study for male patients with partners or female participants with the potential to become pregnant.
- •Part 1: Hand skin and cuticles must be intact. Part 2: Skin of hands, feet and cuticles must be intact.
排除标准
- •Prior treatment with gonyautoxins or any small molecule neurotoxins.
- •Female participants who are pregnant (positive urine pregnancy test), who have an infant they are breastfeeding, or intend to become pregnant within 3 months.
- •History of peripheral sensory neuropathy attributed to any cause other than chemotherapy.
- •Patients receiving systemic treatment that has among its common side effects (> 1%) peripheral neuropathy, or who have received the same within the last 2 weeks. The use during the study of systemic drugs such as hormone therapy (e.g. tamoxifen, aromatase inhibitor, etc), or other agents that do not have among their common side effects (>1%) peripheral neuropathy, will be allowed.
- •Patients with grade 2 CIPN with perceived improvement of symptoms.
- •Changes in neuropathic pain modulators will not be allowed.
- •Any other therapies for chemotherapy-induced peripheral neuropathy must be discontinued at least 2 weeks before the first dose of study drug.
- •Known hypersensitivity reaction to PSP Neuro serum.
- •Patients with a known or suspected shellfish allergy.
- •No dermatologic lesions on hands and feet and cuticles that might increase systemic exposure of the investigational medicinal product (IMP).
- •Distal muscle weakness and/or atrophy.
- •History of alcoholism or alcohol intake of 168g (21 units) for men and 112g (14 units) for women per week on a regular basis (time > 3 months). 1 unit = 10mL = 8g of pure alcohol.
- •Clinically significant abnormalities of glucose metabolism as defined by any of the following:
- •Diagnosis of type I or II diabetes mellitus (regardless of management) that have symptoms attributable to diabetic neuropathy pre-treatment with chemotherapy. Well-controlled diabetic patients (regardless of management), previously asymptomatic may be included.
- •Glycosylated hemoglobin (HbA1C) ≥8.0% at screening.
- •Fasting serum glucose ≥ 160 mg/dL at screening. Fasting is defined as no caloric intake for at least 8 hours.
- •Vitamin B12 deficiency defined as < 250 ng/mL.
- •Phosphate levels above upper limit of normal (ULN).
- •ECG: QTc interval (Fridericia Formula) ≥ 450ms.
- •Positive Tinel and/or Phalen test.
- •Participation in another clinical trial and any concurrent treatment with any investigational drug within 4 weeks prior to trial entry / randomization.
- •Surgery, radiotherapy, or systemic therapy that in the investigators' opinion might interfere/ worsen symptoms and the evaluation of peripheral neuropathy within 2 weeks prior to trial entry /randomization.
- •Any other finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patients at high risk from treatment complications.
- •Unresolved clinically significant toxicity from prior therapy except for alopecia.
- •Failure to adhere to study treatment and follow-up procedures.
研究组 & 干预措施
PSP NEURO SERUM
Active arm in which 26 patients will receive PSP NEURO SERUM in their hands three times a day for 28 days. Each application will consist of 1 g of PSP NEURO SERUM.
干预措施: PSP NEURO SERUM (Drug)
Placebo of PSP NEURO SERUM
Placebo arm in which 26 patients will receive Placebo PSP NEURO SERUM (same ingredients as PSP NEURO SERUM except for the active ingredient that is replace with water) in their hands three times a day for 28 days. Each application will consist of 1 g of Placebo PSP NEURO SERUM.
干预措施: Placebo PSP NEURO SERUM (Drug)
结局指标
主要结局
Evaluate the change in response caused by PSP NEURO SERUM on the tactile sensation from baseline to day 28.
时间窗: Screening and day 28
The response will be assessed using the Semmes-Weinstein monofilament test.
次要结局
- Evaluate the change in the overall neurological examination using the Total Neuropathy Score (TNSc), from baseline to day 28.(Screening and day 28.)
- Evaluate the change in patient reported symptoms from baseline to day 28.(Screening and day 28.)
- Evaluate the appearance of Adverse Events according to NCI-CTCAE v5.0 (National Cancer Institute - Commun Toxicity Criteria For Adverse Events).(Through the 28 days of the study)
- Evaluate the change of manipulative dexterity and agility from baseline to day 28.(Screening and day 28.)
- Evaluate the change in the quality of life from baseline to day 28.(Screening and day 28)
研究者
Mariane Sousa Fontes Dias
Principal Investigator
Oncoclínicas