Proof of Principle Study Evaluating Gonyautoxins NEURO SERUM, on Chemotherapy-induced Peripheral Neuropathy

Description

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 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. 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:

1. Evaluate the improvement of overall neurological examination as assessed by the clinical version of Total Neuropathy Score (TNSc)
2. Evaluate the improvement of manipulative dexterity and agility as assessed by the nine-hole pegboard test (NHPT).
3. Evaluate the improvement in patient reported symptoms as assessed by the Patient Neuropathy Questionnaire (PNQ).
4. 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.

The study procedures include:

1. Screening Assessments
2. Pre-treatment / Baseline Assessments (D1)
3. D7 (± 1 day) - Assessments during Treatment
4. D14 (± 1 day) - Assessments during Treatment
5. D21 (± 1 day) - Assessments during Treatment
6. End of Treatment (D28 + 3 days)
7. Safety Follow-up Visit (30 ± 7 days from the last dose)

A patient will have responded to the CIPN in the study if there is a documented improvement of 30% (two sizes of evaluator) and / or normalization of the baseline pretreatment assessment as assessed by the Semmes-Weinstein monofilament test. A patient will have progressed CIPN in the study if there is a documented worsening in tactile sensation assessed by the Semmes-Weinstein monofilament test. Worse tactile sensation is defined as the change in one (1) size of the monofilament evaluator.

Details