A Study of Topical Pirenzepine or Placebo in Oncology Patients With Chemotherapy Induced Peripheral Neuropathy

NCT05488873 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: WST-PZP-005
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled adaptive study of the safety, tolerability, and exploratory efficacy of once-daily topical WST-057 administered for up to 19 weeks (or up to 24 weeks for subjects who experience a chemotherapy dose delay) to subjects who are also receiving 6 cycles (3 weeks apart) of Carboplatin AUC 5-6 and Paclitaxel 175 mg/m2 (with dose adjustment per institutional guidelines permitted).

Conditions

Chemotherapy-induced Peripheral Neuropathy

Keywords

Oncology; Peripheral Neuropathy; Chemotherapy; Carboplatin/Paclitaxel

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events as assessed by hematology and chemistry blood tests.

  Safety will be assessed by observing changes in patients' blood tests when compared to normal lab values/ranges after once daily dosing of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv5.0 will be reported.

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Incidence of Treatment-Emergent Adverse Events as assessed by vital signs (blood pressure (diastolic and systolicmmHg), heart rate (beats per minute), respiratory rate (breaths per minute).

  Safety will be assessed by observing changes in vitals signs (from baseline) in patients after daily topical doses of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be reported.

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Incidence of Treatment-Emergent Adverse Events as assessed by ECG (measuring P Wave, QRS complex, QT interval)

  Safety will be assessed by observing changes in ECG parameters (from baseline) in patients after daily dosing of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be reported.

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Incidence of Treatment-Emergent Adverse Events as assessed by a dermal assessment (Draize score (scale 0.0-4.0) of the dosing area

  Dermal safety will be assessed by observing changes in dermal scores (from baseline) in patients after daily dosing of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be reported.

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Incidence of Treatment-Emergent Adverse Events as assessed by physical examination

  Safety will be assessed by observing changes in physical examination findings (from baseline) in patients after daily dosing of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be reported.

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Incidence of Treatment-Emergent Adverse Events as assessed by tumor evaluation using RECIST v1.1

  Safety will be assessed by observing changes in tumor evaluation of radiology using RECIST v 1.1(from baseline) in patients after daily dosing of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be reported.

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

Secondary Outcomes (18)

• Visual Analogue Score (VAS)

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Neuropathy Total Symptom Score-6 (NTSS-6)

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity-13 (FACT/GOG-Ntx-13)

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Patient-Reported Outcomes Measurement Information System (PROMIS)-physical function (short form)

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

• Thermal Quantitative Sensory Testing (Cold)

  19 weeks or 24 weeks for subjects on a chemotherapy dose delay

Study Arms (2)

Placebo

EXPERIMENTAL

Participants will apply 4 mL QD Placebo topical solution

Drug: Placebo

WST-057 Active

EXPERIMENTAL

Participants will apply 4 mL QD WST-057 Active topical solution.

Drug: WST-057 Active

Interventions

WST-057 Active DRUG

WST-057 Topical Solution

Also known as: Active

WST-057 Active

Placebo DRUG

Matching Placebo Topical Solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, ages \> 18 years and older.
• Scheduled to undergo chemotherapy for an advanced or metastatic (stage 3 or 4) solid tumor with carboplatin and paclitaxel for 6 cycles of treatment. Treatment with immunotherapy agents Avastin (bevacizumab) and/or Keytruda (pembrolizumab) is permitted.
• Ability to sign informed consent and understand the nature of a placebo-controlled trial.
• ECOG Performance Status (PS) of 0, 1, or 2.
• Ability to complete patient reported outcome questionnaires by themselves.
• Life expectancy ≥ 6 months
• Females should be either not of childbearing potential as a result of surgery or menopause (1 year after onset), or of childbearing potential and must be practicing a highly effective medically acceptable method of contraception (as defined in section 8.4.4.1), including abstinence; hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device or intrauterine system; or vasectomy (partner), for at least 1 month before the screening visit and for 1 month after the last dose of study medication. If access or use of a highly effective medically acceptable method of contraception is not achievable, then a combination of barrier methods (e.g., male condom, female condom, cervical cap, diaphragm, contraceptive sponge) is acceptable. Eligible female subjects must also have a negative pregnancy test at the screening and baseline visit.
• Males must agree to the use an acceptable form of contraception (as defined in section 8.4.4.1) during sexual contact with a pregnant female or a female of childbearing potential while participating in the study (e.g., male condom with diaphragm, male condom with cervical cap, or male condom in association with spermicide).
• If diabetic, be on stable antidiabetic treatment (\> 2 months prior to screening) (oral or injectable antidiabetic therapy and/or lifestyle) that is not anticipated to change during the course of the study, except if medically required.
• Fluency (oral and written) in the language in which the standardized tests will be administered

You may not qualify if:

• Pre-existing history (with or without current symptoms) in medical history of any type of peripheral neuropathy due to any cause other than prior chemotherapy (diabetes, alcohol, toxins, neurotoxic treatments, hereditary, autoimmune, etc.).
• Anyone with prior history of severe paclitaxel hypersensitivity (including anaphylaxis) should be excluded from study enrollment. Pre-treatment is per local standard of care guidelines to prevent a paclitaxel hypersensitivity reaction. Absolute Neutrophil Count (ANC) must be at least 1500 cells/mm3 prior to paclitaxel treatment.
• Currently taking regular pain medications i.e., gabapentin, pregabalin, amitriptyline or duloxetine. (Exception: opioids, given for the short-term treatment i.e., malignant pain is acceptable. Opioids prescribed for neuropathic pain is excluded).
• Clinically significant active macrovascular disease, including a) myocardial infarction or cerebrovascular event in the prior 6 months, b) angioplasty or stenting of coronary arteries or coronary artery bypass surgery within the past \< 12 months (valve replacements are permitted as long as patient has fully recovered from the surgery), c) diagnosis of congestive heart failure of any NY heart class I-IV, d) stable or progressive angina pectoris.
• Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient.
• Vitamin E supplementation (2R-α-tocopherol or equivalent) for any reason \> 225 IU (approximately 150mg)/day ≤ 30 days prior to randomization.
• Any of the following: pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception (as defined in section 8.4.4.1).
• Head or neck cancers.
• Scheduled to undergo radiation therapy while on study.
• History of hemorrhagic stroke.
• Proliferative retinopathy or maculopathy requiring acute treatment.
• Patients requiring dialysis.
• Presence of clinically significant peripheral or autonomic neuropathy.
• Current use local (topical) anesthetics or analgesics including lidocaine, capsaicin, cannabinoid (CBD) oil/products, or compounded topical pharmaceutical agents.
• Uncontrolled treated/untreated hypertension (systolic blood pressure \[BP\] ≥ 180 or diastolic BP ≥ 100 at screening).

Sponsors & Collaborators

• WinSanTor, Inc: lead

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

MeSH Terms

Conditions

Neoplasms; Peripheral Nervous System Diseases

Interventions

Exercise

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Angela Hansen

  WinSanTor, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2022
• First Posted: August 5, 2022
• Study Start: November 22, 2022
• Primary Completion: April 26, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)