A Study to Investigate the Safety and Efficacy of TRK-750 for the Treatment of Patients With CIPN (Chopin Study)

NCT04282590 | Withdrawn Phase 2

• 1 other identifier: 750CNP01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of the study is:

• to assess the safety and tolerability of multiple oral (twice daily \[BID\]) doses of TRK-750 in oxaliplatin-treated colorectal cancer patients with chemotherapy-induced peripheral neuropathy (CIPN). The secondary objectives of the study are:
• to assess the efficacy of multiple oral (BID) doses of TRK-750 in reducing neuropathic symptoms, improving quality of life (QoL), and clinician-reported outcomes in oxaliplatin-treated colorectal cancer patients with CIPN.
• to study the relationship between plasma concentrations of TRK-750 and safety and efficacy variables in oxaliplatin-treated colorectal cancer patients with CIPN. The exploratory objective of this study is:
• to assess the efficacy of multiple oral (BID) doses of TRK-750 on pharmacodynamic (PD) biomarker(s) in blood, psychophysical, electrophysiological, and histological parameters of neuropathy in oxaliplatin-treated colorectal cancer patients with CIPN.

Conditions

Chemotherapy-induced Peripheral Neuropathy

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events as assessed by CTCAE v5.0

  Up to Week 28

• Proportion of patients with clinically significant changes in vital signs: supine blood pressure (mmHg), supine pulse rate (beats/min), respiratory rate (breaths/min), and oral body temperature (°C or °F)

  Up to Week 28

• Proportion of patients with clinically significant changes in electrocardiogram time intervals

  Up to Week 24

• Proportion of patients with clinically significant changes in clinical laboratory tests

  Up to Week 28

Secondary Outcomes (8)

• Absolute change and percentage change of Numerical Rating Scale (NRS) from baseline in neuropathic symptoms

  Week 12

• Proportion of patients with a reduction of at least 30% relative to baseline in neuropathic symptoms intensity on weekly average of NRS daily assessments

  Week 12

• Change from baseline in EORTC QLQ-CIPN20 patient-reported outcome scale

  Week 12

• Proportion of patients with 2 points or more improvement relative to baseline in EORTC QLQ-CIPN20 sensory subscale assessments

  Week 12

• Change from baseline in EORTC QLQ-C30

  Week 12

Other Outcomes (13)

• Change from baseline in QST parameter: cold detection threshold (°C)

  Week 12

• Change from baseline in QST parameter: warm detection threshold (°C)

  Week 12

• Change from baseline in QST parameter: mechanical detection threshold (Von Frey filament detection [g])

  Week 12

Study Arms (2)

Treatment Period 1: TRK-750, Treatment Period 2: placebo

EXPERIMENTAL

Drug: TRK-750/Placebo

Treatment Period 1: placebo, Treatment Period 2: TRK-750

EXPERIMENTAL

Drug: Placebo/TRK-750

Interventions

TRK-750/Placebo DRUG

Powder for oral solution

Treatment Period 1: TRK-750, Treatment Period 2: placebo

Placebo/TRK-750 DRUG

Powder for oral solution

Treatment Period 1: placebo, Treatment Period 2: TRK-750

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient between 18 and 80 years of age, inclusive.
• Oxaliplatin-containing chemotherapy treatment for colorectal cancer in the adjuvant setting must have been completed ≥ 3 months, but not more than 3 years, prior to Screening.
• A diagnosis of CIPN based on the following criteria:
• onset of pain of any severity in hands and/or feet after exposure to oxaliplatin AND;
• presence of painful symptoms of any severity in a symmetrical stocking and glove distribution beginning in lower extremities, which may progress to the upper extremities (the latter may or may not be present at study entry) AND;
• painful symptoms are accompanied by non-painful symptoms (e.g., tingling or numbness) in a similar distribution.
• Neuropathy of ≥ Grade 2 using the general guideline of grading scales defined in CTCAE (v5.0)
• Pain or neuropathic symptoms of CIPN for a duration of ≥ 3 months, for which the patient wants intervention.
• Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
• Females of childbearing potential will agree to use highly effective contraception (Appendix 4) from the time of signing the ICF until 90 days after the Follow-up visit. Males who are sexually active with female partners of childbearing potential will agree to use a male condom with spermicide from Day 1 until 90 days after the Follow-up visit.
• Be either CIPN pain-treatment naïve or have important side effects or inadequate relief from their current CIPN pain medication (stable over last month).
• Has not used non-pharmacological therapy for the treatment of any pain condition (e.g., chiropractic therapies, alternative medicine therapies, or acupuncture) for at least 2 weeks prior to start of the baseline days (Days -14 to -1), and a willingness to refrain from using these therapies throughout the study. The use of physical activity or other short-acting, symptomatic non-pharmacological therapy is permitted provided the patient is willing to maintain the same regimen or usage pattern consistently throughout the study.
• Able to comprehend and willing to sign an Informed Consent Form (ICF) and to abide by the study restrictions.
• Patients have a life expectancy of at least 12 months.
• An EORTC QLQ-CIPN20 score of ≥ 25 based on an average of 2 assessments during the Screening period and Day 1 prior to randomisation.

You may not qualify if:

• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, ability to complete the study, and study assessments.
• Presence of skin conditions in the affected dermatome that, in the judgement of the Investigator, could interfere with evaluation of the neuropathic pain condition.
• Presence of non-CIPN pain that may interfere with study assessments and/or self-evaluation of peripheral neuropathic pain.
• Known history of significant hypersensitivity, intolerance, or allergy.
• Peripheral neuropathy caused by tumour infiltration or compression of spinal nerves or surgical trauma.
• Active clinically significant infection
• Unstable cardiac disease or myocardial infarction within 6 months prior to study entry.
• Patients with uncontrolled major psychiatric disorders, such as major depression or psychosis.
• History of pre-existing symptomatic neuropathy prior to chemotherapy, including neuropathy due to alcoholism, vitamin B deficiency, diabetes, hypothyroidism, human immunodeficiency virus (HIV), congenital neuropathy, and toxic neuropathy.
• Female patients who are pregnant (including a positive urine pregnancy test at Screening or on Day 1) or lactating.
• Inadequate haematological function, defined as neutrophil count \< 1.0 × 10\^9/L and platelet count \< 50 × 10\^9/L with measured values of these in the clinical laboratory tests conducted at Screening. At Screening, haematology assessments may be repeated once.
• Inadequate renal function, defined as estimated glomerular filtration rate (eGFR) ≤ 59 mL/min, i.e., Creatinine Clearance (CrCl) as calculated using the Cockcroft-Gault equation with measured values of these in the clinical laboratory tests conducted at Screening:
• \[1.23 × (140 - age) × (weight in kg)\] ÷ (serum creatinine in μmol/L) - if male.
• \[1.04 × (140 - age) × (weight in kg)\] ÷ (serum creatinine in μmol/L) - if female.
• At Screening, clinical laboratory assessments may be repeated once.

Sponsors & Collaborators

• Toray Industries, Inc: lead

Study Design

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

Study Record Dates

• First Submitted: February 17, 2020
• First Posted: February 25, 2020
• Study Start: April 1, 2020
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: March 15, 2022

Record last verified: 2022-02