ADC-induced Neurotoxicity Treated With Duloxetine

NCT06551051 | Recruiting Phase 2 DMC

• 1 other identifier: CIPN-ADC-001
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Duloxetine may lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether duloxetine is effective in treating peripheral neuropathy caused by antibody-drug conjugate. PURPOSE: This single arm phase II trial is studying duloxetine to see how well it works in treating peripheral neuropathy caused by antibody-drug conjugate in patients with cancer.

Conditions

Solid Tumour

Keywords

ADC; Neurotoxicity; Duloxetine

Outcome Measures

Primary Outcomes (1)

• Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale

  FACT-GOG-NTx scale neurotoxicity score (duloxetine treatment day 0 and 36) (4-point decrease in neurotoxicity score). The FACT-GOG-NTx scale, is a tool used to assess the symptoms of chemotherapy-induced peripheral neuropathy (CIPN). This scale consists of 11 items, each item is scored on a 5-point scale (0=not at all, 4=very much), with a higher total score indicating more severe CIPN symptoms. In the study, the Minimal Clinically Important Difference (MCID) for the FACT-GOG-NTx scale was estimated to be between 1.38 and 3.68, which means that changes within this range are considered to be clinically meaningful. FACT/GOG-NTx provides a targeted assessment of symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity.

  Day0 and Day36

Secondary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  16 months

• Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale

  3 months

• Numerical rating scale

  Day0 and Day36

• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

  Day0 and Day36

• Neurotoxicity score assessed by CTCAE 5.0 scale

  Day0 and Day36

Study Arms (1)

duloxetine

EXPERIMENTAL

Patients were treated with duloxetine at a recommended dose of 40mg/day, increasing to a maximum dose of 60mg/day after seven days of non-significant discomfort.

Drug: duloxetine

Interventions

duloxetine DRUG

Patients were treated with duloxetine at a recommended dose of 40mg/day, increasing to a maximum dose of 60mg/day after seven days of non-significant discomfort.

Also known as: duloxetine hydrochloride

duloxetine

Eligibility Criteria

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

You may qualify if:

• aged ≥ 18 years;
• patients with a diagnosis confirmed by histological and/or cytological examination combined with imaging or ultrasound assessment of various advanced cancers;
• consent to treatment;
• ECOG score: 0 to 2;
• have a recent treatment regimen that includes an ADC class of drug and experience a resulting grade 2 or higher peripheral neurotoxicity that has been discontinued, and grade 2 or higher peripheral neurotoxicity that has lasted for more than 28 days; and the tumour remains stable in the short term, and may be treated without the use of drugs that can cause peripheral neurotoxicity (ADCs, platinums, paclitaxels, etc.) for a period of two months.
• Have adequate organ function:
• (1) blood routine: Absolute Neutrophil Count (ANC) 1.5×109/L, Platelet (PLT) ≥70×109/L, Hemoglobin (HGB) ≥80g/L; (2) Liver function: serum Total Bilirubin (TBIL) ≤1.5×Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≥1.5×Upper Limit of Normal Value (ULN). Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3×ULN; serum albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN; after routine hepatoprotective treatment meeting the above criteria, and can be stabilised for at least 1 week after evaluation by the investigator can be enrolled; 3) Renal function: serum creatinine (Cr) ≤ 2 × ULN or creatinine clearance ≥ 30 mL/mi (applying the standard Cockcroft-Gault formula); 7. a predicted survival of ≥ 3 months; and tumour stability in the near future. 8. ability to comply with study visit schedules and other protocol requirements.

You may not qualify if:

• peripheral neurotoxicity of grade 2 or higher has occurred with platinum-containing paclitaxel chemotherapy prior to prior ADC class administration, and the toxicity has not significantly worsened before or after ADC administration;
• patients with severe diabetes mellitus and peripheral vascular disease;
• patients with a history of neuropathy due to any type of nerve compression (e.g., carpal tunnel or tarsal tunnel syndrome, radiculopathy, spinal stenosis, brachial plexopathy), severe depression, suicidal ideation, bipolar disorder, alcoholism, and severe eating disorders
• active or uncontrolled serious infections (≥ CTCAE grade 2 infections) requiring administration of systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infections.
• renal failure requiring haemodialysis or peritoneal dialysis;
• those with a history of immunodeficiency, including being HIV-positive or suffering from other acquired or congenital immunodeficiency diseases, or with a history of organ transplantation
• those with severe nausea, headache, insomnia, fatigue, drowsiness, dry mouth, dizziness and constipation
• those with a history of active tuberculosis
• uncontrolled, still need repeated drainage appearing ascites, pericardial effusion, pleural effusion;
• research treatment related:
• patients who have undergone major organ transplantation
• those who have undergone major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to the start of study treatment; or those who have longstanding unhealed wounds or fractures
• those who have experienced a severe hypersensitivity reaction following the use of monoclonal antibodies; those with known hypersensitivity to active ingredients or excipients such as the study drug;
• those who are participating or have participated in other clinical studies within 4 weeks prior to the start of the study
• those with a history of severe allergy

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Cancer center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Neurotoxicity Syndromes

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Hongxia Wang, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sheng Zhang, PhD

CONTACT

021-64175590; wozhangsheng@hotmail.com

Hongxia Wang, PhD

CONTACT

021-33988888; whx365@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 9, 2024
• First Posted: August 13, 2024
• Study Start: August 6, 2024
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)