ADC-induced Neurotoxicity Treated With Duloxetine

NCT ID: NCT06551051

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-06
• Study Completion Date: 2025-12-30

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.

Detailed Description

This study is a single arm phase II study. The study consisted of a screening period (subjects signed informed consent up to no more than 28 days before the first treatment of the study), a treatment period (treatment termination was defined as termination of treatment for any reason, such as imaging confirmation of disease progression, intolerance of toxicities despite dose adjustments, or early withdrawal for any reason), and a follow up period (consisting of an end-of-treatment visit, a safety visit, and a survival follow up).

Conditions

Solid Tumour

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

duloxetine

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.

Group Type: EXPERIMENTAL

duloxetine

Intervention Type: 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.

Interventions

duloxetine

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.

Intervention Type: DRUG

Other Intervention Names

duloxetine hydrochloride

Eligibility Criteria

Inclusion Criteria

1. aged ≥ 18 years;

2. patients with a diagnosis confirmed by histological and/or cytological examination combined with imaging or ultrasound assessment of various advanced cancers;

3. consent to treatment;

4. ECOG score: 0 to 2;

5. 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.

6. 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.

6. renal failure requiring haemodialysis or peritoneal dialysis;

7. 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

8. those with severe nausea, headache, insomnia, fatigue, drowsiness, dry mouth, dizziness and constipation

9. those with a history of active tuberculosis

10. uncontrolled, still need repeated drainage appearing ascites, pericardial effusion, pleural effusion;

11. research treatment related:

12. patients who have undergone major organ transplantation

13. 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

14. 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;

15. those who are participating or have participated in other clinical studies within 4 weeks prior to the start of the study

16. those with a history of severe allergy

17. have a risk of bleeding, or coagulation disorders, or are receiving thrombolytic therapy

18. have a history of psychotropic substance abuse that is not amenable to cessation or have a psychiatric disorder

19. subjects with concomitant medical conditions that, in the judgement of the investigator, seriously jeopardise the safety of the subject or interfere with the completion of the study, or who are considered otherwise unsuitable for enrolment subjects who, in the judgement of the investigator, have concomitant medical conditions that, in the judgement of the investigator, seriously jeopardise the safety of the subject or interfere with the completion of the study, or who are considered otherwise unsuitable for enrolment. Past history of definite neurological and psychiatric disorders such as dementia, epilepsy, or seizure proneness

20. in the judgement of the Investigator, a concomitant medical condition (e.g., severe diabetes mellitus, thyroid disease, psychiatric illness, etc.) which is a serious risk to the safety of the subject or which interferes with the subject's ability to complete the study, or the presence of a serious and/or unstable medical, psychiatric, or other condition (including abnormalities in laboratory tests) which interferes with the safety of the patient or with the patient's ability to provide informed consent, or any psychological, family, sociological, or psychological condition which interferes with the study protocol and the follow-up plan. Psychological, familial, sociological, or geographic conditions that affect the study protocol and follow-up plan that the investigator deems unsuitable for participation in this clinical trial for any reason

Exclusion Criteria

1. 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;

2. patients with severe diabetes mellitus and peripheral vascular disease;

3. 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

4. active or uncontrolled serious infections (≥ CTCAE grade 2 infections) requiring administration of systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infections.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Hongxia Wang

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hongxia Wang, PhD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Cancer center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Sheng Zhang, PhD

Role: CONTACT

wozhangsheng@hotmail.com

021-64175590

Hongxia Wang, PhD

Role: CONTACT

whx365@126.com

021-33988888

Facility Contacts

Sheng Zhang, PhD

Role: primary

wozhangsheng@hotmail.com

021-64175590

Hongxia Wang, PhD

Role: backup

whx365@126.com

Other Identifiers

CIPN-ADC-001

Identifier Type: -

Identifier Source: org_study_id