Neoadjuvant/Adjuvant Trial of Darovasertib in Ocular Melanoma

NCT05187884 | Completed Phase 2

• 1 other identifier: NADOM
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the feasibility and tolerability of neo-adjuvant/adjuvant Darovasertib on uveal melanoma patients. Who is it for? Patients may be eligible to join this study with high-risk uveal melanoma and planned to undergo enucleation Study details: Eligible patients will undergo up to 4 weeks of treatment with Darovasertib (300mg, twice a day as a starting dose) and once determiend safe then up to 6 months after fulfilling inclusion/exclusion criteria and consent. Select patients will undergo adjuvant treatment for 6 months based on their initial response. It is hoped that this research will provide insight into the safety and tolerability of Darovasertib. Furthermore, it aims to document the pharmacodynamic and pharmacokinectic effects of Darovasertib on uveal melanoma patients.

Conditions

Ocular Melanoma

Outcome Measures

Primary Outcomes (2)

• To determine the safety of a up to a 56-day course of Darovasertib via clinical assessment by CTCAE v5.0 guidelines for adverse event(s)

  Safety Profile

  56 days post commencement of investigational product.

• Percentage of participants that complete the 56-day treatment period.

  56 days post commencement of investigational product.

Secondary Outcomes (2)

• To determine the effect of neo-adjuvant Darovasertib on tumour size in uveal melanoma as measured by ocular ultrasound.

  56 days

• To explore time to recurrence/disease-specific survival in patients on adjuvant Darovasertib assessed by standard of care imaging measured using RECIST 1.1.

  5 years

Study Arms (1)

Intervention

EXPERIMENTAL

Darovasertib 300mg bd

Drug: Darovasertib

Interventions

Darovasertib DRUG

Oral Darovasertib 300 mg tablets twice daily

Intervention

Eligibility Criteria

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

You may qualify if:

• Patient must be at least 18 years of age.
• Primary diagnosis of uveal melanoma as clinically determined by the treating investigator planned for enucleation (prior plaque brachytherapy is permitted)
• Patient is able to provide written, informed consent before initiation of any study related-procedures, and is able, in the opinion of the investigator, to comply with all the requirements of the study.
• Life expectancy \> 3 months.
• Able to safely swallow orally administered medication.
• Patients with a prior history of or clinically stable concurrent malignancy are eligible for enrolment provided the malignancy is clinically insignificant, no treatment is required, and the patient is clinically stable
• Patients with a history of squamous or basal cell carcinoma of the skin or carcinoma in the situ of the cervix may be enrolled.
• Patients with prostate cancer with an elevated PSA not requiring treatment may be enrolled
• Patient has Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 (Karnofsky = 70%).
• Patient has adequate organ function at screening:
• Absolute neutrophil count = 1500/mm3 without the use of hematopoietic growth factors
• Platelet count = 75,000/mm3 (must be at least 2 weeks post-platelet transfusion and not receiving platelet-stimulating agents)
• Haemoglobin = 8.0 g/dL (must be at least 2 weeks post-red blood cell transfusion and not receiving erythropoietic-stimulating agents)
• Total bilirubin = 1.5 x the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x ULN in the absence of documented liver metastases

You may not qualify if:

• Previous treatment with a PKC inhibitor
• Have AEs from prior anti-cancer therapy that have not resolved to Grade =1 except for alopecia, prior peripheral neuropathy, or anaemia. Endocrinopathies resulting from previous immunotherapy are considered part of the medical history and not an AE.
• Untreated or symptomatic malignant lesions in the central nervous system (CNS).
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) - related illness.
• Active infection requiring therapy (except nail fungus), positive tests for Hepatitis B surface antigen (HBsAg) with detected Hepatitis B virus (HBV) DNA or positive Hepatitis C antibody with detected Hepatitis C virus (HCV) RNA.
• Prior gastrectomy or upper bowel removal or any other gastrointestinal disorder or defect e.g., malabsorption disorder such as Crohn's disease or ulcerative colitis, that would interfere with absorption of Darovasertib.
• Patients who are receiving treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following (see Appendix 4):
• known to be strong inducers or inhibitors of CYP3A4/5
• known to be substrates of CYP3A4/5, OAT3, OATP1B1, and MATE1/2-Kwith a narrow therapeutic index
• Females who are pregnant or breastfeeding:
• Women of childbearing potential must not be considering getting pregnant during the study.
• Patients of reproductive potential (male \& female) must practice an effective method of contraception during treatment and for 30 days following the last dose of Darovasertib. Patients unwilling to do so will be excluded.
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of ventricular tachyarrhythmia
• Angina pectoris or acute myocardial infarction = 6 months prior to starting study drug

Sponsors & Collaborators

• St Vincent's Hospital, Sydney: lead

Study Sites (2)

Kinghorn Cancer Centre, St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Uveal Melanoma

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Officials

• Anthony Joshua, FRACP, MBBS, PhD

  St Vincent's Hospital, Sydney

  PRINCIPAL INVESTIGATOR

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: Head of Medical Oncology

Study Record Dates

• First Submitted: December 9, 2021
• First Posted: January 12, 2022
• Study Start: May 3, 2022
• Primary Completion: January 1, 2025
• Study Completion: November 1, 2025
• Last Updated: April 23, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)