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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05187884




Registration number
NCT05187884
Ethics application status
Date submitted
9/12/2021
Date registered
12/01/2022

Titles & IDs
Public title
Neoadjuvant/Adjuvant Trial of Darovasertib in Ocular Melanoma
Scientific title
Neoadjuvant/Adjuvant Trial of Darovasertib in Ocular Melanoma
Secondary ID [1] 0 0
NADOM
Universal Trial Number (UTN)
Trial acronym
NADOM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ocular Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Darovasertib

Experimental: Intervention - Darovasertib 300mg bd


Treatment: Drugs: Darovasertib
Oral Darovasertib 300 mg tablets twice daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
56 days post commencement of investigational product.
Primary outcome [2] 0 0
Percentage of participants that complete the 56-day treatment period.
Timepoint [2] 0 0
56 days post commencement of investigational product.
Secondary outcome [1] 0 0
To determine the effect of neo-adjuvant Darovasertib on tumour size in uveal melanoma as measured by ocular ultrasound.
Timepoint [1] 0 0
56 days
Secondary outcome [2] 0 0
To explore time to recurrence/disease-specific survival in patients on adjuvant Darovasertib assessed by standard of care imaging measured using RECIST 1.1.
Timepoint [2] 0 0
5 years

Eligibility
Key inclusion criteria
* 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
* Serum albumin = 30 umol/L
* Creatinine Clearance = 60 mL/min/1.73 m2 by Cockroft-Gault equation [Appendix 6]
* Prothrombin time/International Normalized Ratio (INR) or partial thromboplastin time test results at screening = 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose for at least 4 weeks prior to the first dose of study drug).
* Female patients of childbearing potential must be non-pregnant, non-lactating, and have a negative serum human chorionic gonadotropin pregnancy test result within 28 days prior to the first study drug administration.

* Females of childbearing potential who are sexually active with a non-sterilized male partner agree to use effective methods of contraception from screening, throughout the study drug and agree to continue using such precautions for 30 days after the final dose of study drug.
* Non-sterilized males who are sexually active with a female of childbearing potential must agree to use effective methods of contraception from Day 1 throughout the study drug and for 30 days after the final dose of study drug.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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
* Presence of unstable atrial fibrillation (ventricular response > 100 BPM); patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria
* Angina pectoris or acute myocardial infarction = 6 months prior to starting study drug
* Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
* Patients with a drug eluting stent for cardiovascular purposes placed = 6 months prior to starting study drug
* Corrected QT interval using Fridericia's method (QTcF) > 480 msec on baseline ECG (mean of baseline values). If electrolytes are abnormal, they may be corrected, and baseline ECGs should be repeated (Appendix 5).
* Known to have previously received Darovasertib
* Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2025
Actual
Sample size
Target
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre, St. Vincent's Hospital - Sydney
Recruitment hospital [2] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Anthony Joshua, FRACP
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
St Vincent's Hospital, Sydney
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anthony Joshua, FRACP, MBBS, PhD
Address 0 0
St Vincent's Hospital, Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No Plan to share participant data with individuals outside this trial


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05187884