Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
MY TRIALS
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Register a trial
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06151236
Registration number
NCT06151236
Ethics application status
Date submitted
21/11/2023
Date registered
30/11/2023
Titles & IDs
Public title
Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma
Query!
Scientific title
A Phase 2, Open Label, Single Arm Clinical Trial of Neoadjuvant Nivolumab and Relatlimab in Stage I To III Resectable Merkel Cell Carcinoma
Query!
Secondary ID [1]
0
0
CA224-1064
Query!
Secondary ID [2]
0
0
MIA2023/489
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Merkel Cell Carcinoma
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Malignant melanoma
Query!
Cancer
0
0
0
0
Query!
Non melanoma skin cancer
Query!
Cancer
0
0
0
0
Query!
Kidney
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
Experimental: Neoadjuvant Treatment - Nivolumab and relatlimab will be administered in a fixed dose combination (FDC). The FDC product contains nivolumab and relatlimab in a protein-mass ratio of 3:1 (nivolumab 240 mg and relatlimab 80 mg): in a 20 mL concentrate solution per single vial. The dose and dosing regimen for this study is nivolumab 480 mg and relatlimab 160 mg - 2 vials per infusion. This was primarily based on the observed benefit/risk profile observed in metastatic melanoma patients from Study CA224-020 pharmacokinetics (PK), pharmacodynamics, and extensive nivolumab monotherapy clinical experience. In addition, the Phase 2/3 Study CA224-047 established this dose as active in unresectable and metastatic melanoma.
This study is open label and single arm, with all patients scheduled to receive two doses of nivolumab and relatlimab FDC prior to surgery on days 1 and 29.
Treatment: Drugs: Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
Dual inhibition of the distinct LAG3 and PD-1 checkpoint pathways
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Pathological complete response rate
Query!
Assessment method [1]
0
0
Proportion of patients with a pathological complete response, as determined on the week 6 surgical specimen using the guidelines published by the International Neoadjuvant Melanoma Consortium: Complete pathological response (pCR) = 0% viable tumour cells in the surgical specimen
Query!
Timepoint [1]
0
0
Week 6
Query!
Secondary outcome [1]
0
0
Pathological non-complete response rate to neoadjuvant immunotherapy
Query!
Assessment method [1]
0
0
Proportion of patients with each non-pCR response category, as determined on the week 6 surgical specimen using the guidelines published by the International Neoadjuvant Melanoma Consortium:
* Near complete pathological response - (near pCR) - \>0% - =10% viable tumour
* Partial pathological response (pPR) - \>10 - =50% viable tumour
* Non pathological response (pNR) - \>50% viable tumour
Query!
Timepoint [1]
0
0
Week 6
Query!
Secondary outcome [2]
0
0
Toxicity and tolerability of neoadjuvant immunotherapy and surgery
Query!
Assessment method [2]
0
0
The proportion of patients with adverse events (AE) as described in CTCAE version 5.0, from the initiation of study treatment until at least 135 days after the end of treatment. Outcome measures include the proportion of patients with:
* An AE by CTCAE term and grade and duration
* AEs attributable to neoadjuvant study treatment
* Grade 3/4/5 AEs by AE term
* A requirement to interrupt study treatment and/or delay surgery within time limit due to an AE
* A requirement to discontinue study treatment early due to an AE
* A requirement for oral or parenteral steroid treatment for immune-related adverse events.
* Post-operative complications (e.g. seroma formation, wound infection or lymphoedema) and duration of events.
* and the Surgeon's assessment of 'operability' from baseline and at surgery.
Query!
Timepoint [2]
0
0
Week 24
Query!
Secondary outcome [3]
0
0
Objective response rate to neoadjuvant immunotherapy
Query!
Assessment method [3]
0
0
The proportion of patients within each response category, as assessed using RECIST version 1.1, comparing week 6 to baseline CT and MRI.
Objective response rate= CR and PR
Query!
Timepoint [3]
0
0
Week 6
Query!
Secondary outcome [4]
0
0
Metabolic response rate to neoadjuvant immunotherapy
Query!
Assessment method [4]
0
0
The proportion of patients within each response category, as assessed using PERCIST (standardised uptake value \[SUV\]) comparing week 6 to baseline PET.
Metabolic response rate = CMR and PMR.
Query!
Timepoint [4]
0
0
Week 6
Query!
Secondary outcome [5]
0
0
Recurrence-free survival
Query!
Assessment method [5]
0
0
The proportion of patients alive and disease free from the time of surgery
Query!
Timepoint [5]
0
0
10 years
Query!
Secondary outcome [6]
0
0
Disease progression rate
Query!
Assessment method [6]
0
0
1. The proportion of patients alive and with RECIST-defined progression of disease from the date of consent to the first radiographical evidence of local, regional or distant progression.
2. Disease progression which leads to unresectable MCC.
Query!
Timepoint [6]
0
0
Week 6
Query!
Secondary outcome [7]
0
0
Event-free survival rate
Query!
Assessment method [7]
0
0
The proportion of patients alive and disease free from the date of consent to the first radiographical evidence of local, regional or distant progression
Query!
Timepoint [7]
0
0
10 years
Query!
Secondary outcome [8]
0
0
Overall survival rate
Query!
Assessment method [8]
0
0
The proportion of patients alive at years 1, 2, 5 and 10, and to actual date of death (in months), from the initiation of study treatment.
Query!
Timepoint [8]
0
0
10 years
Query!
Secondary outcome [9]
0
0
Patient reported quality of life
Query!
Assessment method [9]
0
0
1. Changes in patient rated quality of life scores using QLQ-C30 and EQ-5D-5L from date of consent to 6 -12 weekly intervals until the end of year 1.
2. The correlation of patient-rated quality of life scores with adverse events.
Query!
Timepoint [9]
0
0
1 year
Query!
Secondary outcome [10]
0
0
Study treatment completion rate
Query!
Assessment method [10]
0
0
1. Proportion of patients receiving full neoadjuvant drug treatment per schedule and number of treatments missed.
2. Proportion of patients undergoing planned surgery at week 6.
3. Reasons for incomplete study treatment e.g. adverse event, withdrawn consent, , disease progression, patient lost to follow-up.
Query!
Timepoint [10]
0
0
Week 8
Query!
Eligibility
Key inclusion criteria
* Aged = 18 years
* Written consent Histologically confirmed, resectable Merkel cell carcinoma with AJCC (8th ed) clinical stage I (= 10 mm), II, or III
* In-transit metastases are permitted if they are completely resectable
* Measurable disease according to RECIST 1.1 criteria
* Tumour amenable to core biopsy
* Previous radiotherapy permitted if there is RECIST-measurable progression of disease since the completion of radiotherapy
* ECOG 0-1
* Adequate organ function on blood pathology
* Life expectancy >12 months
* Female patients to use effective contraception during study treatment and for 5 months after last dose.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Clinical or radiographic evidence of distant metastases
* Contraindication to nivolumab and / or relatlimab
* Prior anti-PD-1, CTLA-4, PDL-1 or LAG 3 antibody exposure, or an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease or any chemotherapy or experimental local or systemic drug treatment
* Active autoimmune disease or requirement for chronic steroid therapy other than hormone replacement therapy
* A diagnosis of immunodeficiency or chronic steroid therapy >10 mg OD prednisone or equivalent
* Additional malignancy active within past 3 years; patients with chronic lymphocytic leukaemia can be included in this study.
* Uncontrolled cardiovascular disease or history of myocarditis - Has had an allogenic tissue/solid organ transplant
* Active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
* Known HIV
* Pregnant or breast feeding females
* Concurrent medical or social conditions that may prevent the patient attending assessments or procedures per schedule
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
NA
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Single group
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
11/03/2024
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
1/04/2034
Query!
Actual
Query!
Sample size
Target
20
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Melanoma Institute Australia - Wollstonecraft
Query!
Recruitment postcode(s) [1]
0
0
2065 - Wollstonecraft
Query!
Funding & Sponsors
Primary sponsor type
Other
Query!
Name
Melanoma Institute Australia
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/industry
Query!
Name [1]
0
0
Bristol-Myers Squibb
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The goal of this clinical trial is to test neoadjuvant dual immunotherapy in Merkel cell carcinoma with the aim to improve recurrence-free survival
Query!
Trial website
https://clinicaltrials.gov/study/NCT06151236
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Ines Esteves Domingues Pires da Silva
Query!
Address
0
0
Melanoma Instiute Australia
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Monica Osorio
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
+ 61 2 9911 7296
Query!
Fax
0
0
Query!
Email
0
0
[email protected]
Query!
Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Query!
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/NCT06151236