COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

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/show/NCT04291885




Registration number
NCT04291885
Ethics application status
Date submitted
6/02/2020
Date registered
2/03/2020
Date last updated
20/11/2020

Titles & IDs
Public title
Immunotherapy Adjuvant Trial in Patients With Stage I-III Merkel Cell Carcinoma
Scientific title
A Randomised, Placebo-controlled, Phase II Trial of Adjuvant Avelumab in Patients With Stage I-III Merkel Cell Carcinoma
Secondary ID [1] 0 0
03.18
Universal Trial Number (UTN)
Trial acronym
I-MAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Merkel Cell Carcinoma 0 0
Merkel Cell Carcinoma, Stage I 0 0
Merkel Cell Carcinoma, Stage II 0 0
Merkel Cell Carcinoma, Stage III 0 0
Neuroendocrine Tumors 0 0
Carcinoma Neuroendocrine Skin 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

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

Experimental: Avelumab - 6 months of Avelumab at a dose of 800mg as a 60-minute IV infusion once every 2 weeks (13 doses)

Placebo Comparator: Placebo - 6 months of Placebo as a 60-minute IV infusion once every 2 weeks (13 doses)


Treatment: Drugs: Avelumab
Avelumab IV infusion

Treatment: Drugs: Placebo
Placebo IV infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrence-free survival (RFS) - RFS, the primary endpoint, is anticipated to be analysed over an average planned follow-up of 3.5 years per participant. An analysis of RFS at the 24 month time point of follow-up per participant will also be conducted as it is anticipated that the minimum follow-up per patient will be 24 months and the sample size rationale utilises RFS rates at 24 months in historical controls. RFS is defined as the time from treatment initiation until the first date of any signs or symptoms of recurrence of tumour.
Timepoint [1] 0 0
24 Months
Secondary outcome [1] 0 0
Overall survival (OS) - OS rates at specific landmark timepoints of 12 and 24 months. OS is defined as the time from treatment initiation to the date of death due to any cause.
Timepoint [1] 0 0
24 Months
Secondary outcome [2] 0 0
Disease-specific survival (DSS) - DSS is the percentage of participants who have not died from Merkel Cell Carcinoma at 24 months from treatment initiation.
Timepoint [2] 0 0
24 Months
Secondary outcome [3] 0 0
Rate of loco-regional failure free survival (LRFFS) - Rate of loco-regional failure free survival (LRFFS) is defined as the time from treatment initiation to the first recurrence of the loco-regional tumour.
Timepoint [3] 0 0
24 Months
Secondary outcome [4] 0 0
Distant metastasis-free survival (DMFS) - DMFS is defined as the time from treatment initiation to the first evidence of distant metastatic disease.
Timepoint [4] 0 0
24 Months
Secondary outcome [5] 0 0
Treatment toxicity and tolerability as assessed by NCI CTCAE v5.0 - Rate of treatment-related adverse events (AEs). Safety will be measured by serious adverse events (SAEs) and AEs assessed as per NCI CTCAE v5.0, including immune-related adverse events.
Timepoint [5] 0 0
24 Months
Secondary outcome [6] 0 0
Patient-reported quality of life (QoL) as assessed by FACT-M questionnaire - FACT-M form (version 4) will be utilised. This will include patient-reported questions relating to physical wellbeing, social/family wellbeing, emotional wellbeing, functional wellbeing and additional patient concerns which are measured from 0-4 (Not at all - Very Much).
Timepoint [6] 0 0
24 Months

Eligibility
Key inclusion criteria
1. Histologically confirmed Merkel cell carcinoma (MCC) which is either:

- clinical stage I (pathological stage I MCC patients are not eligible for the
study);

- clinical or pathological stage II (including IIA and IIB);

- clinical or pathological stage III (including IIIA and IIIB).

2. Absence of distant metastatic disease on baseline 18-Fludeoxyglucose (18FDG) -
Positron Emission Tomography (PET) / Computed Tomography (CT) scan.

3. 18 years of age or older.

4. Eastern Cooperative Oncology Group (ECOG) of 0 - 2.

5. Willing and able to provide written informed consent and comply with all study
requirements.

6. Adequate haematological, liver and renal function as determined by the screening
laboratory values outlined in the protocol obtained within 14 days prior to
randomisation

7. Agreeable to collection of archival tumour material. Where possible, the most recently
acquired tumour specimen should be provided.

8. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy
test within 72 hours prior to the start of treatment
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that
required treatment with systemic immunosuppressive treatments, which may suggest
significant risk for immune-related adverse events.

2. Prior treatment with an agent that blocks the PD-1/PD-L1 pathway.

3. Previous cancer immunotherapy, specifically interferon, anti-CD137, or anti-CTLA-4
antibody or any other antibody or drug specifically targeting T cell co-stimulation or
checkpoint pathways are not permitted.

4. Prior treatment with other immune-modulating agents that was within fewer than 28 days
prior to the first dose of Avelumab.

5. Active infection requiring antibiotics within 7 days of study entry.

6. Active tuberculosis.

7. Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).

8. Uncontrolled infection with hepatitis B or hepatitis C virus (HBV or HCV) infection;
Patients with previously successfully treated HCV, with positive anti-HCV antibody but
undetectable (HCV) ribonucleic acid (RNA) levels are allowed on trial.

9. Current use of immunosuppressive medication, except for the following: a. intranasal,
inhaled, topical steroids, or local steroid injection ; b. systemic corticosteroids at
physiologic doses = 10 mg/day of prednisone or equivalent; c. steroids as
premedication for hypersensitivity reactions

10. Any systemic anti-cancer treatment (chemotherapy, targeted systemic therapy)
investigational or standard of care, within 28 days of the first dose of Avelumab or
planned to occur during the study period. Patients receiving bisphosphonates or
denosumab will not be excluded.

11. Pregnant or breastfeeding.

12. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organising pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organising pneumonia), or evidence of active pneumonitis on screening chest CT scan).

13. Uncontrolled cardiac disease including not limited to symptomatic congestive heart
failure, unstable angina pectoris, life-threatening cardiac arrhythmia

14. Known prior severe hypersensitivity to investigational product or any component in its
formulations, including known severe hypersensitivity reactions to monoclonal
antibodies (NCI CTCAE v5 Grade 3).

15. Use of live attenuated vaccines within 28 days of first dose of Avelumab.

16. Any acute or chronic psychiatric problems that, in the opinion of the Investigator,
make the patient ineligible for participation due to compliance concerns.

17. Patients with prior allogeneic stem cell or solid organ transplantation.

18. Patients who are involuntarily incarcerated.

19. No evidence of other malignancy in the past 3 years, with exception of tumours with
negligible risk of metastasis or death.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [2] 0 0
Melanoma Institute Australia - Sydney
Recruitment hospital [3] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [4] 0 0
Westmead Hospital - Sydney
Recruitment hospital [5] 0 0
Calvary Mater Hospital - Sydney
Recruitment hospital [6] 0 0
Royal Brisbane and Woman's Hospital - Brisbane
Recruitment hospital [7] 0 0
Townsville Hospital - Townsville
Recruitment hospital [8] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [9] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [11] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [12] 0 0
Affinity Oncology - Perth
Recruitment postcode(s) [1] 0 0
2050 - Sydney
Recruitment postcode(s) [2] 0 0
2065 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Sydney
Recruitment postcode(s) [4] 0 0
2298 - Sydney
Recruitment postcode(s) [5] 0 0
4029 - Brisbane
Recruitment postcode(s) [6] 0 0
- Townsville
Recruitment postcode(s) [7] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 0 0
5000 - Adelaide
Recruitment postcode(s) [9] 0 0
3000 - Melbourne
Recruitment postcode(s) [10] 0 0
6150 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma and Skin Cancer Trials Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The I-MAT trial is a phase II randomised and placebo-controlled trial for patients with stage
I-III Merkel cell carcinoma (MCC) to explore efficacy and tolerability of avelumab as
adjuvant immunotherapy.
Trial website
https://clinicaltrials.gov/show/NCT04291885
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Wen Xu, MBBS, FRACP
Address 0 0
Princess Alexandra Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Narelle Williams
Address 0 0
Country 0 0
Phone 0 0
+61414579120
Fax 0 0
Email 0 0
imat@masc.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04291885