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/NCT04261855




Registration number
NCT04261855
Ethics application status
Date submitted
6/02/2020
Date registered
10/02/2020
Date last updated
28/10/2020

Titles & IDs
Public title
Targeted Therapy and Avelumab in Merkel Cell Carcinoma
Scientific title
A Phase Ib/II Study of Combination Avelumab With Peptide Receptor Radionuclide Therapy or Conventional Fractionated Radiotherapy in Patients With Metastatic Merkel Cell Carcinoma
Secondary ID [1] 0 0
10.17
Universal Trial Number (UTN)
Trial acronym
GoTHAM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Merkel Cell Carcinoma 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab
Treatment: Other - External Beam Radiation Therapy (EBRT)
Treatment: Other - Lutetium-177 (177Lu)-DOTATATE

Experimental: Arm A - Avelumab plus External Beam Radiation Therapy (EBRT)

Experimental: Arm B - Avelumab plus External Beam Radiation Therapy (EBRT)

Experimental: Arm C - Avelumab plus Lutetium-177 (177Lu)-DOTATATE


Treatment: Drugs: Avelumab
All patients will receive avelumab intravenously (IV) at 10 mg/kg every 2 weeks for 24 months or until unacceptable toxicity or evidence of disease progression

Treatment: Other: External Beam Radiation Therapy (EBRT)
Patients registered to Arm A or randomised to Arm B will receive EBRT on 2 occasions, 8-10 weeks apart

Treatment: Other: Lutetium-177 (177Lu)-DOTATATE
Patients randomised to Arm C will receive 177-Lu-DOTATATE treatment on 2 occasions, 8-10 weeks apart

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) at 12 months - To evaluate the anti-tumour activity as reflected by PFS rate at 12 months. PFS is defined as the time from treatment initiation until the first date of documented radiographic progression or death due to any cause, whichever occurs first. The radiographic progression will be assessed by the Investigator according to RECIST v1.1.
Timepoint [1] 0 0
3 years
Secondary outcome [1] 0 0
Progression Free Survival (PFS) at 24 months - Time to disease progression including rate at specific landmark timepoint of 24 months.
Timepoint [1] 0 0
4 years
Secondary outcome [2] 0 0
Overall Survival (OS) at 12 and 24 months - 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 [2] 0 0
4 years
Secondary outcome [3] 0 0
Best Objective Response Rate (ORR) according to RECIST v1.1 - To evaluate best ORR according to response evaluation criteria in solid tumours version 1.1 (RECIST v1.1). ORR is defined as PR or CR at any stage from time of treatment initiation according to RECIST v1.1.
Timepoint [3] 0 0
4 years
Secondary outcome [4] 0 0
The safety and tolerability of 177Lu-DOTATATE or EBRT in combination with avelumab. - Rate of treatment-related adverse events (AEs). Safety will be measured by serious adverse events (SAEs) and AEs assessed using the NCI CTCAE v5.0.
Timepoint [4] 0 0
4 years
Secondary outcome [5] 0 0
Rate of treatment discontinuation due to toxicity - This is defined as the proportion of patients who discontinue with treatment due to treatment-related toxicity.
Timepoint [5] 0 0
4 years

Eligibility
Key inclusion criteria
- Patient is 18 years of age or older and who has provided written informed consent.

- Patient has histologically confirmed metastatic MCC.

- Eastern Cooperative Oncology Group (ECOG) performance status of =2 .

- Willing and able to comply with all study protocol requirements for the duration of
the study.

- Patient must have measurable disease by CT or MRI per RECIST version 1.1 criteria.

- Patient is treatment naïve (no prior systemic therapy for unresectable or metastatic
MCC). Note that prior chemotherapy is permitted in the adjuvant setting for
loco-regional disease. Prior radiation is permitted for treatment of the primary or
loco-regional disease.

- At least 2 weeks since the completion of prior therapy, including surgery or
radiotherapy.

- Screening laboratory values, obtained within 14 days prior to
registration/randomisation must meet the criteria specified in the protocol.

- Women of childbearing potential (WOCBP) must use appropriate method(s) of
contraception

- WOCBP must have a negative serum or urine pregnancy test within within 7 days prior to
the start of avelumab treatment and should be performed every 4 weeks in line with
other safety bloods or clinical reviews.

- Male patients who are sexually active with a WOCBP must use any contraceptive method
with a failure rate of less than 1% per year.

- Patient must be agreeable to have archival tumour material collected
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient is excluded if they have ever had any brain or leptomeningeal metastases.

- Prior exposure to immune checkpoint inhibitors (e.g. anti-CTLA-4,
anti-PD-1/PD-L1/PD-L2, etc.) or any other antibody or drug specifically targeting
T-cell co-stimulation or immune checkpoint pathways.

- Prior exposure to 177Lu-DOTATATE.

- Prior malignancy within the previous 2 years, except for locally curable cancers that
have been apparently cured (e.g. basal or squamous cell skin cancer, superficial
bladder cancer or carcinoma in situ of the cervix, colon, bladder or breast).

- Life expectancy of 6 months or less.

- An active, known or suspected autoimmune disease that might deteriorate when receiving
an immunostimulatory agent. Patients are permitted to enrol if they have vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger.

- Current use of immunosuppressive medication, with exceptions detailed in the protocol

- Prior organ transplantation, including allogeneic stem-cell transplantation.

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

- Positive test for hepatitis B virus (HBV) surface antigen and/or confirmatory
hepatitis C virus (HCV) RNA (if anti-HCV antibody tested positive at Screening).

- Pregnant or breastfeeding.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Patients should be excluded if they have a condition requiring systemic treatment with
either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days of study drug administration.

- Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade > 1); however,
alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety
risk based on Investigator's judgement are acceptable.

- Known prior severe hypersensitivity to investigational product or any component in its
formulations, including known hypersensitivity reactions to monoclonal antibodies (NCI
CTCAE v5.0 Grade 3).

- Patients with symptomatic or impending cord compression unless appropriately treated
beforehand and clinically stable.

- Use of any live vaccines against infectious diseases (e.g., influenza, varicella,
etc.) within 30 days of registration.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/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
Royal North Shore Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [6] 0 0
Sir Charles Gaidner Hospital - Perth
Recruitment postcode(s) [1] 0 0
2065 - Sydney
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Perth

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

Ethics approval
Ethics application status

Summary
Brief summary
10.17 GoTHAM is intended as a signal-seeking, biomarker, phase Ib/II study that will evaluate
the safety and anti-tumour activities of the novel combination of avelumab with
177-Lu-DOTATATE (a type of peptide receptor radionuclide therapy; PRRT) or external beam
radiation therapy (EBRT) in patients with metastatic Merkel cell carcinoma (mMCC).
Trial website
https://clinicaltrials.gov/show/NCT04261855
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dr Shahneen Sandhu, MBBS, FRACP
Address 0 0
Peter MacCallum Cancer Centre, Australia
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
+610414579120
Fax 0 0
Email 0 0
gotham@masc.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04261855