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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06121180




Registration number
NCT06121180
Ethics application status
Date submitted
2/11/2023
Date registered
7/11/2023

Titles & IDs
Public title
Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma
Scientific title
A Phase II Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma
Secondary ID [1] 0 0
R2810-ONC-2128
Secondary ID [2] 0 0
MCC-21341
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Uveal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Other cancer types
Eye 0 0 0 0
Diseases / disorders of the eye

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

Experimental: Cemiplimab + Ziv-Aflibercept - One cycle consists of 3 weeks during which:

Cemiplimab 350 mg administered IV every 3 weeks given with Ziv-Aflibercept 4 mg/kg administered IV every 2 weeks.


Treatment: Drugs: ZIV-Aflibercept
Ziv-Aflibercept is an investigational or experimental anti-cancer agent inactivates vascular endothelial growth factor (VEGF) from functioning and scientific experiments have shown that when VEGF is prevented from working, new blood vessels don't form in tumors and these tumors do not grow. In addition, VEGF has been shown to have a negative effect on the immune response and blocking it may help the immune response against cancer.

Treatment: Drugs: Cemiplimab
Cemiplimab is a human monoclonal anti-PD-1 antibody that works by blocking the programmed death-1 (PD-1), a cell receptor on immune cells that is involved in preventing immune cells from destroying other cells.

Blocking the receptor is expected to help immune cells attack cancer cells.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
objective response rate (ORR)
Timepoint [1] 0 0
5 years
Secondary outcome [1] 0 0
Progression free survival (PFS)
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
5 years

Eligibility
Key inclusion criteria
* Provision of signed and dated informed consent form.
* Male or female, aged >/= 18 years old.
* Life expectancy of greater than 3 months in the opinion of the investigator.
* Must be willing and able to provide informed consent signed by study patient or legally acceptable representative, as specified by health authorities and institutional guidelines.
* Patients must have metastatic uveal melanoma, either initial presentation or recurrent, that is histologically diagnosed.
* Patients must have ECOG performance status of 0-1.
* Patients must have measurable disease, according to RECIST version 1.1.
* Patients must have normal organ and marrow function as defined in protocol.
* Urine protein should be screened by urinalysis for Urine Protein Creatinine Ratio (UPCR). For UPCR > 1, a 24-hour urine protein should be obtained, and the level should be <500 mg.
* An echocardiogram should be performed at baseline in all patients. Ejection fraction (EF) from baseline echocardiogram must be within the institutional limits of normal as determined by the reading cardiologist.
* Patients on full-dose anticoagulants (e.g., warfarin) with PT INR >1.5 are eligible provided that both of the following criteria are met:

1. The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin.
2. The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
* A patient may be treatment naïve. However, prior systemic treatments for metastatic uveal melanoma are allowed. There is no limit on the number of prior regimens for metastatic uveal melanoma. However, no prior therapy with bevacizumab, aflibercept or cemiplimab.
* Patients must be free of active brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to enrollment. If known to have prior brain metastases, these must have been adequately managed with standard of care radiation therapy, stereotactic radiosurgery or surgery prior to registration on the study.
* For Women of childbearing potential: use of highly effective contraception for at least 2 or more menstrual cycles prior to screening and agreement to use such a method during study participation and for at least 180 days after the end of study drugs administration.
* For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner For at least 1 month prior to screening and agreement to use such a method during study participation and for at least 180 days after the end of study drugs administration.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnancy or lactation.
* Treatment with another investigational drug or other systemic intervention for uveal melanoma within 4 weeks of initiation of study drugs. Patients must not have radiotherapy within the preceding 4 weeks.

Patients must have recovered from adverse events due to agents administered more than 4 weeks earlier.

* Patients must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery and be free of significant detectable infection.
* Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids. A history of occasional (but not continuous) use of steroid inhalers is allowed.

Replacement doses of steroids for patients with adrenal insufficiency are allowed. Patients who discontinue use of these classes of medication for at least 2 weeks prior to enrollment are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study.

* Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis); other central nervous system autoimmune disease (e.g., poliomyelitis, Multiple sclerosis).
* Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab/placebo. NOTE: Patients who require brief course of steroids (eg, prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded. People taking steroids for physiologic replacement (ie, adrenal insufficiency) are NOT excluded.
* Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.
* Patients who have permanently discontinued anti-cancer immune modulating therapies due to drug related toxicity.
* Encephalitis, meningitis, or uncontrolled seizures in the year prior to screening/enrollment.
* History of immune related pneumonitis within the last 5 years.
* History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved =6 months prior to the enrollment date.
* Patients with a history of solid organ transplant (patients with prior corneal transplant(s) are not excluded).
* Patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible.
* Patients must not have a history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed).
* Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of cemiplimab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
* Patients must not have an active infection requiring current treatment with parenteral antibiotics.
* Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias, or unstable angina.
* Central nervous system: No history of cerebrovascular accident or transient ischemic attacks within the past 6 months.
* Serious or non-healing wound, ulcer, or bone fracture.
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks of initiating study treatment.
* Patients with the following invasive procedures:

* Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks of Day 1 of study therapy.
* Anticipation of need for major surgical procedures during the course of the study.
* Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1 of study therapy. Central venous catheter placements are permitted to be completed 7 or more days prior to Day 1 of study therapy. However, peripherally inserted central catheter (PICC or PIC line) may be placed at any time prior to or during study therapy.
* Patients with clinically significant cardiovascular or cerebrovascular disease:

* History of cerebrovascular accident or transient ischemic attack within past 6 months
* Uncontrolled hypertension, defined as blood pressure >150/100 mm Hg or systolic BP >180 mm Hg if diastolic blood pressure <90 mm Hg, on at least 2 repeated determinations on separate days within past 3 months.
* Myocardial infarction, coronary artery bypass grafting (CABG) or unstable angina within the past 6 Months.
* New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months.
* Clinically significant peripheral vascular disease within past 6 months.
* Pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within past 6 months.
* History of tumor-related or other serious hemorrhage, bleeding diathesis, or underlying coagulopathy.
* PT INR >1.5 unless the patient is on full-dose warfarin.
* Patients who have other current malignancies are not eligible. Patients with other malignancies are eligible if they have been continuously disease free for > 3 years prior to the time of enrollment. Patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ are eligible. Patients with prior history of basal or squamous skin cancer are eligible. Patients who have had multiple primary melanomas are eligible.
* Receipt of a live vaccine within 28 days of the enrollment date.
* Women of childbearing potential or sexually active men, who are unwilling to practice highly effective contraception for at least 2 or more menstrual cycles (women) or 1 month (men) prior to screening, during the study, and for at least 180 days after the last dose of study drug(s).

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/02/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/10/2030
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida

Funding & Sponsors
Primary sponsor type
Other
Name
H. Lee Moffitt Cancer Center and Research Institute
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Genzyme, a Sanofi Company
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Regeneron Pharmaceuticals
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Ahmad Tarhini, MD, PHD
Address 0 0
Moffitt Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Malik Hall
Address 0 0
Country 0 0
Phone 0 0
813-745-5170
Fax 0 0
Email 0 0
Malik.Hall@moffitt.org
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


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/NCT06121180