- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03922880
Study of Immunotherapy Plus ADI-PEG 20 for the Treatment of Advanced Uveal Melanoma
Pilot Study Combining Arginine Depletion and Checkpoint Inhibition in Uveal Melanomas
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Advanced or unresectable melanoma of presumed uveal origin. Non-uveal melanomas with "malignant blue nevus" physiology with GNAQ, GNA11, CYSLTR2, or PLCB4 driver alterations are eligible upon discussion with the Principal Investigator.
- Disease must be measurable according to RECIST 1.1. Disease that has undergone local therapy in the past 30 days is not considered measurable unless the investigator has documented progression despite the local therapy.
- Disease must be amenable to a biopsy attempt, in the opinion of the investigator.
- Asymptomatic untreated brain metastases are allowed. Symptomatic brain metastases that have undergone local therapy with RT or surgery and have not required an increase in steroid dose in prior 2 weeks are allowed.
Note: Seizure prophylaxis with untreated brain metastases are allowed.
- Patients must have an Easter Cooperative Oncology Group (ECOG) Performance Statue (PS) of 0-1.
- Acceptable liver, renal, and hematological function:
- Total bilirubin </= 1.5x upper limit of normal (ULN); patients with Gilbert's Syndrome must have bilirubin </= 3x ULN
- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) </= 3 x ULN (</= 5x if liver metastases are present)
- Estimated glomerular filtration rate (GFR) >/= 30 mL/min using a cancer-specific GFR Model; the calculator found at:
http://tavarelab.cruk.com.ac.uk/JanowitzWilliamsGFR/
- Hemoglobin >/= 9 g/dL
- Neutrophils >/= 1.5 x 10^9/L
- Platelets >/= 100 x 10^9/L
Female patients of childbearing potential and their partners (if male) and male patients with female partners of childbearing potential and their partners must agree to use a highly effective form of contraception for the duration of the study from the list below or agree to refrain from intercourse for the duration of the trial and for at least 30 days after the last administration of ADI-PEG20 and at least 150 days (if female) or 210 days (if male) after the final dose of ipilimumab and/or nivolumab whichever is later. Highly effective forms of contraception include the following:
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal)
- progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- intrauterine device
- intrauterine hormone-releasing system
- bilateral tubal occlusion
- vasectomized partner
Exclusion Criteria:
- Other active malignancy that in the opinion of the treating investigator will interfere with the assessments of efficacy for uveal melanoma in this study
- History of seizure disorder not related to malignancy
- Pregnancy or lactation
- Expected non-adherence to protocol
- Known allergy to E. coli drug products (such as GM-CSF)
- Known allergy to pegylated compounds
- Prior treatment with ADI-PEG20 or another experimental arginine deprivation strategy
- Systemic anticancer therapy within 3 weeks or 1 cycle length, whichever is shorter, of first day of planned study therapy
- Presence of treatment-related adverse events that have not recovered or stabilized at Grade 1 (excepting vitiligo and alopecia or treated endocrine conditions). AEs that are Grade 2 that are not felt to be a significant safety risk (e.g. rash, asymptomatic thyroiditis) may be allowable upon discussion with the Principal Investigator.
- Active autoimmune disease or any condition requiring greater than 10mg prednisone per day equivalent or other immune suppressive medication (e.g. anti-TNF agents) within 14 days of study screening. Inhaled or topical steroids and adrenal replacements does of steroids >10mg prednisone are allowed in the absence of active autoimmune disease.
- History of myocarditis or motor neuropathy of any grade
- Gout flares within the past 28 days or sequelae of chronic gout, such as gouty arthritis, are excluded.
Note: Patients with asymptomatic hyperuricemia without arthralgias or arthritic symptoms are eligible, as are patients with known gout on chronic uric acid lowering medication who have not experienced a flare within 28 days
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Advanced Uveal Melanoma
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ADI-PEG 20 will be administered at a dose of 36mg/m2 intramuscularly once a week.
Nivolumab 240mg + Ipilimumab 1mg/kg for up to 8 total doses of ipilimumab.
One ipilimumab has completed, nivolumab 480mg will be given every 4 weeks.
Ipilimumab 1mg/kg with Nivolumab 240mg for up to 8 total doses of ipilimumab.
The first four doses of ipilimumab will be scheduled once every 3 weeks.
The 5th-8th doses of ipilimumab will be scheduled once every 6 weeks with nivoumab 240mg every 3 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety as assessed by CTCAE version 5.0
Time Frame: Up to 3 years
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Up to 3 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Objective Response Rate by RECIST 1.1
Time Frame: Up to 3 years
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Up to 3 years
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Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Eye Diseases
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Uveal Diseases
- Neuroendocrine Tumors
- Nevi and Melanomas
- Eye Neoplasms
- Melanoma
- Uveal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
- Ipilimumab
Other Study ID Numbers
- 19-010
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Uveal Melanoma
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Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedIris Melanoma | Medium/Large Size Posterior Uveal Melanoma | Stage IIA Uveal Melanoma | Stage IIB Uveal Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal MelanomaUnited States
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National Cancer Institute (NCI)ExelisisCompletedStage IV Uveal Melanoma AJCC v7 | Recurrent Uveal Melanoma | Stage III Uveal Melanoma AJCC v7 | Stage IIIA Uveal Melanoma AJCC v7 | Stage IIIB Uveal Melanoma AJCC v7 | Stage IIIC Uveal Melanoma AJCC v7United States, Canada
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Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI)TerminatedStage IV Uveal Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal MelanomaUnited States
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National Cancer Institute (NCI)CompletedIris Melanoma | Stage IV Uveal Melanoma | Medium/Large Size Posterior Uveal Melanoma | Recurrent Uveal Melanoma | Ocular Melanoma With Extraocular Extension | Small Size Posterior Uveal MelanomaUnited States, Canada
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Alliance for Clinical Trials in OncologyWithdrawnMetastatic Uveal Melanoma | Advanced Uveal Melanoma | Unresectable Uveal Melanoma
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Incyte Corporation; University of VirginiaCompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Mucosal Melanoma | Stage IV Uveal Melanoma | Stage IIIA Skin Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal Melanoma | Recurrent Uveal MelanomaUnited States
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National Cancer Institute (NCI)CompletedStage IV Cutaneous Melanoma AJCC v6 and v7 | Recurrent Melanoma | Stage IIIC Cutaneous Melanoma AJCC v7 | Mucosal Melanoma | Iris Melanoma | Stage IIIA Cutaneous Melanoma AJCC v7 | Stage IIIB Cutaneous Melanoma AJCC v7 | Stage IV Uveal Melanoma AJCC v7 | Medium/Large Size Posterior Uveal Melanoma | Recurrent... and other conditionsUnited States
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National Cancer Institute (NCI)Memorial Sloan Kettering Cancer Center; Institut Curie Paris; Moffitt Cancer...Active, not recruitingMetastatic Uveal Melanoma | Stage IV Uveal Melanoma AJCC v7United States
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National Cancer Institute (NCI)CompletedStage IV Uveal Melanoma AJCC v7 | Recurrent Uveal MelanomaUnited States
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National Cancer Institute (NCI)CompletedStage IV Uveal Melanoma AJCC v7 | Recurrent Uveal MelanomaUnited States, France, United Kingdom
Clinical Trials on ADI PEG20
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Polaris GroupRecruiting
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Polaris GroupRecruitingHepatocellular Carcinoma | Advanced Hepatocellular CarcinomaTaiwan, Vietnam
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Polaris GroupRecruitingSoft Tissue SarcomaUnited States
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Washington University School of MedicineChildren's Discovery Institute; Polaris Pharmaceuticals, Inc.Not yet recruiting
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Chang Gung Memorial HospitalRecruitingHepatocellular CarcinomaTaiwan
-
Polaris GroupTerminated
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Polaris GroupRecruitingGlioblastoma Multiforme (GBM)Taiwan
-
Queen Mary University of LondonHoffmann-La Roche; Polaris GroupWithdrawnCarcinoma, Non-Small-Cell Lung
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Ludwig Institute for Cancer ResearchMemorial Sloan Kettering Cancer Center; NYU Langone HealthCompletedSkin Cancer | Metastatic Melanoma | NeoplasmUnited States
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FDA Office of Orphan Products DevelopmentCompleted