Brief Title
Study of Immunotherapy Plus ADI-PEG 20 for the Treatment of Advanced Uveal Melanoma
Official Title
Pilot Study Combining Arginine Depletion and Checkpoint Inhibition in Uveal Melanomas
Brief Summary
This study is measuring the safety of the study drug, ADI-PEG 20, combined with immunotherapy
drugs nivolumab and ipilimumab in treating patients with advanced uveal melanoma.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Safety as assessed by CTCAE version 5.0
Secondary Outcome
Objective Response Rate by RECIST 1.1
Condition
Uveal Melanoma
Intervention
ADI PEG20
Study Arms / Comparison Groups
Advanced Uveal Melanoma
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
9
Start Date
April 16, 2019
Completion Date
April 2022
Primary Completion Date
April 2022
Eligibility Criteria
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 /= 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Alexander Shoushtari, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03922880
Organization ID
19-010
Responsible Party
Sponsor
Study Sponsor
Memorial Sloan Kettering Cancer Center
Study Sponsor
Alexander Shoushtari, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center
Verification Date
January 2021