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Study of Immunotherapy Plus ADI-PEG 20 for the Treatment of Advanced Uveal Melanoma

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ClinicalTrials.gov Identifier: NCT03922880
Recruitment Status : Recruiting
First Posted : April 22, 2019
Last Update Posted : April 26, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Uveal Melanoma Drug: ADI PEG20 Drug: Nivolumab Drug: Ipilimumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study Combining Arginine Depletion and Checkpoint Inhibition in Uveal Melanomas
Actual Study Start Date : April 16, 2019
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020


Arm Intervention/treatment
Experimental: Advanced Uveal Melanoma Drug: ADI PEG20
ADI-PEG 20 will be administered at a dose of 36mg/m2 intramuscularly once a week.

Drug: Nivolumab
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.

Drug: Ipilimumab
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.




Primary Outcome Measures :
  1. Safety as assessed by CTCAE version 5.0 [ Time Frame: Up to 3 years ]

Secondary Outcome Measures :
  1. Objective Response Rate by RECIST 1.1 [ Time Frame: Up to 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 </= 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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03922880


Contacts
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Contact: Alexander Shoushtari, MD 646-888-4161 shoushta@mskcc.org
Contact: Jedd Wolchok, MD, PhD 646-888-4315 wolchokj@mskcc.org

Locations
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United States, New York
Memorial Sloan - Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Alexander Shoushtari, MD    646-888-4161      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Alexander Shoushtari, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03922880     History of Changes
Other Study ID Numbers: 19-010
First Posted: April 22, 2019    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: • Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
ADI-PEG 20
nivolumab
ipilimumab
19-010
Memorial Sloan Kettering Cancer Center

Additional relevant MeSH terms:
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Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents