Summary

for people ages 18 years and up (full criteria)
healthy people welcome
at San Francisco, California and other locations
study started
estimated completion
Katy Tsai

Description

Summary

This is an open-label, multi-site, single-arm Phase 2 study of adjuvant nivolumab combined with ipilimumab for the treatment of adult subjects with completely treated high-risk ocular melanoma, as defined in eligibility criteria, without evidence of metastatic disease. All patients enrolled to the study will be treated with nivolumab 240 mg IV every 2 weeks plus ipilimumab 1mg/kg IV every 6 weeks. 1 cycle = 6 weeks. Treatment will continue until disease progression, unacceptable toxicity, patient request to discontinue or completion of treatment. Subjects may receive up to 25 doses of nivolumab and 8 doses of ipilimumab

Official Title

Phase II Single-arm Multi-center Study of Adjuvant Ipilimumab in Combination With Nivolumab in Subjects With High-risk Ocular Melanoma

Keywords

Melanoma Nivolumab Ipilimumab Nivolumab and Ipilimumab

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  2. Age ≥ 18 years at the time of consent. No dosing or adverse event data are currently available on the use of ipilimumab in combination with nivolumab in patients < 18 years of age.
  3. ECOG Performance Status of 0-1 within 28 days prior to registration.
  4. Patients must have clinically confirmed ocular melanoma diagnosed by a retinal specialist or ocular oncologist. NOTE: Patients with cutaneous melanoma, acral melanoma, mucosal melanoma, or conjunctival melanoma are ineligible.
  5. Patients must have ocular melanoma that is considered high-risk for recurrence as defined by one of the following criteria:
  6. Gene Expression Profile using 15-gene panel (Castle Bioscience) and be classified as Class 2, or
  7. 3-year recurrent risk of more than 50% as defined by Impact Genetics, or
  8. Monosomy of chromosome 3 with apical tumor height > 8mm (53).
  9. Archival tumor tissue is required for subjects that have had enucleation; subjects that have had enucleation but do not have available archival tissue are not eligible for participation. Archival tissue is required if available for subjects that have not had enucleation; if not available these patients are still eligible.
  10. Patients must have undergone an adequate treatment for the primary ocular melanoma deemed appropriate by the treating physician.
  11. All disease must be treated with no clinical, or radiologic evidence of residual ocular melanoma. All participants must have disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to registration. Imaging studies must include CT or MRI scans of the chest, abdomen, and pelvis. Brain MRI should be performed only as clinically indicated. NOTE: Participants with equivocal nodes ≥ 10 mm and < 15 mm in a short axis may be eligible after if confirmation with histology/cytology is available. If risk of biopsy is too high or biopsy is not feasible, two sequential CT or MRI scans should be available and showing no signs of progressive and measurable disease or PET/CT demonstrating no FDG uptake. The second scan should occur at least 4 weeks after the initial scan. Lymph nodes ≥ 10 mm in a short axis are defined as pathological. Nodes that have a short axis <10 mm are considered non-pathological.
  12. Patients must be registered within 180 days of the last treatment performed to render the patient free of disease.
  13. . Patient may have received prior radiation therapy to the primary site, including after the surgical resection. No systemic radiation for metastatic ocular melanoma is permitted.
  14. . Subject re-enrollment: This study permits the re-enrollment of a participant who has discontinued the study as a screen failure. If re-enrolled, the participant must be re-consented
  15. . Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration.
  16. Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3
  17. Platelets ≥ 100,000 cells/mm3
  18. Hemoglobin (Hgb) ≥ 9 g/dL (NOTE: The use of transfusion or to achieve Hgb ≥ 10 g/dl is acceptable)
  19. Serum creatinine ≤ 1.5 x institutional upper limit normal (IULN) OR eGFR > 30mL/min for participant with creatinine levels > 1.5 x ULN
  20. Bilirubin ≤ 1.5 x IULN (except subjects with Gilbert Syndrome who can have total bilirubin ≥ 3.0 mg/dL)
  21. Aspartate aminotransferase (AST) ≤ 3.0 x IULN
  22. Alanine aminotransferase (ALT) ≤ 3.0 x IULN
  23. Alkaline phosphatase ≤ 2.5 IULN
  24. . Neuropathy (sensory and motor) Grade ≤ 1 (CTCAE v4)
  25. . Females of childbearing potential must have a negative serum pregnancy test at screening and within 24 hours prior to initiation of study treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
  26. . Females of childbearing potential and non-vasectomized males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 5 months after last dose of study drug (females) and 7 months after last dose of study drug for (males). The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
  27. . As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

You CAN'T join if...

  1. Patients with evidence of distant metastases (stage IV ocular melanoma) are not eligible.
  2. Patients with local or orbital recurrence are not eligible.
  3. Patients with cutaneous, mucosal, acral or conjunctival melanoma are not eligible.
  4. Subjects with active, known, or suspected autoimmune disease. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment or conditions not expected to recur in the absences of an external trigger are permitted to enroll.
  5. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 years of study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  6. Participants with previous malignancies are excluded unless a complete remission was achieved at 12 months prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include but are not limited to, non-melanoma skin cancers; in situ bladder cancer, in situ gastric cancer, or in situ colon cancer; in situ cervical cancer/dysplasia; or breast carcinoma in situ).
  7. History of Grade ≥ 3 allergy to human monoclonal antibodies.
  8. Subjects who have had prior immunotherapy, including but not limited to interferon alfa-2b, PEG-IFN, anti-PD-1, anti-PD-L1, anti-CTLA4 intra-tumoral or vaccine therapies are not permitted to enroll.
  9. Psychological, familial, sociological, or geographical conditions that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the participant before registration in the trial.
  10. . Subjects who are receiving any other investigational agents.
  11. . Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring systemic therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  12. . Patients known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Note: Testing for HIV must be performed at sites where mandated locally.
  13. . Subjects who are unable or unwilling to discontinue use of prohibited medications.
  14. . Subject is a prisoner

Locations

  • University of California San Francisco accepting new patients
    San Francisco California 94158 United States
  • MD Anderson Cancer Center accepting new patients
    Houston Texas 77030 United States

Lead Scientist

  • Katy Tsai
    Assistant Professor, Medicine. Authored (or co-authored) 23 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Suthee Rapisuwon
ID
NCT03528408
Phase
Phase 2
Study Type
Interventional
Last Updated