Clinical Trials /

Study of Adjuvant Ipilimumab and Nivolumab in Subjects With High-risk Ocular Melanoma

NCT03528408

Description:

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

Related Conditions:
  • Ocular Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Adjuvant Ipilimumab and Nivolumab in Subjects With High-risk Ocular Melanoma
  • Official Title: Phase II Single-arm Multi-center Study of Adjuvant Ipilimumab in Combination With Nivolumab in Subjects With High-risk Ocular Melanoma

Clinical Trial IDs

  • ORG STUDY ID: HCRN-MEL17-309
  • NCT ID: NCT03528408

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab and Ipilimumab
IpilimumabYervoyNivolumab and Ipilimumab

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and IpilimumabExperimentalAll 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.
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          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:

               -  Gene Expression Profile using 15-gene panel (Castle Bioscience) and be classified
                  as Class 2, or

               -  3-year recurrent risk of more than 50% as defined by Impact Genetics, or

               -  Monosomy of chromosome 3 with apical tumor height > 8mm (53).

          6. 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.

          7. Patients must have undergone an adequate treatment for the primary ocular melanoma
             deemed appropriate by the treating physician.

          8. 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.

          9. Patients must be registered within 180 days of the last treatment performed to render
             the patient free of disease.

         10. 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.

         11. 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

         12. Demonstrate adequate organ function as defined in the table below. All screening labs
             to be obtained within 28 days prior to registration.

               -  Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3

               -  Platelets ≥ 100,000 cells/mm3

               -  Hemoglobin (Hgb) ≥ 9 g/dL (NOTE: The use of transfusion or to achieve Hgb ≥ 10
                  g/dl is acceptable)

               -  Serum creatinine ≤ 1.5 x institutional upper limit normal (IULN) OR eGFR >
                  30mL/min for participant with creatinine levels > 1.5 x ULN

               -  Bilirubin ≤ 1.5 x IULN (except subjects with Gilbert Syndrome who can have total
                  bilirubin ≥ 3.0 mg/dL)

               -  Aspartate aminotransferase (AST) ≤ 3.0 x IULN

               -  Alanine aminotransferase (ALT) ≤ 3.0 x IULN

               -  Alkaline phosphatase ≤ 2.5 IULN

         13. Neuropathy (sensory and motor) Grade ≤ 1 (CTCAE v4)

         14. 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.

         15. 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.

         16. 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

        Exclusion Criteria:

          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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:3 year Relapse Free Survival (RFS)
Time Frame:36 months
Safety Issue:
Description:RFS is defined as time from registration to recurrence of disease or death from any cause.

Secondary Outcome Measures

Measure:Median RFS
Time Frame:12 months
Safety Issue:
Description:RFS is defined as time from registration to recurrence of disease or death from any cause
Measure:Overall Survival (OS)
Time Frame:12 months
Safety Issue:
Description:OS is defined as the time from registration until death from any cause
Measure:3 year OS
Time Frame:36 months
Safety Issue:
Description:OS is defined as the time from registration until death from any cause
Measure:Assess Adverse Events
Time Frame:36 months
Safety Issue:
Description:Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Suthee Rapisuwon

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