Testing Treatment With Ipilimumab and Nivolumab Compared to Treatment With Ipilimumab Alone in Advanced Melanoma
Condition: Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Melanoma of Unknown Primary; Mucosal Melanoma; Unresectable Cutaneous Melanoma; Unresectable Melanoma
MeSH terms: Melanoma; Skin Neoplasms
Intervention: Ipilimumab; Nivolumab
Intervention description: Given IV; Given IV
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well ipilimumab with or without nivolumab work in treating
      patients with melanoma that is stage IV or stage III and cannot be removed by surgery.
      Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the
      body's immune system attack the cancer, and may interfere with the ability of tumor cells to
      grow and spread.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have pathologically confirmed melanoma that is either stage IV or
             unresectable stage III; patients may have primaries of cutaneous, mucosal or unknown
             origin; patients with uveal (ocular) primary are not eligible

          -  Patients must have measurable disease per RECIST 1.1; all measurable lesions must be
             assessed by physical examination, computed tomography (CT) scans or magnetic resonance
             imaging (MRI) within 28 days prior to registration; if the only measurable disease is
             cutaneous or subcutaneous, lesions must be at least 10 mm in greatest dimension and
             able to be serially recorded using calipers and photographs; tests used to assess
             non-measurable disease must have been performed within 42 days prior to registration;
             all disease must be assessed and documented on the Baseline Tumor Assessment Form

          -  Patients with central nervous system (CNS) metastases must have all lesions adequately
             treated with stereotactic radiation therapy, craniotomy, Gamma Knife (registered
             trademark) therapy, or whole brain radiotherapy, with no subsequent evidence of CNS
             progression; patients must not have required steroids for at least 14 days prior to
             registration; patients with a history of central nervous system metastases must have
             MRI of the brain within 42 days prior to registration

          -  Patients must have had prior treatment with anti-PD1 or anti-PD-L1 agents and had
             documented disease progression per the treating physician either while on these agents
             or after stopping therapy with these agents without intervening therapy; patients who
             received adjuvant therapy for previously resected disease with PD-1 or PD-L1 agents
             may also be eligible if disease recurrence occurred while still receiving the PD-1 or
             PD-L1 therapy and no intervening therapy was received; patients must have discontinued
             anti-PD-1 or anti-PD-L1 therapy at least 21 days prior to registration

          -  Patients must be >= 18 years of age

          -  Patients must have Zubrod performance status of =< 2

          -  Patients must have complete history and physical examination within 28 days prior to
             registration

          -  Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days prior to registration)

          -  Hemoglobin >= 8 g/dL (within 28 days prior to registration)

          -  Platelets >= 100,000/mcL (within 28 days prior to registration)

          -  Total bilirubin =< 2.5 x institutional upper limit of normal (IULN) (except patients
             with Gilbert's syndrome) (within 28 days prior to registration)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 5 x IULN
             (within 28 days prior to registration)

          -  Serum creatinine =< 2.0 x IULN within 28 days prior to registration

          -  Patients with a known history of human immunodeficiency virus (HIV) must have CD4
             count >= institutional lower limit of normal within 28 days prior to registration

          -  Patients with a known history of congestive heart failure (CHF), cardiomyopathy,
             myocarditis, myocardial infarction (MI), exposure to cardiotoxic medications, or with
             a clinical history suggestive of the above must have an electrocardiography (EKG) and
             echocardiogram (ECHO) performed within 42 days prior to registration and as clinically
             indicated while on treatment

          -  Patients with new symptoms of congestive heart failure (CHF), cardiomyopathy,
             myocarditis, myocardial infarction (MI), or exposure to cardiotoxic medications must
             have a cardiology consultation, creatinine phosphokinase (CPK), and troponin testing
             at prestudy and as clinically indicated

          -  Males who are sexually active with women of reproductive potential must have agreed to
             use birth control throughout the study and for 7 months after completion of protocol
             treatment; in addition to routine contraceptive methods, "effective contraception"
             also includes heterosexual celibacy and surgery intended to prevent pregnancy
             (vasectomy); if at any point a previously celibate patient chooses to become
             heterosexually active during or within 7 months after completion of protocol
             treatment, he is responsible for beginning effective contraceptive measures

          -  Patients must submit archival tissue (if available) for translational medicine;
             patients must also be willing to undergo biopsies and submit tissue and blood for
             translational medicine

          -  Patients must be offered the opportunity to participate in specimen banking of
             leftover tissue for future research

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered in the system

        Exclusion Criteria:

          -  Patients must not have achieved a partial or complete response to the anti-PD-1 or
             anti-PD-L1 agents prior to progression per the treating physician

          -  Patients must not have had any systemic therapy, including anti-PD-1 or anti-PD-L1
             agents, within 21 days prior to registration

          -  Patients must not have had prior radiation therapy within 14 days prior to
             registration

          -  Patients must not have had:

               -  Prior treatment with ipilimumab or other CTLA-4 antagonists

               -  Systemic therapy between progression on the anti-PD-1 or anti-PD-L1 agents and
                  registration

               -  Note: Systemic therapy (including BRAF-targeting agents) prior to anti-PD-1 or
                  anti-PD-L1 therapy is allowed

          -  Patients must not be planning to require any additional form of systemic anti-tumor
             therapy while on protocol treatment

          -  Patients must not have known active hepatitis B virus (HBV) or hepatitis C virus (HCV)
             infection prior to registration

          -  Patients must not have an active infection requiring systemic therapy at time of
             registration

          -  Patients must not have organ allografts

          -  Patients must not have received systemic treatment with corticosteroids (> 10 mg daily
             prednisone or equivalent) or other immunosuppressive medications within 14 days prior
             to registration; inhaled or topical steroids, and adrenal replacement doses =< 10 mg
             daily prednisone or equivalent are permitted in the absence of active autoimmune
             disease

          -  Patients must not have a history of immune-mediated pneumonitis or colitis that
             required interruption of therapy or treatment of steroids

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             stage 0, I or II cancer from which the patient is currently in complete remission, or
             any other cancer from which the patient has been disease free for two years

          -  Patients must not be pregnant or nursing due to risk of fetal or nursing infant harm;
             females of reproductive potential must have negative serum pregnancy test within 2
             days prior to registration and agree to use an effective contraceptive method
             throughout the study and for 5 months after completion of protocol treatment; a woman
             is considered to be of "reproductive potential" if she has had menses at any time in
             the preceding 12 consecutive months; in addition to routine contraceptive methods,
             "effective contraception" also includes heterosexual celibacy and surgery intended to
             prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a
             hysterectomy, bilateral oophorectomy or bilateral tubal ligation; if at any point a
             previously celibate patient chooses to become heterosexually active during or within 5
             months after protocol treatment, she is responsible for beginning effective
             contraceptive measures