Nivolumab and Ipilimumab in Treating Patients With Metastatic/Recurrent ACC of All Sites and Non-ACC Salivary Gland Cancer
Condition: Major Salivary Gland Carcinoma; Minor Salivary Gland Carcinoma; Recurrent Salivary Gland Carcinoma; Stage IV Major Salivary Gland Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVC Major Salivary Gland Carcinoma
MeSH terms: Carcinoma; Salivary Gland Neoplasms; Recurrence
Intervention: Ipilimumab; Laboratory Biomarker Analysis; Nivolumab
Intervention description: Given IV; Correlative studies; Given IV
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the efficacy (the effect on the tumor) and the safety (the effect
      on the body) of the study drugs when given as a combination in participants with this type of
      cancer. Another purpose of the study is to see which tumor markers (proteins in the blood
      that the body produces in response to the cancer) lead to better results in participants
      treated with the study drugs. Nivolumab and ipilimumab are antibodies, which are human
      proteins that recognize and attach to a part of the tumor and/or body's immune cells. They
      work in slightly different ways to activate the immune system and help the body's immune
      system to work against tumor cells. Nivolumab and ipilimumab are investigational because they
      are not approved by the FDA to be used for the type of cancer being studied.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed metastatic/recurrent
             adenoid cystic carcinoma (ACC) or non-adenoid cystic carcinomas (non-ACC) of major or
             minor salivary glands

          -  Patients must have evidence of disease progression and cannot be a candidate for
             surgical treatment

               -  NOTE: Disease progression is defined as one of the following occurring within the
                  6 months prior to study entry:

                    -  At least a 20% increase in radiologically or clinically measurable lesions

                    -  Appearance of any new lesions or

                    -  Symptomatic and/or deterioration in clinical status

          -  Patients must have received at least one prior line of systemic therapy

               -  NOTE: There is no limit to the number of prior therapies for stage IV disease

               -  NOTE: Patients should not be a candidate for surgical treatment

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension in accordance with RECIST criteria v1.1

          -  Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) status of 0-2

               -  NOTE: ECOG performance status 3 will be allowed only if thought to be directly
                  secondary to adenoid cystic carcinoma disease by treating physician

          -  Patients must have adequate organ and bone marrow function within 14 days prior to
             registration, as defined by: leukocytes >= 2,000/mcL

          -  Patients must have adequate organ and bone marrow function within 14 days prior to
             registration, as defined by: absolute neutrophil count >= 1,500/mcL, regardless of
             transfusion or growth factor support

          -  Patients must have adequate organ and bone marrow function within 14 days prior to
             registration, as defined by: platelets >= 100,000/mcl, regardless of transfusion or
             growth factor support

          -  Patients must have adequate organ and bone marrow function within 14 days prior to
             registration, as defined by: total bilirubin total bilirubin =< 1.5 x institutional
             upper limit of normal (ULN) (except patients with Gilbert syndrome or liver
             metastasis, who can have total bilirubin < 3.0 x ULN)

          -  Patients must have adequate organ and bone marrow function within 14 days prior to
             registration, as defined by: aspartate aminotransferase (AST) (serum
             glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum
             glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
             (ULN) (or =< 5 times ULN in case of liver metastasis)

          -  Patients must have adequate organ and bone marrow function within 14 days prior to
             registration, as defined by: serum creatinine of < 3.0 X ULN (upper limit of normal)
             or creatinine clearance > 30 mL/minute (using Cockcroft/Gault formula)

          -  Patients with history of central nervous system (CNS) metastases are eligible if CNS
             disease has been stable for at least 6 weeks prior to study registration in the
             opinion of the investigator and does not require corticosteroids (of any dose) for
             symptomatic management

               -  NOTE: Only patients with a known history or indication of CNS disease are
                  required to have CNS imaging prior to study entry

          -  Females of childbearing potential (FOCBP) must have a negative serum or urine
             pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72
             hours of registration

               -  NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a
                  tubal ligation, or remaining celibate by choice) who meets the following
                  criteria:

                    -  Has not undergone a hysterectomy or bilateral oophorectomy

                    -  Has had menses at any time in the preceding 12 consecutive months (and
                       therefore has not been naturally postmenopausal for > 12 months)

          -  FOCBP and men who are sexually active with FOCBP must agree to follow instructions for
             method(s) of contraception for the duration of treatment and the designated
             post-treatment period

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent prior to registration on study

        Exclusion Criteria:

          -  Patients must not have had chemotherapy or radiotherapy =< 28 days prior to study
             registration

          -  Patients who have not recovered to =< grade 1 or tolerable grade 2 from adverse events
             due to agents administered >= 28 days earlier are not eligible

          -  Patient must not be a candidate for surgical treatment or radiation

          -  Patients may not be receiving any other investigational agents =< 28 days prior to
             registration

          -  Patients who have had prior exposure to immune checkpoint inhibitors are not eligible;
             please contact principal investigator, 312-926-4248 for specific questions on
             potential interactions

               -  NOTE: Immune checkpoint inhibitors working through OX40 are an exception (for
                  example, MEDI6383, MEDI6469, MEDI0562, oxelumab, and PF-04518600) and are
                  permitted >= 28 days prior to study registration

          -  Patients with active autoimmune disease or history of autoimmune disease that might
             recur, which may affect vital organ function or require immune suppressive treatment
             including chronic prolonged systemic corticosteroids (defined as corticosteroid use of
             duration one month or greater), should be excluded; these include but are not limited
             to patients with a history of:

               -  Immune related neurologic disease

               -  Multiple sclerosis

               -  Autoimmune (demyelinating) neuropathy

               -  Guillain-Barre syndrome

               -  Myasthenia gravis

               -  Systemic autoimmune disease such as SLE

               -  Connective tissue diseases

               -  Scleroderma

               -  Inflammatory bowel disease (IBD)

               -  Crohn's

               -  Ulcerative colitis

               -  Patients with a history of toxic epidermal necrolysis (TEN)

               -  Stevens-Johnson syndrome

               -  Anti-phospholipid syndrome

               -  NOTE: Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism
                  due to autoimmune condition only requiring hormone replacement, psoriasis not
                  requiring systemic treatment, or conditions not expected to recur in the absence
                  of an external trigger are permitted to enroll

          -  Patients who have an uncontrolled intercurrent illness including, but not limited to
             any of the following, are not eligible:

               -  Ongoing or active infection (including minor localized infections) requiring oral
                  or IV treatment

               -  Symptomatic class 3 or 4 congestive heart failure, defined as a clinical syndrome
                  resulting from any structural or functional cardiac disorder that impairs the
                  ability of the ventricle to fill with or eject blood

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

               -  Any other illness or condition that the treating investigator feels would
                  interfere with study compliance or would compromise the patient's safety or study
                  endpoints

          -  Patients should not have any condition requiring systemic treatment with
             corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive
             medications within 14 days prior to first dose of study drug

               -  NOTE: Inhaled or topical steroids and adrenal replacement steroids at any dose
                  are permitted in the absence of active autoimmune disease; a brief (less than 3
                  weeks) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or
                  for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity
                  reaction caused by a contact allergen) is permitted

          -  Female patients who are pregnant or nursing are not eligible

          -  No other prior malignancy is allowed except for the following:

               -  Adequately treated basal cell or squamous cell skin cancer,

               -  In situ cervical cancer,

               -  Or any other cancer from which the patient has been disease free for at least
                  three years

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS) is not permitted

          -  Any known positive test for hepatitis B or hepatitis C virus indicating acute or
             chronic infection is not permitted

          -  Patients who received a live, attenuated vaccine =< 30 days before study registration
             or are anticipated to require such a live attenuated vaccine are not eligible

               -  NOTE: Influenza vaccination should be given during influenza season only
                  (approximately October to March); patients must not receive live, attenuated
                  influenza vaccine (e.g., FluMist) =< 30 days prior to study registration or at
                  any time during the study