Clinical Trials /

Nivolumab and Ipilimumab in Treating Patients With Metastatic/Recurrent ACC of All Sites and Non-ACC Salivary Gland Cancer

NCT03146650

Description:

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.

Related Conditions:
  • Salivary Gland Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Ipilimumab in Treating Patients With Metastatic/Recurrent ACC of All Sites and Non-ACC Salivary Gland Cancer
  • Official Title: Phase II Study of Nivolumab and Ipilimumab for Treatment of Metastatic/Recurrent Adenoid Cystic Carcinoma of All Anatomic Sites of Origin and Non-adenoid Cystic Carcinoma Malignant Tumors of the Salivary Gland

Clinical Trial IDs

  • ORG STUDY ID: NU 16N03
  • SECONDARY ID: STU00204579
  • SECONDARY ID: NU 16N03
  • SECONDARY ID: P30CA060553
  • SECONDARY ID: NCI-2017-00406
  • NCT ID: NCT03146650

Conditions

  • 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

Interventions

DrugSynonymsArms
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyTreatment (nivolumab, ipilimumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab, ipilimumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess median progression-free survival rate (PFSR) as well as PFSR at 6 and 12 months
      in patients with recurrent or metastatic adenoid cystic carcinoma (ACC) treated with a
      combination of nivolumab and ipilimumab.

      SECONDARY OBJECTIVES:

      I. To assess the efficacy of nivolumab and ipilimumab according to response rate (RR),
      disease control rate (DCR; complete response [CR], partial response [PR], and stable disease
      [SD] at 6 and 12 months), overall survival (OS) and progression free survival (PFS) using
      Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with recurrent or
      metastatic ACC.

      II. To assess the efficacy of nivolumab and ipilimumab according to overall response rate
      (ORR), DCR, progression free survival (PFS), and OS in patients with recurrent or metastatic
      ACC using immune-related response criteria (irRC) criteria.

      III. To assess the safety and tolerability profile of nivolumab and ipilimumab therapy in
      patients with recurrent or metastatic ACC using Common Terminology Criteria for Adverse
      Events (CTCAE) version 4.03.

      TERTIARY OBJECTIVES:

      I. Assess safety, tolerability and activity of Nivolumab and Ipilimumab in non-ACC malignant
      salivary gland tumors (MSGT's) using clinical benefit rate (CBR), ORR, PFS, OS.

      II. To assess the predictive value of genomic aberrations observed upon comprehensive genomic
      profiling of the tumor deoxyribonucleic acid (DNA) derived from archival tumor tissue, if
      available, or blood from patients with recurrent or metastatic ACC and non-ACC MSGTs.

      III. Circulating cell free DNA genomic profiling will also be performed at baseline and
      during treatment with each imaging to explore the genomic landscape of clonal evolution that
      may elucidate mechanisms behind response or resistance with immunotherapy in adenoid cystic
      carcinoma and non-ACC MSGTs.

      IV. Correlation between expression of PD-L1 and response to treatment will be explored in all
      patients enrolled in the study.

      V. Correlations between other markers of inflammatory/immune signature will be performed that
      may include but not be limited to PD-1, OX40, CD73, CD39, T cell immunoglobulin and mucin
      domain containing protein 3 (TIM3), GITRL, CTLA-4, CD3, CD4, CD8, protein tyrosine
      phosphatase receptor type C (CD45RO), forkhead box P3 (FOXP3), and granzyme by
      immunohistochemistry analysis and/or flow cytometry.

      OUTLINE:

      Patients receive nivolumab intravenously (IV) over 30 minutes on days 1, 15, 29, 43, 57, and
      71 of course 1 and on days 1 and 15 of course 2, over 60 minutes on days 29 and 57 of course
      2 and on days 1, 29, and 57 of subsequent courses. Patients also receive ipilimumab over 90
      minutes on days 1 and 43. Courses repeat every 84 days in the absence of disease progression,
      unexpected toxicity, or withdrawal of consent.

      After completion of study treatment, patients are followed up for 30 days, every 4 weeks for
      12 weeks, and then every 12 weeks for up to 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab, ipilimumab)ExperimentalPatients receive nivolumab IV over 30 minutes on days 1, 15, 29, 43, 57, and 71 of course 1 and on days 1 and 15 of course 2, over 60 minutes on days 29 and 57 of course 2 and on days 1, 29, and 57 of subsequent courses. Patients also receive ipilimumab over 90 minutes on days 1 and 43. Courses repeat every 84 days in the absence of disease progression or unexpected toxicity.
  • Ipilimumab
  • Nivolumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Median PFS (median Progression-Free Survival)
Time Frame:Up to 2 years
Safety Issue:
Description:Median PFS will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.

Secondary Outcome Measures

Measure:Response Rate (RR)
Time Frame:Up to 2 years
Safety Issue:
Description:RR will be evaluated by RECIST 1.1 in patients with recurrent or metastatic ACC.
Measure:Disease Control Rate (DCR)
Time Frame:At 6 months
Safety Issue:
Description:DCR will be defined as the sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) and will be assessed by RECIST 1.1 in patients with recurrent or metastatic ACC.
Measure:Disease Control Rate (DCR)
Time Frame:At 12 months
Safety Issue:
Description:DCR will be defined as the sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) and will be assessed by RECIST 1.1 in patients with recurrent or metastatic ACC.
Measure:Overall Survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:Overall survival (OS) is defined as time in months from the date of first study treatment to the date of death and will be evaluated using RECIST 1.1 criteria.
Measure:PFS (RECIST 1.1 criteria)
Time Frame:Up to 2 years
Safety Issue:
Description:PFS defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR will be assessed by immune-related response (irRECIST) criteria in patients with recurrent or metastatic ACC.
Measure:DCR (irRECIST)
Time Frame:At 6 months
Safety Issue:
Description:DCR will be defined as the sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) and will be assessed by irRECIST in patients with recurrent or metastatic ACC.
Measure:DCR (irRECIST)
Time Frame:At 12 months
Safety Issue:
Description:DCR will be defined as the sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) and will be assessed by irRECIST in patients with recurrent or metastatic ACC.
Measure:PFS (irRECIST criteria)
Time Frame:Up to 2 years
Safety Issue:
Description:PFS will be evaluated using irRECIST criteria.
Measure:OS (irRECIST)
Time Frame:Up to 2 years
Safety Issue:
Description:OS is defined as time in months from the date of first study treatment to the date of death and will be evaluated using irRECIST criteria.
Measure:Incidence of Adverse Events
Time Frame:30 days after study treatment
Safety Issue:
Description:Assess the safety and tolerability of the combination of nivolumab and ipilimumab by evaluating the number, frequency, and severity of adverse events using CTCAE version 4.03.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Northwestern University

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