Clinical Trials /

Nivolumab and Ipilimumab and Stereotactic Body Radiation Therapy in Treating Patients With Salivary Gland Cancers

NCT03749460

Description:

This phase I/II trial studies the side effects and how well nivolumab and ipilimumab works when given together with stereotactic body radiation therapy (SBRT) in treating patients with salivary gland cancers. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving nivolumab and ipilimumab and SBRT may work better in treating patients with advanced salivary gland cancers.

Related Conditions:
  • Salivary Gland Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Ipilimumab and Stereotactic Body Radiation Therapy in Treating Patients With Salivary Gland Cancers
  • Official Title: Dual Immune Checkpoint Blockade and Hypofractionated Radiation in Patients With Salivary Gland Cancers

Clinical Trial IDs

  • ORG STUDY ID: RG1718030
  • SECONDARY ID: NCI-2018-02473
  • SECONDARY ID: 8758
  • NCT ID: NCT03749460

Conditions

  • Larynx
  • Lip
  • Oral Cavity Cancer
  • Pharynx Cancer

Interventions

DrugSynonymsArms
Nivolumab946414-94-4, BMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab, ipilimumab, SBRT)
Ipilimumab477202-00-9, 720801, 732442, Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyTreatment (nivolumab, ipilimumab, SBRT)

Purpose

This phase I/II trial studies the side effects and how well nivolumab and ipilimumab works when given together with stereotactic body radiation therapy (SBRT) in treating patients with salivary gland cancers. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving nivolumab and ipilimumab and SBRT may work better in treating patients with advanced salivary gland cancers.

Detailed Description

      Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats
      every 2 weeks for up to 12 courses and then every 4 weeks for additional 8 courses in the
      absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab IV
      over 60 minutes on day 1. Treatment repeats every 6 weeks for up to 4 courses in the absence
      of disease progression or unacceptable toxicity. Beginning week 3, patients undergo 3
      fractions of stereotactic body radiation therapy every other day in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment patients are followed up at 30 days and then every 8 or
      12 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab, ipilimumab, SBRT)ExperimentalPatients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for up to 12 courses and then every 4 weeks for an additional 8 courses in the absence of disease progression or unacceptable toxicity. Patients also receive ipilimumab IV over 60 minutes on day 1. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Beginning week 3, patients undergo 3 fractions of stereotactic body radiation therapy every other day in the absence of disease progression or unacceptable toxicity.
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically proven salivary gland carcinoma (World Health Organization [WHO], 2005)
             arising from a previous head and neck primary site, and located within the head and
             neck region, lung or bone, and who are not candidates for curative intent therapy

          -  Demonstrated disease progression during, or after discontinuation, of the most recent
             line of systemic therapy

          -  Have received any number lines of prior systemic therapy (including systemic therapy
             in the curative intent setting)

          -  Have a target lesion/s deemed suitable by the treating physicians for stereotactic
             body radiation therapy (SBRT) with the intent of palliation or prevention of symptoms.
             This lesion must be:

               -  1-3 non-overlapping sites in the head and neck region OR

               -  Metastatic lesions outside the head and neck (H&N) region in the lung or bone (a
                  minimum of 1 and a maximum 5 lesions will be irradiated), provided there is no
                  significant overlap between the lesions

                    -  Patients should have RECIST 1.1 criteria measurable disease in addition to
                       the lesion/s treated with SBRT. If the site/s of SBRT were previously
                       radiated to high dose radiation therapy (RT) (> 50Gy), there should be > 6
                       month time interval between the last dose of radiation and the start of SBRT

          -  Have the ability to tolerate required SBRT-related procedures (e.g.: lie flat and hold
             position for treatment) as determined by the treating physician

          -  Be willing and able to provide written informed consent for the trial and comply with
             the study visit requirements

          -  Have measurable disease based on RECIST 1.1. (in addition to the lesion/s that will be
             treated with stereotactic radiation therapy)

          -  Have provided tissue from an archival tissue sample or newly obtained core or
             excisional biopsy of a tumor lesion. Tissue requirement will be waived if deemed
             contraindicated or not clinically available/accessible for resection per the treating
             physician (principal investigator [PI] approval required)

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Hemoglobin >= 9.0 g/dL (performed within 10 days of treatment initiation)

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L (>= 1500 per mm^3) (performed within
             10 days of treatment initiation)

          -  Platelet count >= 100 x 10^9 /L (>= 100,000 per mm^3) (performed within 10 days of
             treatment initiation)

          -  Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will not
             apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent
             hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
             hepatic pathology), who will be allowed only in consultation with their physician
             (performed within 10 days of treatment initiation)

          -  Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal unless liver metastases are present, in
             which case it must be =< 5 x ULN (performed within 10 days of treatment initiation)

          -  Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula (Cockcroft
             and Gault 1976) or by 24-hour urine collection for determination of creatinine
             clearance (performed within 10 days of treatment initiation)

          -  Evidence of post-menopausal status OR negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered post-menopausal if they have
             been amenorrheic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

               -  Women < 50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy, or hysterectomy)

               -  Women >= 50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses > 1 year ago, had
                  chemotherapy-induced menopause with last menses > 1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy)

          -  Female subjects of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Female subjects of childbearing potential should be willing to use 1 method of highly
             effective birth control or be surgically sterile, or abstain from heterosexual
             activity for the course of the study through 180 days after the last dose of study
             medication. Subjects of childbearing potential are those who have not been surgically
             sterilized or have not been free from menses for > 1 year

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 180 days after the last dose of study therapy

          -  Patient is >= 5 years free of another primary malignancy, except:

               -  If the other malignancy is basal cell carcinoma or cervical carcinoma in situ or

               -  If the other primary malignancy is not considered clinically significant and is
                  requiring no active intervention

        Exclusion Criteria:

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of treatment

          -  Has a target lesion/s for SBRT that demonstrate any of the following:

               -  Located within 2 cm of the proximal bronchial tree

               -  > 5 cm (> 50 cc) in greatest dimension

          -  Has a target lesion/s in a region that previously received high dose radiation therapy
             (RT) (> 50 Gy) demonstrating any of the following:

               -  Carotid artery encasement (> 180 degrees) (due to risk of carotid blow out)

               -  Unprotected carotid artery (i.e. skin is directly over the carotid without
                  intervening soft tissue, especially after prior neck dissection without a
                  vascularized free flap) (due to risk of carotid blow out)

               -  Skin infiltration by tumor (due to risk of fistula)

               -  Located in the larynx/hypopharynx primaries (due airway threat)

               -  Treated with high dose radiation therapy (> 50 Gy) within 6 months or less of
                  trial enrollment

          -  Prior receipt of an anti-PD-1, anti-PDL1 or anti-CTLA4 immune checkpoint inhibitor

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of nivolumab or ipilimumab. The following are exceptions to this criterion:

               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
                  articular injection)

               -  Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
                  prednisone or its equivalent

               -  Steroids as premedication for hypersensitivity reactions (e.g., computed
                  tomography [CT] scan premedication)

          -  Has received a prior monoclonal antibody within 4 weeks prior to study Day 1 or who
             has not recovered (i.e., =< Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier

          -  Has received prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., =< Grade 1 or at
             baseline) from adverse events due to a previously administered agent.

               -  Note: Subjects with =< Grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting therapy

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy

          -  Has known brain metastases or spinal cord compression unless the patient is stable
             (asymptomatic; no evidence of new or emerging brain metastases; and stable and off
             steroids for at least 14 days prior to start of study treatment). Following
             radiotherapy and/or surgery of the brain metastases patients must wait 4 weeks
             following the intervention and before initiating study treatment with imaging to
             confirm stability

          -  Has an active autoimmune disease requiring systemic treatment within the past 2 years
             or a documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or
             resolved childhood asthma/atopy would be an exception to this rule. Subjects that
             require intermittent use of bronchodilators or local steroid injections would not be
             excluded from the study. Subjects with hypothyroidism stable on hormone replacement
             will not be excluded from the study

          -  Has a history of or evidence of active interstitial lung disease or non-infectious
             pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 180 days after the last dose of trial treatment

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has evidence of acute or chronic hepatitis B, or hepatitis C

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment

          -  Has a history of primary immunodeficiency or an allogeneic organ transplant

          -  Known history of previous clinical diagnosis of tuberculosis

          -  Uncontrolled intercurrent illness including, but not limited to symptomatic congestive
             heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac
             arrhythmia, active peptic ulcer disease or gastritis, seizures
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs)
Time Frame:Up to 100 days post-treatment
Safety Issue:
Description:Adverse events will be recorded and graded based on Common Terminology Criteria for Adverse Events (CTCAE) version 5, and their relationship to the experimental agents reported.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 4 years
Safety Issue:
Description:Clinical responses to the combination of nivolumab, ipilimumab and hypofractionated radiation will be based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Measure:Progression-free survival (PFS)
Time Frame:From the date of study enrollment, until disease progression or death, assessed up to 4 years
Safety Issue:
Description:PFS estimate will be calculated using the Kaplan-Meier method.
Measure:Overall survival (OS)
Time Frame:From the date of study enrollment, until disease progression or death, assessed up to 4 years
Safety Issue:
Description:OS estimate will be calculated using the Kaplan-Meier method.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Trial Keywords

  • Metastatic Malignant Neoplasm in the Bone
  • Metastatic Malignant Neoplasm in the Lung
  • Salivary Gland Carcinoma
  • Stage IV Major Salivary Gland Cancer AJCC v8
  • Stage IVA Major Salivary Gland Cancer AJCC v8
  • Stage IVB Major Salivary Gland Cancer AJCC v8
  • Stage IVC Major Salivary Gland Cancer AJCC v8

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