Stereotactic Body Radiation Therapy with Ipilimumab and Nivolumab in Treating Patients with Metastatic Melanoma

Status: Approved

Description

This phase II trial studies how well stereotactic body radiation therapy works when given together with ipilimumab and nivolumab in treating patients with melanoma that has spread to other parts in the body. 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. Monoclonal antibodies, such as ipilimumab and nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving stereotactic body radiation therapy with ipilimumab and nivolumab may work better in treating patients with melanoma.

Eligibility Criteria

Inclusion Criteria

  • Histologic diagnosis of metastatic melanoma
  • Any number of prior systemic therapeutic regimens including chemotherapy, pathway inhibitors, biochemotherapy, investigational agents, and immunotherapies other than ipilimumab, nivolumab or other CTLA-4, PD-1 or PD-L1 inhibitors
  • Patients must have measurable disease in at least 2 non-radiated sites as defined by RECIST v1.1; all sites must be evaluated within 4 weeks prior to beginning therapy
  • Eligible for extra-central nervous system (CNS) SABR to 1-5 sites of disease
  • Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
  • Leukocytes >= 1,000/mcL
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 75,000/mcl
  • Total bilirubin =< 2.5 X institutional upper limit of normal or =< 3 in subjects with Gilbert’s syndrome
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 4 X institutional upper limit of normal
  • Creatinine =< 4 X institutional upper limit of normal
  • Hemoglobin >= 7 g/dL
  • Ability to understand and the willingness to sign a written informed consent
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of protocol treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; a female of child-bearing potential 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; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

Exclusion Criteria

  • No concomitant therapy with any of the following: IL2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; or other investigational therapies; all such therapies must have been discontinued >= 4 weeks prior to registration
  • No infection with human immunodeficiency virus (HIV) and no known history of hepatitis B or hepatitis C virus indicating acute or chronic infection or active tuberculosis (TB)
  • Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated (surgery or radiation) and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or localized adenocarcinoma of the cervix
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients must not be pregnant or nursing
  • Patients are excluded if they have a history of prior treatment with ipilimumab, CTLA-4 inhibitor or agonist, nivolumab, PD-1 or PD-L1 inhibitor
  • Subjects who have had major surgery within 2 weeks prior to first dose of drug
  • Subjects who have had radiation therapy within 2 weeks prior to first dose of drug
  • Uncontrolled adrenal insufficiency or active chronic liver disease
  • Any history of central nervous system (CNS) metastases that is not adequately treated (surgery or radiation) > 14 days prior to registration
  • Any active known or suspected autoimmune disease; 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
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug; inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease
  • Subjects with life expectancy < 6 months
  • Subjects receiving any other investigational or standard antineoplastic agents

Locations & Contacts

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Approved
Contact: Kevin V. Albuquerque
Phone: 214-645-7296
Email: kevin.albuquerque@utsouthwestern.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES;

I. To measure improvement in response rate—RR based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 when stereotactic ablative body radiation (SABR) is added to ipilimumab + nivolumab compared to historical data.

SECONDARY OBJECTIVES:

I. Measure and compare DCR—disease control rate defined as response plus stable disease based on RECISTv1.1 at 12, 24, 36 weeks versus historical data.

II. To measure tumor CD8+granzyme B+ T cells and FoxP3+ regulatory T cells (T regs) and tumor PD-L1 expression pre-treatment and post-treatment and correlate with response.

III. To determine the toxicity profile compared to historical controls.

OUTLINE:

Patients receive ipilimumab intravenously (IV) over 90 minutes and nivolumab IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients also undergo 1-3 fractions of stereotactic body radiation therapy on the same day or within 3 days of starting chemotherapy in weeks 1-2, and then receive nivolumab IV over 60 minutes on day 1 in weeks 13, 15, 19, 21, 23, 25, 27, 29, 31, 33, and 35 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, 6 months for 2 years, and then periodically thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
UT Southwestern / Simmons Cancer Center-Dallas

Principal Investigator
Kevin V. Albuquerque

Trial IDs

Primary ID SCCC-01616
Secondary IDs NCI-2017-01125, STU 082016-028
Clinicaltrials.gov ID NCT03126461