Clinical Trials /

Nivolumab With or Without Stereotactic Radiosurgery in Treating Patients With Recurrent, Advanced, or Metastatic Chordoma

NCT02989636

Description:

This phase I trial studies the side effects of nivolumab with or without stereotactic radiosurgery (SRS) in treating patients with chordoma that has come back or spread from where it started to other places in the body. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. It is not yet known whether giving nivolumab with or without stereotactic radiosurgery may work better in treating patients with chordoma.

Related Conditions:
  • Chordoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab With or Without Stereotactic Radiosurgery in Treating Patients With Recurrent, Advanced, or Metastatic Chordoma
  • Official Title: Phase I Safety Study of Stereotactic Radiosurgery With Concurrent and Adjuvant PD-1 Antibody Nivolumab in Subjects With Recurrent or Advanced Chordoma

Clinical Trial IDs

  • ORG STUDY ID: J16138
  • SECONDARY ID: IRB00117650
  • SECONDARY ID: NCI-2016-01638
  • SECONDARY ID: P30CA006973
  • SECONDARY ID: 18-020
  • SECONDARY ID: CA209-594
  • NCT ID: NCT02989636

Conditions

  • Chordoma

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoArm I (nivolumab)

Purpose

This phase I trial studies the side effects of nivolumab with or without stereotactic radiosurgery (SRS) in treating patients with chordoma that has come back or spread from where it started to other places in the body. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. It is not yet known whether giving nivolumab with or without stereotactic radiosurgery may work better in treating patients with chordoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the safety profile of nivolumab alone and nivolumab in combination with
      stereotactic radiosurgery to treat patients with recurrent or advanced chordoma.

      SECONDARY OBJECTIVES:

      I. To evaluate toxicity and tolerability of nivolumab alone and nivolumab in combination with
      stereotactic radiosurgery.

      II. To estimate growth modulation index on target lesion. III. To estimate a clinical
      response (partial response [PR] + complete response [CR] within 6 month + stable disease [SD]
      beyond 6 months).

      IV. To assess progression-free survival and progression-free survival (PFS) rate at 6 months.

      V. To assess overall survival rate at 1 year, 3 years and 5 years.

      TERTIARY OBJECTIVES:

      I. To explore peripheral blood immune response during and after treatment.

      OUTLINE: Patients are assigned to 1 of 2 arms.

      ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat
      every 14 days for 2 years in the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive nivolumab as in Arm I. Patients undergo stereotactic radiosurgery
      (SRS) as per standard of care on day 8 of course 1.

      After completion of study treatment, patients are followed up at 100 days and every 10 weeks
      thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (nivolumab)ExperimentalPatients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 14 days for 8 doses, then every 28 days for a total of 2 years in the absence of disease progression or unacceptable toxicity.
  • Nivolumab
Arm II (nivolumab, SRS)ExperimentalPatients receive nivolumab as in Arm I. Patients undergo stereotactic radiosurgery (SRS) as per standard of care on day 8 of course 1.
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of chordoma; the pathologic
             confirmation may be from another metastatic site

          -  Patients may have metastases, with newly identified peripheral metastases

          -  Cross-sectional imaging evidence of progression of recurrent or metastatic disease

          -  Previous treatment information (name of agent, treatment starting date, and date of
             progression) must be available for review

          -  Measurable disease in at least one site

          -  Karnofsky performance scale >= 70%

          -  White blood cells (WBC) >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< 2 x institutional upper limit of normal

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =<
             2.5 x institutional upper limit of normal

          -  Creatinine within normal institutional limits OR according to Johns Hopkins magnetic
             resonance imaging (MRI) policy

          -  Women of child bearing potential (WOCBP) should use an adequate method to avoid
             pregnancy for 5 months plus the time required for nivolumab to undergo approximately
             five half-lives) after the last dose of investigational drug; in order for a woman to
             be determined not of child-bearing potential, she must have >= 12 months of
             non-therapy induced amenorrhea or be surgically sterile

          -  Men receiving nivolumab and who are sexually active with WOCBP will be instructed to
             adhere to contraception for a period of 7 months after the last dose of
             investigational product

          -  Ability to understand and the willingness to sign written informed consent document(s)

        Exclusion Criteria:

          -  Prior chemotherapy within 21 days or 5 half-lives (whichever is shorter) days of
             starting treatment

          -  Prior therapy with investigational drugs within 28 days or at least 5 half-lives
             (whichever is shorter) before study administration

          -  Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL-2 antibody

          -  Neurologic dysfunction that would confound the evaluation of neurologic and other
             adverse events

          -  Known allergy to compounds of similar chemical or biologic composition to nivolumab

          -  Pregnant or breastfeeding women

          -  Known history of human immunodeficiency virus

          -  Active infection requiring therapy, including positive tests for hepatitis B surface
             antigen or hepatitis C ribonucleic acid (RNA)

          -  Active autoimmune disease, history of autoimmune disease or history of syndrome that
             required systemic steroids or immunosuppressive medications, e.g. organ, tissue, or
             allogenic hematopoietic stem cell transplant (HSCT) recipients. Exceptions include
             those with resolved childhood asthma/atopy. Subjects with asthma who require
             intermittent use of bronchodilators (such as albuterol) will not be excluded from this
             study. Subjects are also permitted to enroll if they have 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

          -  Patients should be excluded if they have a condition requiring systemic treatment with
             either corticosteroids (> 10 mg daily prednisone equivalents) or other
             immunosuppressive medications within 14 days of study drug administration; inhaled or
             topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents
             are permitted in the absence of active autoimmune disease

          -  Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up
             to 4 weeks (28 days) before receiving nivolumab

          -  Prisoners or subjects who are compulsorily detained for treatment of either a
             psychiatric or physical (e.g. infectious disease) illness

          -  Prior radiation doses equivalent to, or greater than, 8000 cGy in 200 cGy fractions

          -  Any radiation to the target lesions within 6 months of enrollment

          -  Unable to meet radiation treatment plan parameters

          -  Unavailable for follow up visits after treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:15 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame:Up to 12 weeks after initial dose of nivolumab
Safety Issue:
Description:Proportion of serious adverse events will be estimated using the binomial distribution along with 95% confidence interval (exact method).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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