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

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ClinicalTrials.gov Identifier: NCT02989636
Recruitment Status : Recruiting
First Posted : December 12, 2016
Last Update Posted : December 12, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Bristol-Myers Squibb
Chordoma Foundation
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chordoma Other: Laboratory Biomarker Analysis Biological: Nivolumab Radiation: Stereotactic Radiosurgery Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Safety Study of Stereotactic Radiosurgery With Concurrent and Adjuvant PD-1 Antibody Nivolumab in Subjects With Recurrent or Advanced Chordoma
Actual Study Start Date : March 10, 2017
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Arm I (nivolumab)
Patients 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Experimental: Arm II (nivolumab, SRS)
Patients receive nivolumab as in Arm I. Patients undergo stereotactic radiosurgery (SRS) as per standard of care on day 8 of course 1.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Radiation: Stereotactic Radiosurgery
Undergo SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • Stereotactic Radiation Therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery




Primary Outcome Measures :
  1. 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 ]
    Proportion of serious adverse events will be estimated using the binomial distribution along with 95% confidence interval (exact method).



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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02989636


Contacts
Contact: Emma Gentry 4109557504 esheldo1@jhmi.edu
Contact: Jessica Wollett 4105027752 jwollet1@jhmi.edu

Locations
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Kelly K. Szajna, RN, BSN    410-502-4081    kszajna1@jhmi.edu   
Contact: Whitney Webb, RN, MSN    4109557008    wwebb10@jhmi.edu   
Principal Investigator: Michael K. Lim, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Michelle Mehallow    212-639-2739    mehallom@mskcc.org   
Contact: Emily Gelb    646-888-4592    gelbe@mskcc.org   
Principal Investigator: Yoshiya (Josh) Yamada, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Bristol-Myers Squibb
Chordoma Foundation
Investigators
Principal Investigator: Michael Lim Johns Hopkins University/Sidney Kimmel Cancer Center

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02989636     History of Changes
Other Study ID Numbers: J16138
IRB00117650 ( Other Identifier: JHM IRB )
NCI-2016-01638 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA006973 ( U.S. NIH Grant/Contract )
18-020 ( Other Identifier: MSKCC )
CA209-594 ( Other Identifier: BMS )
First Posted: December 12, 2016    Key Record Dates
Last Update Posted: December 12, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Chordoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs