Phase I Safety Study of Stereotactic Radiosurgery With Concurrent and Adjuvant PD-1 Antibody Nivolumab in Subjects With Recurrent or Advanced Chordoma
概览
- 阶段
- 1 期
- 干预措施
- Nivolumab
- 疾病 / 适应症
- Chordoma
- 发起方
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Incidence of dose limiting toxicities evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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 one or more site. (Per RECIST criteria: Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm with CT scan, MRI, or calipers by clinical exam. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters)).
- •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
排除标准
- •Prior chemotherapy within 21 days or 5 half-lives (whichever is shorter) days of starting treatment
- •Prior therapy with investigational drugs within 21 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
研究组 & 干预措施
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.
干预措施: Nivolumab
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Laboratory Biomarker Analysis
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.
干预措施: Nivolumab
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.
干预措施: Stereotactic Radiosurgery
结局指标
主要结局
Incidence of dose limiting toxicities evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
时间窗: 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).