Nivolumab in Combination With Chemoradiation for Patients With Stage II-IVB Nasopharyngeal Carcinoma, A Phase II Study With Correlative Biomarkers
概览
- 阶段
- 2 期
- 干预措施
- Nivolumab
- 疾病 / 适应症
- Nasopharyngeal Carcinoma
- 发起方
- Sue Yom
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Rate of Completion of All Adjuvant Immunotherapy
- 状态
- 已完成
- 最后更新
- 3个月前
概览
简要总结
This phase II trial studies how well nivolumab and chemoradiotherapy works in treating patients with stage II-IVB nasopharyngeal cancer. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells. Chemoradiotherapy is the combination of chemotherapy and radiation therapy and may prevent the cancer from spreading when combined with nivolumab. Giving nivolumab and chemoradiotherapy may work better in treating patients with stage II-IVB nasopharyngeal cancer.
详细描述
PRIMARY OBJECTIVES: I. To establish the feasibility of treatment completion of a combined chemoradiation-nivolumab regimen followed by adjuvant nivolumab. SECONDARY OBJECTIVES: I. To determine the overall response rate at 1 year from end of treatment, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. II. To determine the locoregional control rate at 1 year post-treatment. III. To determine the distant metastasis rate at 1 year post-treatment. IV. To determine the rate of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) clearance at end of chemoradiation and at 1 year from end of treatment. V. To determine the acute and late toxicity rates according to Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5, including immune-related adverse events (AEs). VI. To assess patients' quality of life from baseline through 1 year from end of treatment. EXPLORATORY OBJECTIVES: I. To determine the overall survival rate at 5-year post-treatment. II. To determine whether programmed death-ligand 1 (PD-L1) -positive immunohistochemistry and novel quantitative assays correlate to clinical outcome. III. To determine if the density of infiltrating Cluster of differentiation 3 (CD3)+ T cells/μm2 correlates to clinical outcome. IV. To monitor immune changes by flow cytometry in the circulating T cell response to EBV antigens. V. To compare the change in the circulating T-cell repertoire by TCR sequencing and single-cell T-cell profiling. VI. To quantify treatment-induced changes over time in the circulating T cell immune response to EBV using T-cell receptor (TCR) sequencing and enzyme-linked immunospot (ELISPOT) assays. OUTLINE: Patients receive nivolumab intravenously (IV) over 60 minutes on day 1 of courses 1-5 and 7-12. Treatment repeats every 14 days for 11 courses in the absence of disease progression or unacceptable toxicity. Beginning at course 2, patients undergo radiation therapy once daily (QD) 5 days per week and receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 7 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1, 3, 6, 9, and 12 months for up to 1 year and then survival follow-up information may be collected via telephone calls, clinic follow-up visits, or medical records review for up to an additional 4 years. Survival and disease status will be collected until participant death, withdrawal, or if the participant is lost to follow-up.
研究者
Sue Yom
Principal Investigator
University of California, San Francisco
入排标准
入选标准
- •Males and females ≥18 years of age.
- •Histologically or cytologically confirmed nasopharyngeal carcinoma, stage II-IV by American Joint Committee on Cancer (AJCC) 7th edition, endemic-type (defined as World Health Organization (WHO) type 2a and 2b nonkeratinizing or undifferentiated subtypes, excluding WHO type I keratinizing subtype) performed on a biopsy that occurred within 90 days of registration.
- •Positron emission tomography-computed tomography (PET-CT) (preferred) or a CT of chest, abdomen, and pelvis within 60 days of registration showing radiographic stage II to IVB nasopharyngeal cancer.
- •No distant metastasis as verified by one of the study investigators.
- •Documentation that the patient is a candidate for chemoradiation of their nasopharyngeal cancer by one of the study investigators.
- •Ability to tolerate radiation therapy (e.g. lie flat and hold position for treatment).
- •Measurable disease as defined by RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Lack of contraindications to systemic immunotherapy (see list of exclusions below).
- •Resolution of all acute toxic effects of any prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE Version 5.0 grade
排除标准
- •Active second malignancy, i.e. patient known to have potentially fatal hematologic malignancy or another solid primary tumor present for which he/she may be (but not necessarily) currently receiving treatment. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are allowed to enroll in this trial. For example, patients with early-stage skin cancers, prostate cancer under surveillance with non-rising prostate-specific antigen (PSA), or meningioma or thyroid papillary cancers which are under surveillance are eligible. For determinations of a specific clinical condition, please consult with the Principal Investigator.
- •Active, untreated central nervous system (CNS) metastases;
- •Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2), anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways, or cancer vaccine;
- •Prior systemic cytotoxic therapy, antineoplastic biologic therapy, or major surgery within 28 days of first dose of study medication;
- •Severe hypersensitivity reaction to treatment during prior administration of a monoclonal antibody (mAb) or history of allergy to any study drug component;
- •Has received a live-virus vaccination within 30 days of planned treatment start;
- •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.
- •Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or pneumonitis requiring oral or IV glucocorticoids;
- •Active, known, or suspected autoimmune disease or any autoimmune condition that has required systemic treatment in the past 2 years (replacement therapies for hormone deficiencies are allowed); Subjects are 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.
- •Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation);
研究组 & 干预措施
Nivolumab + chemoradiation
Patients receive nivolumab IV over 60 minutes on day 1 of courses 1-5 and 7-12. Treatment repeats every 14 days for 11 courses in the absence of disease progression or unacceptable toxicity. Beginning at course 2, patients undergo radiation therapy QD 5 days per week and receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 7 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab
Nivolumab + chemoradiation
Patients receive nivolumab IV over 60 minutes on day 1 of courses 1-5 and 7-12. Treatment repeats every 14 days for 11 courses in the absence of disease progression or unacceptable toxicity. Beginning at course 2, patients undergo radiation therapy QD 5 days per week and receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 7 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin
Nivolumab + chemoradiation
Patients receive nivolumab IV over 60 minutes on day 1 of courses 1-5 and 7-12. Treatment repeats every 14 days for 11 courses in the absence of disease progression or unacceptable toxicity. Beginning at course 2, patients undergo radiation therapy QD 5 days per week and receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 7 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy
结局指标
主要结局
Rate of Completion of All Adjuvant Immunotherapy
时间窗: Up to 1 year
The rate of completion of all adjuvant therapy by patients treated at the maximum tolerated dose (MTD) schedule will be determined and compared to a historical control rate of 52%, the rate of completion of a standard adjuvant cisplatin-based platform to determine feasibility of study treatment
次要结局
- Overall Response Rate (ORR)(Up to 1 year after completion of treatment)
- Number of Treatment-related Adverse Events (AEs)(Up to 1 year after completion of treatment)
- Mean Loco-regional Control (LRC) Rate(Up to 1 year after completion of treatment)
- Mean Distant Metastasis (DM) Rate(Up to 1 year after completion of treatment)
- Mean Change in Scores on the Functional Assessment of Cancer Therapy - Nasopharyngeal Cancer (FACT-NP)(Up to 1 year after completion of treatment)
- Percentage of Participants With Acute Toxicities(Up to 1 year after completion of treatment)
- Percentage of Participants With Late Toxicities(Up to 1 year after completion of treatment)