NCT02642809已完成1 期
A Pilot Study Combining Pembrolizumab With Locally Delivered Radiation Therapy for the Treatment of Metastatic Esophageal Cancers
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Safety as Measured by Number of Participants With Grade 3 or Higher Treatment Related Adverse Events
研究概览
简要总结
The investigators propose to treat patients with metastatic esophageal cancers and dysphagia with two fractions of brachytherapy followed by pembrolizumab. The brachytherapy is hypofractionated and will provide a radiation dose of sufficient intensity to induce the release of tumor-derived antigens and trigger an antitumor immune response. The simplicity of the design should maximize the chance to examine the hypothesis that radiotherapy can induce an immune response, which can then be augmented by pembrolizumab treatment. Success in this study would provide the impetus to conduct further trials aimed at developing this unique strategy as a more broadly applicable therapeutic option in the treatment of patients suffering from these deadly cancers, and will provide important mechanistic insights into the relationship between radiation treatment and immune therapy augmentation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any patient with metastatic esophageal cancer that is deemed a candidate for brachytherapy for local control or treatment of dysphagia as determined by treating physician
- •Presence of an evaluable metastatic lesion (locoregional lymph nodes are acceptable)
- •At least 18 years of age.
- •ECOG performance status 0-2
- •Adequate bone marrow and organ function as defined below:
- •Absolute neutrophil count ≥ 1,500/mcL
- •Platelets ≥ 100,000/mcL
- •Hemoglobin ≥ 9 g/dL
- •Total bilirubin ≤ 1.5 x IULN OR Direct bilirubin ≤ IULN for patients with total bilirubin > 1.5 x IULN
- •AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver metastases)
- •Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min/1.73 m2 for patients with creatinine levels > 1.5 x IULN
- •INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
- •aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of a anticoagulants
- •Sexually active women of childbearing potential and men must agree to use contraceptive methods prior to study entry, for the duration of study participation, and for 120 days after the last dose of pembrolizumab. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- •Either enrolled in HRPO# 201107221 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information for Patients with Gastrointestinal Cancers"), which facilitates the collection of specimens for correlative studies, or consenting to collection of blood and tissue as part of this protocol for research testing.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- •Received a live vaccine within 30 days prior to the first dose of pembrolizumab. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.
- •Currently receiving any other investigational agents, has participated in a study of an investigational agent, or use of an investigational device within 4 weeks of the first dose of pembrolizumab.
- •Has received systemic therapy within 4 weeks of the first dose of pembrolizumab.
- •Known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of MK-3475 and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or other agents used in the study.
- •Uncontrolled intercurrent illness that would limit compliance with study requirements. This would include, but is not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, underlying pulmonary disease, or psychiatric illness/social situations.
- •Has an active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 72 hours of study entry.
- •Known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected).
- •Known history of active TB.
- •Known history of HIV (HIV 1/2 antibodies).
研究组 & 干预措施
Pembrolizumab and Brachytherapy
Experimental
- Brachytherapy dose=16 Gy delivered in 2 fractions of 8 Gy per fraction, separated by 7-10 days between fractions.
- Pembrolizumab started within 1 week after completion of brachytherapy administered as an intravenous infusion with a dose of 200 mg. It will be given every 3 weeks.
- Research endoscopic biopsy for 8 consented patients will take place 1-2 weeks after initiation of brachytherapy.
干预措施: Pembrolizumab (Drug)
Pembrolizumab and Brachytherapy
Experimental
- Brachytherapy dose=16 Gy delivered in 2 fractions of 8 Gy per fraction, separated by 7-10 days between fractions.
- Pembrolizumab started within 1 week after completion of brachytherapy administered as an intravenous infusion with a dose of 200 mg. It will be given every 3 weeks.
- Research endoscopic biopsy for 8 consented patients will take place 1-2 weeks after initiation of brachytherapy.
干预措施: Brachytherapy (Radiation)
结局指标
主要结局
Safety as Measured by Number of Participants With Grade 3 or Higher Treatment Related Adverse Events
时间窗: Through 30 days after completion of treatment (median length of adverse event follow-up 106 days, full range 42-1023 days)
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 will be utilized for all toxicity reporting. In general, CTCAE version 4.03 has the following definitions for the grading scale: Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
次要结局
- Mean Percent Change in Esophageal Tumor Length as Measured by Endoscopy(Prior to brachytherapy and once anytime between 2-6 months after start of pembrolizumab (up to approximately 7 months post-baseline))
- Change in Esophageal Lumen Size as Measured by Endoscopy(Prior to brachytherapy, at 1-2 weeks after initiation of brachytherapy (optional), and 2-6 months after start of pembrolizumab)
- Worst Grade of Dysphagia Experienced by Participant(From start of treatment through 8 weeks post-pembrolizumab (median length of dysphagia follow-up 132 days, full range 42-1049 days))
- Overall Response as Measured by Immune-Related Response Criteria (irRC)(Through completion of treatment (median length of treatment 76 days, full range 25-993 days))
- Median Progression-free Survival (PFS)(Up to 1 year after completion of treatment (median length of treatment 76 days, full range 25-993 days))
- Median Overall Survival (OS)(Up to 1 year after completion of treatment (median length of treatment 76 days, full range 25-993 days))
研究者
研究点 (1)
Loading locations...
相似试验
已完成
2 期
Pembrolizumab in Refractory Advanced Esophageal CancerSquamous Cell Esophagus CancerAdenocarcinoma EsophagusEsophageal CancerNCT02971956Dana-Farber Cancer Institute49
已完成
早期 1 期
Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal AdenocarcinomaAdvanced Gastroesophageal Junction AdenocarcinomaClinical Stage III Esophageal Adenocarcinoma AJCC v8Clinical Stage III Gastric Cancer AJCC v8Clinical Stage IV Esophageal Adenocarcinoma AJCC v8Clinical Stage IV Gastric Cancer AJCC v8Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8Clinical Stage IVA Gastric Cancer AJCC v8Clinical Stage IVB Esophageal Adenocarcinoma AJCC v8Clinical Stage IVB Gastric Cancer AJCC v8Gastroesophageal Junction AdenocarcinomaMetastatic Gastroesophageal Junction AdenocarcinomaPathologic Stage III Esophageal Adenocarcinoma AJCC v8Pathologic Stage III Gastric Cancer AJCC v8Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8Pathologic Stage IIIA Gastric Cancer AJCC v8Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8Pathologic Stage IIIB Gastric Cancer AJCC v8Pathologic Stage IIIC Gastric Cancer AJCC v8Pathologic Stage IV Esophageal Adenocarcinoma AJCC v8Pathologic Stage IV Gastric Cancer AJCC v8Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8Pathologic Stage IVB Esophageal Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage III Gastric Cancer AJCC v8Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8Unresectable Gastroesophageal Junction AdenocarcinomaNCT03395847M.D. Anderson Cancer Center9
尚未招募
3 期
Safety and Efficacy of Pembrolizumab in Combination With FLOT About Gastroesophageal Junction Cancer:Gastroesophageal Junction CancerNCT06411171xiaohua li36
已完成
1 期
A Study Of Pembrolizumab In Combination With Trastuzumab-DM1Breast CancerNCT03032107Dana-Farber Cancer Institute20
暂停
2 期
Pembrolizumab in Neoplasms or LymphomasHistiocytic SarcomaInterdigitating Dendritic Cell SarcomaLymphomaFollicular Dendritic Cell SarcomaNCT03316573Dana-Farber Cancer Institute18