A Phase II Study Evaluating Safety and Efficacy of Durvalumab (MEDI4736) Following Multi-modality Therapy in Esophageal Cancer: Big Ten Cancer Research Consortium BTCRC-ESO14-012
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 39
- 试验地点
- 3
- 主要终点
- Percentage of Participants With One-Year Relapse Free Survival (RFS) With Post-Operative Durvalumab
研究概览
简要总结
This is a phase II, open-label, single arm, single-stage study. A total of 23 evaluable patients will be enrolled. If total number of patients free of disease relapse at 1 year is less than or equal to 15, the drug would not be considered for further study in this setting. After six patients are treated with at least one dose of study drug, they will be observed for a minimum of 60 days. During the 60-day observation period, further accrual will be halted to evaluate "unacceptable toxicities warranting early closure of the trial" defined as:
- Any definitive durvalumab-related death. A durvalumab-related death will be continuously monitored throughout the trial and the trial will be suspended for re-evaluation whenever such an event is confirmed.
- Any unexpected and previously unreported grade 4 toxicities definitely related to durvalumab.
详细描述
OUTLINE: This is a multi-center trial.
INVESTIGATIONAL TREATMENT:
Subjects will receive durvalumab 1500 mg IV every 4 weeks (1 cycle) for a maximum 13 doses (12 months), or until unacceptable toxicities or disease recurrence.
The following baseline labs must be completed within 28 days prior to registration for protocol therapy:
Hematopoietic:
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
盲法说明
Open Label
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
- •Subject must meet all of the following applicable inclusion criteria to participate in this study:
- •Written informed consent and HIPAA authorization for release of protected health information obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of 0-1 within 28 days prior to registration for protocol therapy.
- •Females of childbearing potential and males must be willing to use two effective methods of contraception (see the protocol) from the time consent is signed until 3 months after treatment discontinuation.
- •Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration for protocol therapy. NOTE: Female subjects are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are ≥60 years old and naturally postmenopausal for at least 12 consecutive months. See the protocol.
- •Histological evidence of persistent residual esophageal adenocarcinoma including gastroesophageal junction adenocarcinoma following definitive concurrent chemoradiotherapy (carboplatin and paclitaxel or cisplatin and 5-FU) in the surgical sample (esophagus or lymph node or both) obtained at the time of esophagectomy. NOTE: Persistent residual disease is defined as follows (modified from College of American Pathologists Guidelines):
- •No residual tumor (Grade 0, complete response, 0% tumor). This group will not be included in this study.
- •Marked response (Grade 1, 0-<10% residual tumor)
- •Moderate response (Grade 2, 10-50% residual tumor)
- •No definite response (Grade 3, >50% residual tumor)
- •Minimum of 1 month and maximum of 3 months from surgical resection with no evidence of disease progression at the time of enrollment.
- •Must have adequately recovered from surgery as judged by the treating investigator.
- •Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
排除标准
- •Subjects meeting any of the criteria below may not participate in the study:
- •Prior therapy with a PD-1, PD-L1, or CTLA-4 inhibitor or cancer-specific vaccine therapy.
- •Evidence of active autoimmune disease requiring systemic treatment within preceding 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions to this rule include vitiligo, resolved childhood asthma/atopy, requirement of intermittent bronchodilators or local steroid injections, hypothyroidism stable on hormone replacement, psoriasis not requiring systemic treatment (within the past 2 years), Graves's disease and Sjogren's syndrome.
- •Prior malignancy is not allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason score ≤ 7 prostate cancers, or other cancer for which the subject has been disease-free for at least 3 years.
- •Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis).
- •Presence of interstitial lung disease or history of pneumonitis requiring treatment with corticosteroids.
- •Patients with diagnosis of primary immunodeficiency.
- •Patients receiving chronic systemic corticosteroid therapy or other immunosuppressive therapy within 28 days prior to registration for protocol therapy. Exceptions include intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
- •History of allogeneic organ or stem cell transplant.
- •Receipt of live attenuated vaccine within 30 days prior to registration for protocol therapy.
- •Mean QT interval corrected for heart rate (QTc) > 470 msec calculated from 3 ECGs by Bazett's Correction.
- •Ventricular arrhythmias requiring medication(s).
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or active bleeding diatheses.
- •History of psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
- •Known HIV infection or chronic hepatitis B or C.
- •Known history of previous clinical diagnosis of tuberculosis.
- •Clinically significant infections as judged by the treating investigator. Clinically significant is defined as an active infection requiring IV antibiotics.
- •Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued. In addition, breast milk cannot be stored for future use while the mother is being treated on study.
- •Treatment with any investigational agent within 28 days prior to registration for protocol therapy.
- •History of hypersensitivity to durvalumab or any excipient.
- •Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
- •Previous enrollment in the present study.
研究组 & 干预措施
Investigational Treatment
Durvalumab 1500 mg IV every 4 weeks (1 cycle) for a maximum 13 doses (12 months), or until unacceptable toxicities or disease recurrence.
干预措施: Durvalumab (Drug)
结局指标
主要结局
Percentage of Participants With One-Year Relapse Free Survival (RFS) With Post-Operative Durvalumab
时间窗: From the date of surgery until disease relapse or death up to a maximum of 40 months.
Relapse free survival is defined as time from the date of surgery until the criteria for disease relapse is met, per Response Evaluation Criteria In Solid Tumors (RECIST 1.1), or death occurs. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started The percentage of subjects who attained relapse free survival for 1 year and 95 % confidence interval has been reported here.
次要结局
- Number of Patients With Adverse Events as a Measure of Safety and Tolerability(From the time of consent until 90 days after last dose of durvalumab up to a maximum of 15 months.)
研究者
Shadia Jalal, MD
Sponsor-Investigator
Big Ten Cancer Research Consortium