IMRT Followed by Pembrolizumab in the Adjuvant Setting in Anaplastic Cancer of the Thyroid (IMPAACT): Phase II Trial Adjuvant Pembrolizumab After IMRT in ATC
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Median Progression-free Survival (PFS) in Stage IVB ATC Patients With Gross Disease Treated With External Beam Radiation Followed by Adjuvant Pembrolizumab
研究概览
简要总结
This is an open label, single center, phase 2 trial of adjuvant pembrolizumab after external beam radiation to the primary tumor in patients with stage IVB (disease localized to the neck) ATC. This drug trial will estimate the median progression-free survival (PFS) (from the start of adjuvant pembrolizumab until locoregional progression, development of distant metastatic disease, or death) in stage IVB ATC patients with gross disease, treated with external beam radiation (+/- concomitant chemotherapy) followed by adjuvant pembrolizumab. Patients will be patients enrolled from cohort 1 and 2 (cohort 1: ≥51 Gy; cohort 2: ≤50 Gy).
详细描述
Primary Objective:
-To estimate the median progression-free survival (PFS) (from the start of adjuvant pembrolizumab until locoregional progression, development of distant metastatic disease, or death) in stage IVB ATC patients with gross disease, treated with external beam radiation (+/- concomitant chemotherapy) followed by adjuvant pembrolizumab. Patients will be patients enrolled from cohort 1 and 2 (cohort 1: ≥51 Gy; cohort 2: ≤50 Gy).
Secondary Objective:
-To estimate median overall survival in stage IVB ATC patients treated with external beam radiation (+/- concurrent chemotherapy) followed by adjuvant pembrolizumab. Patients will be stratified by dose of external beam radiation.
Exploratory Objective:
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
- •Male/female participants who are at least 18 years of age on the day of signing informed consent with Pathologic findings supporting the clinical impression of anaplastic thyroid carcinoma will be enrolled in this study. Diagnosis may include consistent with or suggestive of terminology associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present.
- •Stage IVB disease (no convincing evidence of metastatic disease outside of the neck) who have unresectable disease are eligible in groups 1 or
- •Previous excisional biopsy is permitted.
- •Stage IVB disease (no convincing evidence of metastatic disease outside of the neck) who have undergone complete resection of tumor (no convincing evidence of metastatic disease in the neck) are eligible in group 3
- •Patient must have completed external beam radiation with or without concomitant cytotoxic chemotherapy to participate in groups 1 and
- •Those who have completed these treatment after surgical resection of primary tumor may participate in group
- •Patients may enroll only after completing radiation. Study drug may start from 2-6 weeks (+2 weeks) after radiation is completed and can only be started once radiation and chemotherapy-related toxicities are grade 2 or less (with the exception of alopecia). If a subject is consented but AEs are not grade 2 or less by 8 weeks after RT is completed, that subject is not eligible and should not start pembrolizumab.
- •A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
- •Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
- •A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
- •A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 32 weeks (5 terminal half-lives for pembrolizumab plus an additional 90 days) from the last dose of study treatment and refrain from donating sperm during this period.
- •The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
- •Adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study intervention.
排除标准
- •A WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of pembrolizumab (see Appendix 3). A serum pregnancy test will be required.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- •Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- •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 study drug.
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease, not related to radiation.
- •Has an active infection requiring systemic therapy.
- •Has a known history of Human Immunodeficiency Virus (HIV) infection.
- •Has a 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) infection.
研究组 & 干预措施
Pembrolizumab
The infusions are given every 6 weeks
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Median Progression-free Survival (PFS) in Stage IVB ATC Patients With Gross Disease Treated With External Beam Radiation Followed by Adjuvant Pembrolizumab
时间窗: From the start of adjuvant pembrolizumab until disease progression or death
To estimate the median progression-free survival (PFS) (from the start of adjuvant pembrolizumab until locoregional progression, development of distant metastatic disease, or death) in stage IVB ATC patients with gross disease, treated with external beam radiation (+/- concomitant chemotherapy) followed by adjuvant pembrolizumab. Patients will be patients enrolled from cohort 1 and 2 cohort 1: \>51 Gy; cohort 2: \<50 Gy).
Median Overall Survival (OS) in Stage IVB ATC Patients Treated With External Beam Radiation Followed by Adjuvant Pembrolizumab
时间窗: From the start of adjuvant pembrolizumab until disease progression or death
To estimate median overall survival in stage IVB ATC patients treated with external beam radiation (+/- concurrent chemotherapy) followed by adjuvant pembrolizumab. Patients will be stratified by dose of external beam radiation.
次要结局
未报告次要终点