A Phase II Trial of CUDC-907 in Patients With Metastatic and Locally Advanced Thyroid Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
研究概览
简要总结
Background:
The thyroid is a gland at the base of the throat. Thyroid cancer is a disease that people get when abnormal cells begin to grow in this gland. Researchers believe a new drug called CUDC-907 may be able to help people with thyroid cancer that has spread or has gotten worse.
Objective:
To see if CUDC-907 will shrink tumors in people with advanced thyroid cancer.
Eligibility:
People at least 18 years old who have been diagnosed with locally advanced and metastatic thyroid cancer.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Electrocardiogram (ECG) heart test.
Review of their symptoms and how they perform normal activities
A scan will be performed. Some will have a computed tomographic scan (CT) that takes pictures of the body using a small amount of radiation. Some will have magnetic resonance imaging (MRI) that uses a magnetic field to take pictures.
Bone scan (some participants)
Fludeoxyglucose (FDG) positron emission tomography (PET) scan to produce a tumor image.
A sample of their tumor from a previous surgery. They may have a biopsy of their tumor if a tumor sample is not available from a previous surgery.
Participants will be given CUDC-907 in tablet form. They will take it by mouth once a day for 5 days, then take 2 days off, each week.
While taking the study drug, participants will have study visits that repeat the screening tests.
After they stop treatment, participants will have 3 follow-up visits over a year. They will repeat some tests. Then participants will be contacted by phone or e-mail every 6 months....
详细描述
Background:
- There are no standard or effective systemic therapies for metastatic or locally advanced poorly differentiated and undifferentiated thyroid cancer.
- Poorly differentiated and undifferentiated thyroid cancer are aggressive, with high mortality.
- CUDC-907 is a first-in-class dual inhibitor of histone deacetylase (HDAC) and PI3K signaling.
- Approximately 80% of poorly differentiated and undifferentiated thyroid cancers have driver mutations in the PI3K/AKT pathway or activation of the pathway.
- HDAC2 is upregulated in poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer, and CUDC-907 treatment reduces HDAC2 levels in thyroid cancer cells.
- CUDC-907 inhibits thyroid cancer cell growth, invasion and migration in vitro.
- In addition to inhibiting the PI3K/AKT signaling pathway, CUDC-907 inhibits the EGFR/RAS/RAF/MEK/ERK signaling pathway, which is also activated in poorly differentiated and undifferentiated thyroid cancer.
- CUDC-907 inhibits growth and metastases in a mouse model of metastatic thyroid cancer.
- We hypothesize that CUDC-907 will cause cancer regression in patients with metastatic and locally advanced poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer.
Objective:
-To determine response to CUDC-907 treatment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with locally advanced and metastatic poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer.
Eligibility:
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group
CUDC-907 for thyroid cancer
干预措施: CUDC-907 (Drug)
结局指标
主要结局
Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
时间窗: Approximately 6 months
Clinical response, defined as a complete response + partial response (CR+PR) to CUDC-907 treatment, was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
次要结局
- Median Amount of Time Subject Survives After Therapy(Approximately 12 months)
- Correlation Between Activation of the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) and EGFR/RAS/RAF/MEK/ERK Pathways in Tumor Tissue and Median Amount of Time Subject Survives Without Disease Progression After Treatment(At disease progression)
- Correlation Between Histone Deacetylase 2 (HDAC2) and Survivin Protein Levels in Tumor Tissue With Median Amount of Time Subject Survives Without Disease Progression After Treatment(At disease progression)
- Correlation Between Mutation Status of Tumor and Median Amount of Time Subject Survives Without Disease Progression After Treatment(At disease progression)
- Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)(Date treatment consent signed to date off study, approximately 12 months and 13 days)
- Median Amount of Time Subject Survives Without Disease Progression After Treatment(Approximately 6 months)
研究者
Naris Nilubol, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)