A Phase II, Randomized, Multicenter Study to Assess the Efficacy of Nab-paclitaxel-based Doublet as First Line Therapy in Patients With Cancer of Unknown Primary (CUP): The AGNOSTOS Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 10
- 主要终点
- Objective response rate (ORR) as evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
研究概览
简要总结
Agnostos Trial is a multicentric phase 2 randomized trial with a 'pick-the-winner design' in chemonaive patients with cancer of unknown primary. It will assess the efficacy of the two best active single agent - carboplatin or gemcitabine - added to an innovative taxane back bone (nab-Paclitaxel). Agnostos trial is a part of a larger clinical and translational initiative to improve the outlook of patients with cancer of unknown primary through evaluation of novel chemotherapeutic regimens.
详细描述
Treatment-naïve patients with CUP diagnosis confirmed according to CUP Diagnostic Guidelines, will be enrolled into AGNOSTOS trial. Patients will be randomized upfront to receive a nab-paclitaxel-based duplet adding either carboplatin or gemcitabine until progression or unacceptable toxicity (randomization 1:1, n= 120; 60 per arm).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Provision of written informed consent.
- •Patients must be ≥ 18 years of age.
- •Diagnosis of CUP according to CUP Diagnostic Guidelines derived from ESMO 2011 and NCCN 2015 guidelines.
- •Sufficient archived biopsy tissue from a surgical or core needle biopsy required to perform the CUP multiplex assay.
- •Eastern Cooperative Oncology Group performance status ≤
- •No previous systemic therapy.
- •At least one measurable lesion by RECIST Criteria.
- •Good liver, cardiac, lung and marrow bone function.
- •Evidence of non-childbearing status for female patients: negative urine or serum pregnancy test within 21 days of study treatment for women of childbearing potential, or postmenopausal status.
- •Patients of child bearing potential and their partners, who are sexually active, must agree to the use of highly effective forms of contraception throughout their participation in the study.
- •Patient is willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations.
排除标准
- •Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, breast Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma.
- •Specific treatable CUP syndromes including: extragonadal germ cell syndrome; neuroendocrine carcinoma; adenocarcinoma isolated to axillary lymph nodes (women cancer); peritoneal carcinomatosis (women - ovarian cancer); squamous carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes; single resectable metastasis.
- •Patients receiving any radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry.
- •Patients with symptomatic uncontrolled brain metastases.
- •Major surgery within 2 weeks of starting the study and patients must have recovered from any effects of any major surgery.
- •Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
- •Pregnant or breast feeding women.
- •Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- •Patients with known hepatic disease (eg, Hepatitis B or C).
- •Previous cancer treatment.
- •Patients currently enrolled in another clinical tria, except AGNOSTOS PROFILING.
- •Patients that are receiving chemotherapy, hormonal therapy (HRT is acceptable) or other novel agents.
- •Patients receiving live virus and bacterial vaccines.
研究组 & 干预措施
Arm A
nab-paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes without premedication, followed by gemcitabine 1000 mg/m2 on Days 1 and 8 by IV administration over 30 minutes. Treatment to be repeated Q21 days.
干预措施: nab-paclitaxel (Drug)
Arm A
nab-paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes without premedication, followed by gemcitabine 1000 mg/m2 on Days 1 and 8 by IV administration over 30 minutes. Treatment to be repeated Q21 days.
干预措施: Gemcitabine (Drug)
Arm B
nab-paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes without premedication, followed by carboplatin AUC 2 on Day 1 and 8 by IV administration over 60 minutes. Treatment to be repeated Q21 days.
干预措施: nab-paclitaxel (Drug)
Arm B
nab-paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes without premedication, followed by carboplatin AUC 2 on Day 1 and 8 by IV administration over 60 minutes. Treatment to be repeated Q21 days.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Objective response rate (ORR) as evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
时间窗: 42 months
次要结局
- toxicity according to Common Terminology Criteria for Adverse Events - CTCAE version 4.03.(42 months)
- time to progression(42 months)
- duration of response according to RECIST version 1.1.(42 months)
- overall survival(42 months)