A Phase 1/2 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy of KRC-01 Intratumoral Injection Combined With Radiotherapy in Patients With Locally Advanced Cervical Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Kortuc, Inc.
- 入组人数
- 70
- 试验地点
- 9
- 主要终点
- AEs of special interest
研究概览
简要总结
This is a seamless Phase 1/2 study consisting of two components. Phase 1 component is a dose-escalation, single arm, open label study in 10 patients to evaluate the safety and tolerability of KRC 01. Phase 2 component is a randomized, open label, controlled, multi-center study in 60 patients to evaluate the preliminary antitumor effect of KRC-01 in combination with CRT.
详细描述
This is a seamless Phase 1/2 study consisting of two components. Phase 1 component is a dose-escalation, single arm, open label study in 10 patients to evaluate the safety and tolerability of KRC 01. Phase 2 component is a randomized, open label, controlled, multi-center study in 60 patients to evaluate the preliminary antitumor effect of KRC-01 in combination with CRT.
Phase 1 component (n=10) Phase 1 component is a dose-escalation single arm, open label study. All eligible subjects will receive external beam radiotherapy (EBRT) with cisplatin (40 mg/m2) intravenously (IV) once weekly for 5 weeks (sixth dose optional) followed by image-guided brachytherapy (BT).
KRC-01 will be dosed intratumorally within 2 hours prior to EBRT starting from second week of EBRT.
There are two cohorts (n=5 per cohort) Cohort 1: Once-a-week between Monday to Thursday (not necessarily the same day every week) Cohort 2: Twice-a-week with a 1- or 2- day interval (either Mon+Wed, Mon+Thu, or Tue+Thu)
After 5 subjects of Cohort 1 have completed CRT+BT, the safety review committee (SRC) will evaluate the safety and tolerability of KRC-01 once-a-week dosing and determine Go/ No Go decision to Cohort 2 (twice-a-week dosing).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent before participation.
- •Female subjects age 18 years or older.
- •Histologically diagnosed squamous cell carcinoma, adenocarcinoma or adeno-squamous cell carcinoma of the uterine cervix.
- •FIGO stage II and III locally advanced cervical cancer.
- •No evidence of metastatic disease.
- •At least one tumor that qualifies as a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 tumor with tumor size >5 cm diameter, not previously irradiated, at baseline assessed [by magnetic resonance imaging (MRI)] within 28 days before Day
- •No prior chemotherapy or radiotherapy for cervical cancer.
- •Intention to undergo treatment including EBRT with 5 cycles of cisplatin followed by BT; to be completed within 8 weeks of its initiation.
- •Patients with predicted life expectancy of 3 months or more.
- •Target tumor is accessible for intratumoral injection.
- •Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or
- •Negative pregnancy test before start of CRT in women of childbearing potential and an ability/willingness to protect against pregnancy from consent and for 3 months post-RT.
排除标准
- •Other primary malignancies except basal cell carcinoma of the skin.
- •Histologically diagnosed small cell (neuroendocrine), melanoma, clear cell and other rare variants of the classical adenocarcinoma at cervices.
- •Previous pelvic or abdominal radiotherapy.
- •Previous total or partial hysterectomy.
- •Combination of preoperative radiotherapy with surgery.
- •Patients receiving neo-adjuvant chemotherapy or non-protocol antineoplastic treatment apart from weekly cisplatin (40 mg/m2).
- •Anatomical location and/or extent of disease difficult to access for safe intratumoral drug injections.
- •Contraindications to the pelvic radiation such as inflammatory bowel disease and collagen vascular disease.
- •Contraindications to MRI.
- •Patients on anticoagulants or deranged coagulation profile.
- •Pregnancy or nursing.
- •High medical risks because of non-malignant systemic disease or with active uncontrolled infection.
- •Participation in another clinical trial with an investigational drug, device or biologic within the preceding 3 months, except an observational study.
研究组 & 干预措施
dose-escalation single arm
Dose-escalation single arm, open label study. All eligible subjects will receive external beam radiotherapy (EBRT) with cisplatin (40 mg/m2) intravenously (IV) once weekly for 5 weeks (sixth dose optional) followed by image-guided brachytherapy (BT).
KRC-01 will be dosed intratumorally within 2 hours prior to EBRT starting from second week of EBRT.
There are two cohorts (n=5 per cohort) Cohort 1: Once-a-week between Monday to Thursday (not necessarily the same day every week) Cohort 2: Twice-a-week with a 1- or 2- day interval (either Mon+Wed, Mon+Thu, or Tue+Thu)
干预措施: KRC-01 (Drug)
dose-escalation single arm
Dose-escalation single arm, open label study. All eligible subjects will receive external beam radiotherapy (EBRT) with cisplatin (40 mg/m2) intravenously (IV) once weekly for 5 weeks (sixth dose optional) followed by image-guided brachytherapy (BT).
KRC-01 will be dosed intratumorally within 2 hours prior to EBRT starting from second week of EBRT.
There are two cohorts (n=5 per cohort) Cohort 1: Once-a-week between Monday to Thursday (not necessarily the same day every week) Cohort 2: Twice-a-week with a 1- or 2- day interval (either Mon+Wed, Mon+Thu, or Tue+Thu)
干预措施: brachytherapy (Radiation)
dose-escalation single arm
Dose-escalation single arm, open label study. All eligible subjects will receive external beam radiotherapy (EBRT) with cisplatin (40 mg/m2) intravenously (IV) once weekly for 5 weeks (sixth dose optional) followed by image-guided brachytherapy (BT).
KRC-01 will be dosed intratumorally within 2 hours prior to EBRT starting from second week of EBRT.
There are two cohorts (n=5 per cohort) Cohort 1: Once-a-week between Monday to Thursday (not necessarily the same day every week) Cohort 2: Twice-a-week with a 1- or 2- day interval (either Mon+Wed, Mon+Thu, or Tue+Thu)
干预措施: External Beam Radiation Therapy (Radiation)
dose-escalation single arm
Dose-escalation single arm, open label study. All eligible subjects will receive external beam radiotherapy (EBRT) with cisplatin (40 mg/m2) intravenously (IV) once weekly for 5 weeks (sixth dose optional) followed by image-guided brachytherapy (BT).
KRC-01 will be dosed intratumorally within 2 hours prior to EBRT starting from second week of EBRT.
There are two cohorts (n=5 per cohort) Cohort 1: Once-a-week between Monday to Thursday (not necessarily the same day every week) Cohort 2: Twice-a-week with a 1- or 2- day interval (either Mon+Wed, Mon+Thu, or Tue+Thu)
干预措施: cisplatin (Drug)
结局指标
主要结局
AEs of special interest
时间窗: 36 month
(local pain, radiation dermatitis, tumor lysis syndrome, superficial soft tissue fibrosis, vaginal stenosis, gastrointestinal/urinary AEs, and severe and medically significant bleeding (requires urgent intervention) after intratumoral injection)
Tolerance
时间窗: week 1 to 6
• Number of patients who have a significant treatment delays/interruption (total duration \> 59 days)
Adverse Events
时间窗: 36 month
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a study drug that does not necessarily have a causal relationship with the treatment.
Physical examination
时间窗: at the time of Screening and at Week 6 and partial examination will be done weekly in between to document relevant changes.
The physical examination will include: * General appearance * Head, eyes, ears, nose, and throat * Respiratory * Cardiovascular * Musculoskeletal * Abdomen * Neurologic * Extremities * Dermatologic * Lymphatic Partial examination, patient will verbally report changes since last week.
次要结局
- Progression-free survival(: minimum 2 years, maximum 3 years)
- Overall survival(minimum 2 years, maximum 3 years)
- Health-related quality of life (QOL)(minimum 2 years, maximum 3 years)
- Disease-free survival(minimum 2 years, maximum 3 years)