NCT05518110终止2 期
PaTcH Trial: A Phase 2 Study to Explore Primary and Emerging Resistance Mechanisms in Patients With Metastatic Refractory Pancreatic Cancer Treated With Trametinib and Hydroxychloroquine
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Patients free of disease progression
研究概览
简要总结
This study is designed to investigate the means by which cancer resists treatment can be overcome by a combination of an established anticancer drug, trametinib, with hydroxychloroquine.
详细描述
The study is a multi-centre single arm Phase 2 clinical trial to explore primary and emerging resistance mechanisms in patients with metastatic refractory pancreatic cancer treated with trametinib and hydroxychloroquine. This study will include 10-22 patients with metastatic pancreatic cancer who have previously progressed on at least one line of systemic therapy.
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
- •Each patient must meet all of the following inclusion criteria to be eligible for the study:
- •Patients must have pathologically confirmed advanced metastatic pancreatic adenocarcinoma or poorly differentiated pancreatic adenocarcinoma that is amenable to tumour biopsy.
- •Patients have received at least one line of systemic therapy for metastatic disease and not be amenable to surgical resection.
- •Patients must have measurable disease by RECIST 1.1 criteria.
- •Age ≥18 years.
- •ECOG performance status ≤ 1
- •Patients must have normal organ and marrow function as defined below:
- •Serum creatinine ≤ 1.5 x ULN.
- •Adequate hepatic function defined by:
- •total bilirubin level ≤ 1.5 × ULN,
- •an AST, level ≤ 2.5 × ULN, and an ALT level ≤ 2.5 × ULN (or, for subjects with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN)
- •Hematological eligibility parameters:
- •Absolute Neutrophil count ≥ 1.5 x 109/L
- •Platelet count ≥100 x109/L
- •Hemoglobin ≥ 9 g/dL
- •Ability of subject to understand and the willingness to sign a written informed consent document.
- •Women of child-bearing potential or sexually active males must agree to use highly effective contraceptive measures. This applies from starting treatment until at least 16 weeks after the last study drug administration. The investigator or a designated associate is required to advise the patient how to achieve an adequate birth control. Highly effective contraception is defined in the study as methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include:
- •I. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal). II. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable and implantable). III. Intrauterine device (IUD). IV. Intrauterine hormone-releasing system (IUS). V. Bilateral tubal occlusion. VI. Successfully vasectomised partner. VII. Sexual abstinence.
排除标准
- •Patients are excluded from the study if any of the following exclusion criteria apply:
- •Persisting toxicity related to prior therapy (CTCAE Grade > 1); however alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
- •Prior treatment with a MEK inhibitor
- •Known history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome.
- •Any significant disease that, in the opinion of the investigator, may impair the patient's tolerance of study treatment.
- •Patients who are receiving any other investigational agents within 28 days before start of study treatment.
- •Prior organ transplantation including allogenic stem-cell transplantation.
- •Patients with known central nervous system metastases.
- •Active uncontrolled infection, requiring systemic therapy.
- •Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- •Severe left ventricular dysfunction as defined by ejection fraction < 45%
- •Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- •Known maculopathy of the eye
- •Known history or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
- •Screening corrected QT interval by Fridericia (QTcF) > 500 msec
- •Pregnant women and breastfeeding mothers are excluded due to unknown impact on embryos or infants
- •Known prior severe hypersensitivity to investigational products or any component in its formulation.
- •Concurrent use of medicines known to induce retinal toxicity (e.g. tamoxifen) or QT interval prolonging agents.
- •Known congenital or documented acquired QT prolongation.
- •Uncorrected hypokalemia and/or hypomagnesemia.
研究组 & 干预措施
PaTcH
Experimental
All eligible patients will be treated with trametinib 2mg and hydroxychloroquine 1200mg daily (600mg twice a day (BID)) orally. Treatment will be continuous in treatment cycles lasting 28 days, and will continue until radiological or clinical progression of disease, unacceptable toxicity or consent withdrawal.
干预措施: Trametinib (Drug)
PaTcH
Experimental
All eligible patients will be treated with trametinib 2mg and hydroxychloroquine 1200mg daily (600mg twice a day (BID)) orally. Treatment will be continuous in treatment cycles lasting 28 days, and will continue until radiological or clinical progression of disease, unacceptable toxicity or consent withdrawal.
干预措施: Hydroxychloroquine (Drug)
结局指标
主要结局
Patients free of disease progression
时间窗: Twelve weeks from starting treatment.
The percentage of patients free of disease progression at 12 weeks from starting treatment into the study as determined by radiographic disease assessments per RECIST version 1.1.
次要结局
- Overall Survival(Through study completion, an average of five years)
- Safety and tolerability(Through study treatment, an average of one year)
- Tumour Response Rate(Twelve weeks following the 15th and 22nd patients.)
- Duration of Response(Through study treatment, an average of 1 year)
研究者
研究点 (2)
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