2024-516802-43-00招募中1/2 期
A Phase 1b/2 study of arfolitixorin combined with 5-fluorouracil, oxaliplatin, and bevacizumab in first-line treatment of metastatic colorectal cancer
相关药物
试验速览
- 阶段
- 1/2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Phase 1b and Phase 2: Number and severity of AEs, including clinically significant abnormal laboratory findings, regardless of causal relationship to ARFOX + bevacizumab. The outcome of Phase 1b is to determine the MTD of arfolitixorin (ARFOX + bevacizumab) in patients with mCRC.
研究概览
简要总结
Phase 1b:
- To evaluate the safety and tolerability of arfolitixorin, 5-FU, and oxaliplatin (ARFOX) + bevacizumab in patients with metastatic colorectal cancer (mCRC).
Phase 2:
- To evaluate the safety and tolerability of 2 pre-defined doses of arfolitixorin (maximum tolerated dose [MTD] and a dose level below MTD; ARFOX + bevacizumab) in patients with mCRC.
- To assess the anti-tumor activity of arfolitixorin (MTD and a dose level below MTD; ARFOX + bevacizumab) in patients with mCRC, in terms of ORR.
研究设计
- 分配方式
- Randomized
- 主要目的
- Part II: Phase 2 (dose optimization)
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Signed Informed Consent Form (ICF) and ability to comply with protocol requirements.
- •Life expectancy of >12 weeks.
- •Female patients must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test at screening, on a serum or urine sample obtained within 7 days prior to initiation of study treatment.
- •Female patients of childbearing potential must agree to use adequate contraceptive measures.
- •Male patients with female partners of childbearing potential must agree to use adequate contraceptive measures.
- •Histologically confirmed RAS mutant, microsatellite stable (MSS)/proficient mismatch repair (pMMR), colorectal adenocarcinoma with metastatic disease, eligible for first-line therapy with 5-FU, oxaliplatin, and bevacizumab regimen.
- •Tumor specimen (formalin-fixed, paraffin-embedded [FFPE]) available.
- •Adequate heart function as defined as: a) Heart rate ≤100 bpm. b) Blood pressure ≤140/
- •c) QTc interval ≤430 ms (males) or ≤450 ms (females). d) Ejection fraction (EF) >50%.
- •Acceptable hematologic laboratory values defined as: a) Hemoglobin ≥90 g/L. b) Absolute neutrophil count ≥1.5 × 109/L. c) Platelets ≥100 × 109/L.
- •Adequate organ function as defined by the following laboratory values: a) Total serum bilirubin ≤1.5 × upper limit of normal (ULN). b) Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 × ULN (≤5 × ULN in case of hepatic metastases). c) Creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min (as measured according to Cockcroft-Gault equation).
- •Age ≥18 years at the time of signing the ICF.
- •Radiographically measurable disease per RECIST (version 1.1) within 28 days of treatment allocation.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •Indication for any mCRC surgery or anti-cancer treatment other than study treatment, including but not limited to resection.
- •Current evidence of any condition that makes participating in this study not in the best interest of the patient, including, but not limited to: a) Myocardial infarction or unstable angina within the past 6 months. b) New York Heart Association (NYHA) Class II or greater cardiac disease. c) Congestive heart failure. d) QT prolongation syndrome >430 ms (females) and >450 ms (males). e) Serious arrhythmias requiring medication for treatment. f) Active infection requiring intravenous (i.v.) antibiotics. g) Ongoing drug or alcohol abuse.
- •Sensory peripheral neuropathy Grade ≥
- •Pregnancy or lactation.
- •Any medical condition, which in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities, or any psychological, familial, sociological or geographical condition that potentially hampers compliance with the study protocol and follow-up schedule.
- •Concomitant malignancies or previous malignancies with less than a 2-year disease-free interval at the time of signing consent. Patients with adequately treated basal or squamous cell carcinoma of the skin, or adequately treated carcinoma in situ (e.g., cervix) may enroll irrespective of the time of diagnosis. Patients with controlled, advanced prostate cancer are permitted. Ongoing adjuvant antihormonal therapy after breast or prostate cancer is permitted.
- •Prior 5-FU, oxaliplatin or bevacizumab administration for mCRC. Or more than 6 cycles (3 months) of oxaliplatin exposure during adjuvant treatment.
- •Known history of central nervous system (CNS) metastases or carcinomatous meningitis.
- •Receipt of any investigational product within 14 days or 5 half-lives prior to study treatment initiation, whichever is shortest. Note that participation in any other clinical study is not allowed as long as the patient is on study treatment.
- •Prior exposure to arfolitixorin.
- •Major surgery, or significant traumatic injury within 8 weeks of study treatment initiation.
- •Hypersensitivity to 5-FU, oxaliplatin or other platinum agent, or bevacizumab or to their excipients.
- •Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency test with a Clinical Pharmacogenetics Implementation Consortium (CPIC) activity score <1.
结局指标
主要结局
Phase 1b and Phase 2: Number and severity of AEs, including clinically significant abnormal laboratory findings, regardless of causal relationship to ARFOX + bevacizumab. The outcome of Phase 1b is to determine the MTD of arfolitixorin (ARFOX + bevacizumab) in patients with mCRC.
Phase 1b and Phase 2: Number and severity of AEs, including clinically significant abnormal laboratory findings, regardless of causal relationship to ARFOX + bevacizumab. The outcome of Phase 1b is to determine the MTD of arfolitixorin (ARFOX + bevacizumab) in patients with mCRC.
Phase 2: ORR, defined as the proportion of patients who have BOR of CR, or PR, measured from the start of the study treatment until the EOT by RECIST (version 1.1).
Phase 2: ORR, defined as the proportion of patients who have BOR of CR, or PR, measured from the start of the study treatment until the EOT by RECIST (version 1.1).
次要结局
- Phase 1b: ORR, defined as the proportion of patients who have BOR of CR, or PR, measured from the start of the study treatment until the EOT by RECIST (version 1.1).
- Phase 1b and Phase 2: PFS, defined as the time from the first study dose date to the date of first documentation of confirmed disease progression or death (whichever occurs first).
- Phase 1b and Phase 2: OS, measured from the date of study treatment initiation to the date of death.
- Phase 1b: Plasma concentration of arfolitixorin.
研究者
Sponsor Information Desk
Scientific
Isofol Medical AB (publ)
研究点 (1)
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