A Phase II Study to Evaluate the Safety and Efficacy of OQL011 on VEGFR inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 112
- 试验地点
- 2
- 主要终点
- Part 2:
研究概览
简要总结
Primary objective:
Part2: To evaluate the efficacy of OQL011 doses I-III compared to vehicle for thetreatment of HFSR as measured by the proportion of patients achieving IGA-HFSRgrade 0 or 1 at Week 2.
Secondary objective:
Part2: To evaluate the efficacy of OQL011 doses I-III compared to vehicle for thetreatment of HFSR as measured by the proportion of patients achieving IGA-HFSRgrade 0 or 1 at Week 4.
Toevaluate the efficacy of OQL011 doses I-III compared to vehicle for the treatmentof HFSR as measured by the proportion of patients achieving at least 2 gradeimprovement in IGA-HFSR at Weeks 2 and 4.
Toevaluate the efficacy of OQL011 doses I-III versus vehicle measured by, NCICTCAE v5.0 for PPE, HF-QoL, and daily pain score (Numerical Pain Rating Scale(NPRS)) at Week 2 and Week 4.
Tocompare the efficacy of OQL011 among doses I, II, and III, as well as toevaluate by dose level the exposure-response relationship of OQL011.
Toevaluate the safety of OQL011 doses I-III versus vehicle in patients with HFSR.
Toevaluate PK of OQL011 doses I-III in patients with HFSR.
Toevaluate compliance in using VEGFRi between OQL011 doses I-III, or vehiclecontrol per patient diary.
Exploratory objective:
Part2: To evaluate compliance in using OQL011 dose I-III, or vehicle control perpatient diary.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •The subjects will be included in the study based on the following criteria: 1) Patient must be age greater than or equal to 18 years.
- •Patient must have a confirmed cancer diagnosis for which VEGFRi treatment is indicated, and must be currently under VEGFRi-based anticancer therapy with stable dosage for greater than or equal to 1 week.
- •This treatment may be VEGFRi monotherapy or VEGFRi-based combination therapy, so long as it does not include prohibited therapies.
- •Patient must have shown signs of HFSR that meet the NCI CTCAE v5.0 Term Palmar-plantar Erythrodysesthesia Syndrome criteria as grade 2 or higher.
- •Patient is able to use topical medications and complete questionnaires reliably.
- •ECOG performance score less than or equal to 2 7) Patient must have the ability to understand and the willingness to sign a written informed consent prior to study entry.
排除标准
- •The subjects will be excluded from the study based on the following criteria: 1) Patient with unresolved hand or foot skin disorders (CTCAE grade 2 or higher) due to other medications within 4 weeks prior to study entry.
- •Patient who is using other topical medications in the hands or feet area and cannot stop such usage greater than7 days ahead of randomization.
- •Patient who is on concurrent cancer medications that can cause skin reactions in hands or feet, such as capecitabine, pegylated liposomal doxorubicin, 5-fluorouracil, dabrafenib, vemurafenib, doxorubicin, docetaxel, cytarabine, ramucirumab and bevacizumab.
- •Patient who is under uncontrolled intercurrent illness including, but not limited to, inadequately controlled nausea, vomiting, diarrhea or other conditions which may contribute to hypovolemia, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, recent myocardial infarction, uncontrolled hypotension (including orthostatic hypotension) or hypertension, cardiac arrhythmia, or psychiatric illness and social situations that would limit compliance with study requirements.
- •Patient who has contraindication with the active compound, including severe anemia, increased intracranial pressure, known hypersensitivity.
- •Patient who has other skin disorders that will affect the efficacy evaluation on hands and feet area, including but not limited to, tinea of feet and hands, handperfoot eczema, palmoplantar pustulosis, palmoplantar keratosis, acrodermatitis continua etc.
- •Patient who used of phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil, vardenafil, and tadalafil within past 7 days.
- •Patient with significantly abnormal lab test: Inadequate hematologic function as indicated by: • Absolute neutrophil counts (ANC) less than or equal to1,000 per mm3 • Hemoglobin (Hgb) less than or equal to8.0 g per dL • Platelet count less than or equal to75, 000 per mm3 • PT or PTT greater than 1.5 x ULN (if patients on anticoagulants: PT INR greater than3.5 x ULN).
- •Inadequate renal and liver function as indicated by: • Albumin less than 2.8g per dL • Total bilirubin greater than or equal to 1.5 x ULN (or greater than or equal to2.5 x ULN for patients with Gilbert’s syndrome) • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase greater than or equal to3 x ULN (or greater than or equal to5 x ULN for patients with liver cancer) • Creatinine greater than 2.0 x ULN 9) Pregnant or nursing women.
- •Women of childbearing potential who are unwilling to comply with contraceptive requirements.
- •Highly effective contraception which include two forms of birth control method (i.e., a hormonal method plus a barrier method) is advised for at least 2 weeks prior to study treatment and during study participation.
结局指标
主要结局
Part 2:
时间窗: Nine patients will go through a PK study. Blood samples will be taken on Day 0 at pre-dose and 5 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hour, 2 hour, 4 hour, 6 hour, 8 hour, after the first application of investigational drugs.
Part 1:
时间窗: Nine patients will go through a PK study. Blood samples will be taken on Day 0 at pre-dose and 5 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hour, 2 hour, 4 hour, 6 hour, 8 hour, after the first application of investigational drugs.
To evaluate the efficacy of OQL011 dose I versus vehicle measured by the proportion of patients achieving NCI CTCAE v5.0 for PPE grade 0 or 1 by Week 3.
时间窗: Nine patients will go through a PK study. Blood samples will be taken on Day 0 at pre-dose and 5 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hour, 2 hour, 4 hour, 6 hour, 8 hour, after the first application of investigational drugs.
To evaluate the efficacy of OQL011 dose II and dose III compared to vehicle for the treatment of HFSR as measured by the proportion of patients achieving NCI CTCAE v5.0 for PPE grade 0 or 1 by Week 3.
时间窗: Nine patients will go through a PK study. Blood samples will be taken on Day 0 at pre-dose and 5 min, 15 min, 30 min, 45 min, 1 hour, 1.5 hour, 2 hour, 4 hour, 6 hour, 8 hour, after the first application of investigational drugs.
次要结局
- To evaluate the efficacy of OQL011 dose II and dose III versus vehicle measured by IGA-i, IGA-c, NCI CTCAE v5.0 for PPE, HF-QoL, daily pain score (VAS) by Week 3 and Week 6.(To evaluate the safety of OQL011 dose II and dose III versus vehicle in patients with HFSR.)