A Study to Investigate OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients
- Conditions
- Hand-Foot Skin Reaction (HFSR)
- Interventions
- Drug: Vehicle Ointment
- Registration Number
- NCT04088318
- Lead Sponsor
- OnQuality Pharmaceuticals (USA) LLC
- Brief Summary
Hand-Foot Skin Reaction (HFSR) is a common adverse event induced by Vascular Endothelial Growth Receptor Inhibitor (VEGFRi) treatment in cancer patients. The main purpose of this study is to evaluate the safety and efficacy of OQL011 compared to vehicle ointment in treating patients with moderate to severe VEGFRi-associated HFSR. This study will also identify an optimal dosage for Phase III study and explore the pharmacokinetics profile of OQL011 in HFSR patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 170
- Patient must be age ≥ 18 years.
- Patient must have a confirmed cancer diagnosis for which VEGFRi treatment is indicated, and must be currently under VEGFRi-based anti-cancer therapy with stable dosage for ≥ 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 (for Part 1) the NCI CTCAE v5.0 - PPE grade 2 or higher OR (for Part 2) IGA-HFSR criteria of grade 3 or higher.
- Patient on pain medications is allowed provided they have been on stable dosage in the past 1 week and is going to continue at the same dosage.
- Patient is able to use topical medications and complete questionnaires reliably.
- Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
- Patient must have the ability to understand and the willingness to sign a written informed consent prior to study entry.
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Patient with unresolved hand or foot skin disorders (NCI CTCAE v5.0 grade 2 or higher) due to other medications within 4 weeks prior to study entry.
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Patient who is using other topical medications in the hands or feet area and cannot stop such usage >7 days ahead of randomization.
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Patient who is using other concurrent cancer medications, such as capecitabine, pegylated liposomal doxorubicin, 5-fluorouracil, dabrafenib, vemurafenib, doxorubicin, docetaxel, cytarabine, ramucirumab and bevacizumab, which may result in hand-foot syndrome (HFS).
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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 or hypertension, cardiac arrhythmia, or psychiatric illness and social situations that would limit compliance with study requirements.
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Patient who has contraindication with the active compound, including severe anemia, increased intracranial pressure, known hypersensitivity.
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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, hand/foot eczema, palmoplantar pustulosis, palmoplantar keratosis, acrodermatitis continua etc.
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Patient who used phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil, vardenafil, and tadalafil within past 7 days.
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Patient with significantly abnormal lab test:
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Inadequate hematologic function as indicated by:
- Absolute neutrophil counts (ANC) ≤ 1,000 /mm^3
- Hemoglobin (Hgb) ≤ 8.0 g/dL
- Platelet count ≤ 75,000 /mm^3
- PT or PTT > 1.5 x ULN (if patients on anticoagulants: PT INR > 3.5 x ULN)
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Inadequate renal and liver function as indicated by:
- Albumin < 2.8 g/dL
- Total bilirubin ≥ 1.5 x ULN (or ≥ 2.5 x ULN for patients with Gilbert's syndrome)
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≥ 3 x ULN (or ≥ 5 x ULN for patients with liver cancer)
- Creatinine > 2.0 x ULN.
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Pregnant or nursing women.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vehicle Ointment Vehicle Ointment Vehicle ointment, to be applied topically, three times a day, for up to six weeks (in Part 1) or four weeks (in Part 2) OQL011 Dose III OQL011 OQL011, Dose III, ointment, to be applied topically, three times a day, for up to six weeks (in Part 1) or four weeks (in Part 2) OQL011 Dose II OQL011 OQL011, Dose II, ointment, to be applied topically, three times a day, for up to six weeks (in Part 1) or four weeks (in Part 2) OQL011 Dose I OQL011 OQL011, Dose I, ointment, to be applied topically, three times a day, for up to six weeks (in Part 1) or four weeks (in Part 2)
- Primary Outcome Measures
Name Time Method (For Part 1) Proportion of patients who achieve NCI CTCAE v5.0 - Palmar-Plantar Erythrodysesthesia (PPE) grade 0 or 1 OR (for Part 2) The proportion of patients achieving IGA-HFSR grade 0 or 1 3 weeks (Part 1) OR 2 weeks (Part 2)
- Secondary Outcome Measures
Name Time Method (For Part 1) Proportion of patients who achieve NCI CTCAE v5.0 - PPE grade 0 or 1 6 weeks (For Part 2) Change from baseline in NCI CTCAE v5.0 - PPE grade 2 weeks and 4 weeks (For Part 2) The exposure-response relationship of different dose level OQL011 4 weeks Change from baseline in HF-QoL (Hand-Foot Skin Reaction and Quality of Life) Questionnaire total score 3 weeks and 6 weeks (Part 1) OR 2 weeks and 4 weeks (Part 2) HF-QoL questionnaire is comprised of a 20-item symptom domain and an 18-item daily activity domain. Each item is rated on a 5-point scale from 0 (not at all) to 4 (always or extremely) during the previous week. The HF-QoL symptom and daily activity total scores are transformed to a scale of 0 to 100, based on the sum of each unit-weighted item score divided by the maximum score. Higher scores on the HF-QoL indicate worse quality of life or greater symptom burden. (refer to R. T. Anderson et al., The Oncologist 2015;20:831-838)
Safety assessment by type, incidence and intensity of adverse events 6 weeks (Part 1) and 4 weeks (Part 2) (For Part 1) Change from baseline in patient reported pain using VAS (Visual Analog Scale) 3 weeks and 6 weeks The subject records pain associated with HFSR using 100 mm VAS ranging from "no pain" at 0 mm to "unbearable pain" at 100 mm on the paper VAS.
(For Part 1) Proportion of patients who have improvement in HFSR severity and achieve clear (0) or almost clear (1) as measured by IGA-c (Centrally-assessed Investigator's Global Assessment) scale 3 weeks and 6 weeks The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.
(For Part 2) Change from baseline in patient reported pain using NPRS (Numerical Pain Rating Scale) 2 weeks and 4 weeks The subject records pain associated with HFSR using score 0 to 10 ranging from "no pain" for Score 0 to "unbearable pain" for Score 10.
Plasma concentration of active compound and its derivatives 1 day (For Part 1) Proportion of patients who have improvement in HFSR severity and achieve clear (0) or almost clear (1) as measured by IGA-i (Investigator-assessed Investigator's Global Assessment) scale 3 weeks and 6 weeks The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.
(For Part 2) Proportion of patients achieving IGA-HFSR grade 0 or 1 4 weeks The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.
(For Part 2) Proportion of patients achieving at least two-grade improvement in IGA-HFSR 2 weeks and 4 weeks The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.
Trial Locations
- Locations (32)
Gabrail Cancer Centre
🇺🇸Canton, Ohio, United States
Mumbai Oncocare Centre
🇮🇳Mumbai, Maharashtra, India
Noble Hospital, Pune
🇮🇳Hisar, Haryana, India
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Northwestern University - Hospital
🇺🇸Chicago, Illinois, United States
Innovative Clinical Research Institute
🇺🇸Henderson, Nevada, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Yale University - Hospital
🇺🇸New Haven, Connecticut, United States
University of Louisville - Hospital
🇺🇸Louisville, Kentucky, United States
AP Medical Research
🇺🇸Miami, Florida, United States
Taizhou People's Hospital
🇨🇳Taizhou, Jiangsu, China
Huashan Hospital Affiliated to Fudan University
🇨🇳Shanghai, Shanghai, China
Montefiore Einstein Center for Cancer Care
🇺🇸Bronx, New York, United States
Ohio State University Dermatology
🇺🇸Columbus, Ohio, United States
HCG Manavata Cancer centre, Nashik
🇮🇳Naka, Nashik, India
Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Affiliated Hospital of Jiangnan University
🇨🇳Wuxi, Jiangsu, China
Shanghai Tenth People's Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Sixth People's Hospital
🇨🇳Shanghai, Shanghai, China
Kiran Multi Super Speciality Hospital & Research Center
🇮🇳Sūrat, Gujarat, India
Kailash Cancer Hospital and Research Center
🇮🇳Vadodara, Gujarat, India
Aadhar Health Institute
🇮🇳Hisar, Haryana, India
Oncoville Cancer Hospital and Research Center
🇮🇳Bangalore, Karnataka, India
Nantong Tumor Hospital
🇨🇳Nantong, Jiangsu, China
S.P Medical College & AG Hospitals, Bikaner
🇮🇳Bīkaner, Dimhans, India
Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, Zhejiang, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
Western Regional Medical Center
🇺🇸Goodyear, Arizona, United States