A Study to Investigate OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients

Hand-Foot Skin Reaction (HFSR) Clinical Trial

— NOVA-II  

Official title:

A Phase II Study to Evaluate the Safety and Efficacy of OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04088318
• Other study ID #: OQL011B002
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 9, 2019
• Est. completion date: June 2024

Study information

• Verified date: September 2023
• Source: OnQuality Pharmaceuticals (USA) LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 170
• Est. completion date: June 2024
• Est. primary completion date: February 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• Patient who is using other topical medications in the hands or feet area and cannot stop such usage >7 days ahead of randomization.

• 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).

• 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.

• 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, hand/foot eczema, palmoplantar pustulosis, palmoplantar keratosis, acrodermatitis continua etc.

• Patient who used 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) = 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)

• 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.

• 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.

Related Conditions & MeSH terms

• Hand-Foot Skin Reaction (HFSR)

Intervention

Drug:
• OQL011
OQL011 is an ointment containing active ingredient.
• Vehicle Ointment
Vehicle ointment is an ointment containing no active ingredient.

Locations

Country	Name	City	State
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai
China	Shanghai Sixth People's Hospital	Shanghai	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai	Shanghai
China	Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Taizhou People's Hospital	Taizhou	Jiangsu
China	Affiliated Hospital of Jiangnan University	Wuxi	Jiangsu
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
India	Oncoville Cancer Hospital and Research Center	Bangalore	Karnataka
India	S.P Medical College & AG Hospitals, Bikaner	Bikaner	Dimhans
India	Aadhar Health Institute	Hisar	Haryana
India	Noble Hospital, Pune	Hisar	Haryana
India	Mumbai Oncocare Centre	Mumbai	Maharashtra
India	HCG Manavata Cancer centre, Nashik	Naka	Nashik
India	Kiran Multi Super Speciality Hospital & Research Center	Surat	Gujarat
India	Kailash Cancer Hospital and Research Center	Vadodara	Gujarat
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Einstein Center for Cancer Care	Bronx	New York
United States	Gabrail Cancer Centre	Canton	Ohio
United States	Northwestern University - Hospital	Chicago	Illinois
United States	Ohio State University Dermatology	Columbus	Ohio
United States	Western Regional Medical Center	Goodyear	Arizona
United States	Innovative Clinical Research Institute	Henderson	Nevada
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Louisville - Hospital	Louisville	Kentucky
United States	AP Medical Research	Miami	Florida
United States	Yale University - Hospital	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
OnQuality Pharmaceuticals (USA) LLC

Countries where clinical trial is conducted

United States,  China,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	(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	(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	The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.	3 weeks and 6 weeks
Secondary	(For Part 2) Proportion of patients achieving IGA-HFSR grade 0 or 1	The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.	4 weeks
Secondary	(For Part 2) Proportion of patients achieving at least two-grade improvement in IGA-HFSR	The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.	2 weeks and 4 weeks
Secondary	(For Part 1) Proportion of patients who achieve NCI CTCAE v5.0 - PPE grade 0 or 1		6 weeks
Secondary	(For Part 2) Change from baseline in NCI CTCAE v5.0 - PPE grade		2 weeks and 4 weeks
Secondary	Change from baseline in HF-QoL (Hand-Foot Skin Reaction and Quality of Life) Questionnaire total score	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)	3 weeks and 6 weeks (Part 1) OR 2 weeks and 4 weeks (Part 2)
Secondary	(For Part 1) Change from baseline in patient reported pain using VAS (Visual Analog Scale)	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.	3 weeks and 6 weeks
Secondary	(For Part 2) Change from baseline in patient reported pain using NPRS (Numerical Pain Rating Scale)	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.	2 weeks and 4 weeks
Secondary	(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	The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.	3 weeks and 6 weeks
Secondary	Safety assessment by type, incidence and intensity of adverse events		6 weeks (Part 1) and 4 weeks (Part 2)
Secondary	Plasma concentration of active compound and its derivatives		1 day
Secondary	(For Part 2) The exposure-response relationship of different dose level OQL011		4 weeks