Clinical trial NCT04088318: A Study to Investigate OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hand-Foot Skin Reaction (HFSR)
Lead sponsor: OnQuality Pharmaceuticals (USA) LLC
Sponsor class: INDUSTRY
First posted: 2019-09-12
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: (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
timeFrame: 3 weeks (Part 1) OR 2 weeks (Part 2)
Secondary outcomes:
measure: (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
timeFrame: 3 weeks and 6 weeks
measure: (For Part 2) Proportion of patients achieving IGA-HFSR grade 0 or 1
timeFrame: 4 weeks
measure: (For Part 2) Proportion of patients achieving at least two-grade improvement in IGA-HFSR
timeFrame: 2 weeks and 4 weeks
measure: (For Part 1) Proportion of patients who achieve NCI CTCAE v5.0 - PPE grade 0 or 1
timeFrame: 6 weeks
measure: (For Part 2) Change from baseline in NCI CTCAE v5.0 - PPE grade
timeFrame: 2 weeks and 4 weeks
measure: Change from baseline in HF-QoL (Hand-Foot Skin Reaction and Quality of Life) Questionnaire total score
timeFrame: 3 weeks and 6 weeks (Part 1) OR 2 weeks and 4 weeks (Part 2)
measure: (For Part 1) Change from baseline in patient reported pain using VAS (Visual Analog Scale)
timeFrame: 3 weeks and 6 weeks
measure: (For Part 2) Change from baseline in patient reported pain using NPRS (Numerical Pain Rating Scale)
timeFrame: 2 weeks and 4 weeks
measure: (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
timeFrame: 3 weeks and 6 weeks
measure: Safety assessment by type, incidence and intensity of adverse events
timeFrame: 6 weeks (Part 1) and 4 weeks (Part 2)
measure: Plasma concentration of active compound and its derivatives
timeFrame: 1 day
measure: (For Part 2) The exposure-response relationship of different dose level OQL011
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Western Regional Medical Center
state: Arizona
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale University - Hospital
state: Connecticut
city: Miami
country: United States
facility: AP Medical Research
state: Florida
city: Chicago
country: United States
facility: Northwestern University - Hospital
state: Illinois
city: Louisville
country: United States
facility: University of Louisville - Hospital
state: Kentucky
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Henderson
country: United States
facility: Innovative Clinical Research Institute
state: Nevada
city: Bronx
country: United States
facility: Montefiore Einstein Center for Cancer Care
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Centre
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Dermatology
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Taizhou
country: China
facility: Taizhou People's Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Bīkaner
country: India
facility: S.P Medical College & AG Hospitals, Bikaner
state: Dimhans
city: Sūrat
country: India
facility: Kiran Multi Super Speciality Hospital & Research Center
state: Gujarat
city: Vadodara
country: India
facility: Kailash Cancer Hospital and Research Center
state: Gujarat
city: Hisar
country: India
facility: Aadhar Health Institute
state: Haryana
city: Hisar
country: India
facility: Noble Hospital, Pune
state: Haryana
city: Bangalore
country: India
facility: Oncoville Cancer Hospital and Research Center
state: Karnataka
city: Mumbai
country: India
facility: Mumbai Oncocare Centre
state: Maharashtra
city: Naka
country: India
facility: HCG Manavata Cancer centre, Nashik
state: Nashik
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Mario E. Lacouture, MD
role: PRINCIPAL_INVESTIGATOR
References: