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

• ClinicalTrials.gov Identifier: NCT04088318
• Recruitment Status: Recruiting
• First Posted: September 12, 2019
• Last Update Posted: January 18, 2023
• Sponsor: OnQuality Pharmaceuticals (USA) LLC
• Information provided by (Responsible Party): OnQuality Pharmaceuticals (USA) LLC

Tracking Information

• First Submitted Date: August 30, 2019
• First Posted Date: September 12, 2019
• Last Update Posted Date: January 18, 2023
• Actual Study Start Date: December 9, 2019
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 13, 2022): (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 [ Time Frame: 3 weeks (Part 1) OR 2 weeks (Part 2) ]
• Original Primary Outcome Measures (submitted: September 11, 2019): Proportion of patients who achieve NCI CTCAE v5.0 - Palmar-Plantar Erythrodysesthesia (PPE) grade 0 or 1 [ Time Frame: 3 weeks ]

Current Secondary Outcome Measures (submitted: July 13, 2022)

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

Original Secondary Outcome Measures (submitted: September 11, 2019)

• 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 [ Time Frame: 3 weeks and 6 weeks ]
  The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.
• Proportion of patients who achieve NCI CTCAE v5.0 - PPE grade 0 or 1 [ Time Frame: 6 weeks ]
• Change from baseline in HF-QoL (Hand-Foot Skin Reaction and Quality of Life) Questionnaire total score [ Time Frame: 3 weeks and 6 weeks ]
  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)
• Change from baseline in patient reported pain using VAS (Visual Analog Scale) [ Time Frame: 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.
• 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 [ Time Frame: 3 weeks and 6 weeks ]
  The IGA scale ranges from grade 0 (clear) to 4 (severe), the higher the score, the worse the condition.
• Safety assessment by type, incidence and intensity of adverse events [ Time Frame: 6 weeks ]
• Plasma concentration of active compound and its derivatives [ Time Frame: 1 day ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Supportive Care
• Condition: Hand-Foot Skin Reaction (HFSR)

Intervention

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

Study Arms

• Experimental: OQL011 Dose I
  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)
  Intervention: Drug: OQL011
• Experimental: OQL011 Dose II
  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)
  Intervention: Drug: OQL011
• Experimental: OQL011 Dose III
  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)
  Intervention: Drug: OQL011
• 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)
  Intervention: Drug: Vehicle Ointment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 13, 2022): 170
• Original Estimated Enrollment (submitted: September 11, 2019): 112
• Estimated Study Completion Date: October 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mark Webb, PhD; +1-801-618-8292; Mark.Webb@OnQualityRx.com

Contact: Johnny Ju, MSc; +86-137-6163-6367; Juegang.Ju@OnQualityRx.com

• Listed Location Countries: China, India, United States

Administrative Information

• NCT Number: NCT04088318
• Other Study ID Numbers: OQL011B002
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: There is no plan to make individual participant data (IPD) available to other researchers.

• Current Responsible Party: OnQuality Pharmaceuticals (USA) LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: OnQuality Pharmaceuticals (USA) LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mario E. Lacouture, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: OnQuality Pharmaceuticals (USA) LLC
• Verification Date: January 2023