Study of Topical SOR007 Ointment for Cutaneous Metastases

Study Overview
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Brief Summary
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This study evaluates a topical nanoparticle paclitaxel ointment (SOR007) for the treatment of cutaneous metastases from non-melanoma cancer in adults. Three concentrations of SOR007 will be evaluated in dose-rising cohorts of three. An expanded cohort will treat additional subjects at the maximum tolerated dose.

Detailed Description
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This is a Phase 1/2, open-label, dose-rising study evaluating the safety, tolerability and preliminary efficacy of three concentrations of SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment (0.15%, 1.0%, and 2.0%) applied to non-melanoma cutaneous metastases. A treatment area of 50 cm2 will be selected by the Investigator. Using a gloved hand, subjects will apply one Finger Tip Unit (FTU) of SOR007 to the 50 cm2 treatment area twice daily at approximately the same time each day for 28 days, with the option of extending treatment an additional 28 days to total 56 days for subjects in the dose expansion phase. At each visit (Days 1, 8, 15, 29, and 43 for 28 treatment days; Days 8, 15, 29, 57, and 70 for 56 treatment days), at least two global and two close-up color photographs of the treatment area will be taken (with a ruler for scale). The photographs will be analyzed with ImageJ. Eligible lesions will be determined at baseline by the RECIST definition of measurable tumors (≥ 10mm in its longest diameter). The study will include a dose escalation phase and a dose expansion phase. In the dose escalation phase, formal safety reviews will be conducted after the last subject in each cohort of three subjects completes 15 days of treatment. The next dose level will enroll upon a finding of safety and tolerability. The top dose or the maximum tolerated dose (if DLT occurs) will be taken into the dose expansion phase and additional subjects will be enrolled to reach a maximum of 16 subjects at that dose.

Official Title
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Phase 1/2 Dose-Rising, Safety, Tolerability and Efficacy Study of Topical SOR007 for Cutaneous Metastases

Conditions
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Cutaneous Metastasis

Intervention / Treatment
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* Drug: SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Male and female patients ≥ 18 years of age; Malignancies resulting in cutaneous metastasis originating from: breast, lung, head and neck, pancreatic, urinary bladder, prostate, testicular, ovarian, uterine, cervical, gastric, adrenal, thyroid, parathyroid cancers, or other solid tumors; Cutaneous metastases diagnosis confirmed prior to consent by preferred institutional methodology which may include, but is not limited to: biopsy; conventional radiography; imaging techniques to include bone scan (scintigraphy), computed tomography (CT), fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT), magnetic resonance imaging (MRI), F-fluoromisonidazole-(F-FMISO) PET/CT, fluorothymidine-(FLT) PET/CT, fluoroestradiol-(FES) PET/CT, and PET/MRI; ECOG Grade 0 - 2, with minimum life expectancy of at least 3 months; At least one baseline eligible lesion. Per RECIST criteria (version 1.1), an eligible lesion at baseline is considered measurable when ≥ 10mm diameter in the longest diameter; Willing to refrain from using lotions, creams, etc. during the treatment period; Subjects with adequate organ and bone marrow function as defined below: ANC ≥ 1,500/µl Hemoglobin ≥ 9.5 grams/dL Platelets ≥ 75,000/µl AST (aspartate transaminase or SGOT)/ALT (alanine aminotransferase or SGPT) ≤ 3.0 x ULN and total bilirubin ≤ 2.0 x ULN with no evidence of cholestasis Creatinine ≤ 1.5x ULN; Last dose of any systemic non-taxane cytotoxic chemotherapy completed at least one day prior to Day 1. Last dose of any systemic taxane cytotoxic chemotherapy completed at least 4 weeks prior to Day 1 Willing to use appropriate birth control for patients of child-bearing potential; Abstinence from all manner of physical contact near the treatment area during and up to 2 weeks after the treatment phase. Exclusion Criteria: Open or ulcerated wound(s) extending through the dermis within the treatment area; Colorectal, hepatocellular, gallbladder, cholangiocarcinoma, neuroendocrine, melanomas, hematological and central nervous system (CNS) malignancies; Active viral hepatitis A, B, or C or preexisting or acute liver disease; Systemic treatment or localized treatment to target area with the following within the 4 weeks prior to the first treatment visit: radiotherapy, intralesional therapy; laser therapy surgery (other than biopsy), local hyperthermia, levulinic acid, 5-fluorouracil, high potency corticosteroids (including systemic steroids), retinoids, diclofenac, hyaluronic acid, imiquimod; Elective surgery for treatment of the cutaneous metastases during the study and up to 4 weeks after the treatment period. Cutaneous metastases are required to remain in-situ and measurable for up to 2 weeks after last treatment to achieve study objectives; Known allergic reactions, irritations or sensitivity to the active ingredients or other components of SOR007; Symptoms of a clinically significant illness that may place the subject at risk by trial participation or influence the outcome of the trial in the four weeks before first treatment and during the trial; Participation in the treatment phase of another clinical trial within the four weeks prior to treatment in this clinical trial; Investigator's opinion of subject's probable noncompliance or inability to understand the trial and/or give adequate informed consent; Evidence of current chronic alcohol or drug abuse; Pregnancy and/or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Phase 1/2, open-label, dose-rising trial of three concentrations of SOR007 (0.15%, 1.0%, 2.0%). During the dose escalation phase, the study will follow a standard 3+3 dose-ascending design. If a single dose limiting toxicity (DLT) is identified in one of three subjects in the cohort, a further three subjects will be enrolled at the same dose level. If one or more DLT occur in the three additional subjects enrolled in the cohort, dose escalation will stop and the prior dose level will be regarded as the Maximum Tolerated Dose (MTD) and taken forward into the dose expansion phase. If no further DLT are identified, dose escalation will continue, until either a DLT is identified at a higher dose or the top dose of 2% is reached. In the dose expansion phase, additional subjects will be enrolled up to a maximum of 12 subjects at the dose determined to be the MTD (or the top dose, 2.0% SOR007).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOR007 0.15%<br>0.15% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days | Drug: SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment<br>* One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.<br>|
| Experimental: SOR007 1.0%<br>1.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days | Drug: SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment<br>* One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.<br>|
| Experimental: SOR007 2.0%<br>2.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days or up to 56 days | Drug: SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment<br>* One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events | Treatment emergent adverse events will include all reported adverse events, laboratory assessments, physical examination findings, and vital signs. | Baseline through Day 59 (for 28 days of treatment) or Day 86 (for 56 days of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Clinical Response | Objective Clinical Response (Complete Clinical Response (CR) + Partial Response (PR)) is defined as the percentage of study subjects who achieve complete clinical response or partial response 14 days after last treatment (Day 43 or Day 70). Complete clinical response (CR) is defined as absence of any detectable residual disease in the treatment area; partial response (PR) as at least a 30% decrease in the sum of the diameters of eligible lesion(s) within the treatment area compared to baseline; progressive disease (PD) as at least a 20% increase in the sum of diameters of eligible lesion(s) within the treatment area, taking as reference the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); and stable disease (SD) as between that defined as PR or PD. Eligible lesions will be determined at baseline by the RECIST definition of measurable tumors (≥ 10mm in its longest diameter). | Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment) | 
| Change in Pain at the Treatment Area | Change in pain at the treatment area will be measured by the Numeric Rating Scale (NRS-11). The numerical scale ranges from 0 to 10, with 0 being no pain and 10 being the worst pain imaginable. A lower score equates to less severe pain (better outcome) and a higher score equates to more severe pain (worse outcome). | Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment) | 
| Objective Tumor Response (OTR) | Objective Tumor Response (OTR), defined as the difference in the lesion size within the treatment area between baseline and 14 days after the last dose in the dose group i.e. Day 43 for dose escalation Subjects, and dose expansion Group A Subjects; Day 70 for dose expansion Group B Subjects; or between baseline and last tumor assessment for early terminators. Four OTRs are calculated based on different definitions of lesion size: 1) Area of the primary eligible lesion, 2) Sum of area of all eligible lesions, 3) Longest diameter of the primary eligible lesion, and 4) Sum of longest diameter of all eligible lesions. | Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cutaneous metastases, cutaneous metastasis, skin metastases, skin metastasis