Cutaneous Metastasis
Conditions
Keywords
cutaneous metastases, cutaneous metastasis, skin metastases, skin metastasis
Brief summary
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
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.
Interventions
DRUGSOR007 (Uncoated Nanoparticle Paclitaxel) Ointment
One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.
Sponsors
US Biotest, Inc.
NanOlogy, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent; 2. Male and female patients ≥ 18 years of age; 3. 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; 4. 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; 5. ECOG Grade 0 - 2, with minimum life expectancy of at least 3 months; 6. 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; 7. Willing to refrain from using lotions, creams, etc. during the treatment period; 8. 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; 9. 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 10. Willing to use appropriate birth control for patients of child-bearing potential; 11. Abstinence from all manner of physical contact near the treatment area during and up to 2 weeks after the treatment phase.
Exclusion criteria
1. Open or ulcerated wound(s) extending through the dermis within the treatment area; 2. Colorectal, hepatocellular, gallbladder, cholangiocarcinoma, neuroendocrine, melanomas, hematological and central nervous system (CNS) malignancies; 3. Active viral hepatitis A, B, or C or preexisting or acute liver disease; 4. 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; 5. 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; 6. Known allergic reactions, irritations or sensitivity to the active ingredients or other components of SOR007; 7. 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; 8. Participation in the treatment phase of another clinical trial within the four weeks prior to treatment in this clinical trial; 9. Investigator's opinion of subject's probable noncompliance or inability to understand the trial and/or give adequate informed consent; 10. Evidence of current chronic alcohol or drug abuse; 11. Pregnancy and/or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events | Baseline through Day 59 (for 28 days of treatment) or Day 86 (for 56 days of treatment) | Treatment emergent adverse events will include all reported adverse events, laboratory assessments, physical examination findings, and vital signs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Clinical Response | Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment) | 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). |
| Change in Pain at the Treatment Area | Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment) | 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). |
| Objective Tumor Response (OTR) | Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SOR007 0.15% 0.15% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area. | 4 |
| SOR007 1.0% 1.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area. | 3 |
| SOR007 2.0% Group A 2.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area. | 5 |
| SOR007 2.0% Group B 2.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 56 days
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area. | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Decision to start another clinical trial. Not related to AE. | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 1 |
| Overall Study | Non-compliance with study schedule | 1 | 0 | 0 | 1 |
| Overall Study | Oncologist decision to start subject on IV chemotherapy prohibited under protocol. | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | SOR007 1.0% | SOR007 2.0% Group A | SOR007 2.0% Group B | SOR007 0.15% | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 8.3 | 63.2 years STANDARD_DEVIATION 11.3 | 63.0 years STANDARD_DEVIATION 10.8 | 62.8 years STANDARD_DEVIATION 12.7 | 63.4 years STANDARD_DEVIATION 10.3 |
| Body Mass Index | 26.13 kg/m^2 STANDARD_DEVIATION 3.96 | 29.54 kg/m^2 STANDARD_DEVIATION 4.94 | 25.05 kg/m^2 STANDARD_DEVIATION 5.21 | 23.23 kg/m^2 STANDARD_DEVIATION 4.51 | 25.85 kg/m^2 STANDARD_DEVIATION 5.07 |
| ECOG Performance Status | 0.7 units on a scale STANDARD_DEVIATION 0.6 | 0.6 units on a scale STANDARD_DEVIATION 0.9 | 0.7 units on a scale STANDARD_DEVIATION 0.5 | 1.0 units on a scale STANDARD_DEVIATION 0.8 | 0.7 units on a scale STANDARD_DEVIATION 0.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 9 Participants | 3 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 6 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 10 Participants | 4 Participants | 21 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 0 / 3 | 0 / 5 | 0 / 11 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 5 / 5 | 10 / 11 |
| serious Total, serious adverse events | 1 / 4 | 0 / 3 | 2 / 5 | 4 / 11 |
Outcome results
Primary
Incidence of Treatment Emergent Adverse Events
Treatment emergent adverse events will include all reported adverse events, laboratory assessments, physical examination findings, and vital signs.
Time frame: Baseline through Day 59 (for 28 days of treatment) or Day 86 (for 56 days of treatment)
Population: All subjects who received SOR007 were included in the analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SOR007 0.15% | Incidence of Treatment Emergent Adverse Events | 4 Participants |
| SOR007 1.0% | Incidence of Treatment Emergent Adverse Events | 3 Participants |
| SOR007 2.0% Group A | Incidence of Treatment Emergent Adverse Events | 5 Participants |
| SOR007 2.0% Group B | Incidence of Treatment Emergent Adverse Events | 10 Participants |
Secondary
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).
Time frame: Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment)
Population: All subjects who received SOR007 were included in the analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOR007 0.15% | Change in Pain at the Treatment Area | Baseline (Day 1) | 0.0 units on a scale | Standard Deviation 0 |
| SOR007 0.15% | Change in Pain at the Treatment Area | 2 Weeks after Last Dose (Day 43 for 28-day treatment groups or Day 70 for 56-day treatment groups) | 0.0 units on a scale | Standard Deviation 0 |
| SOR007 1.0% | Change in Pain at the Treatment Area | 2 Weeks after Last Dose (Day 43 for 28-day treatment groups or Day 70 for 56-day treatment groups) | 1.0 units on a scale | Standard Deviation 1.7 |
| SOR007 1.0% | Change in Pain at the Treatment Area | Baseline (Day 1) | 0.3 units on a scale | Standard Deviation 0.6 |
| SOR007 2.0% Group A | Change in Pain at the Treatment Area | Baseline (Day 1) | 1.4 units on a scale | Standard Deviation 1.3 |
| SOR007 2.0% Group A | Change in Pain at the Treatment Area | 2 Weeks after Last Dose (Day 43 for 28-day treatment groups or Day 70 for 56-day treatment groups) | 3.8 units on a scale | Standard Deviation 2.6 |
| SOR007 2.0% Group B | Change in Pain at the Treatment Area | Baseline (Day 1) | 1.1 units on a scale | Standard Deviation 2 |
| SOR007 2.0% Group B | Change in Pain at the Treatment Area | 2 Weeks after Last Dose (Day 43 for 28-day treatment groups or Day 70 for 56-day treatment groups) | 0.3 units on a scale | Standard Deviation 0.7 |
Secondary
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).
Time frame: Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment)
Population: Of the 23 Subjects enrolled, evaluable photography 14 days after the last dose of SOR007 was provided in 14 (60.9%) Subjects; two in the 0.15% treatment group, three in the 1.0% treatment group, four in 2.0% A treatment group, and five in 2.0% B treatment group.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SOR007 0.15% | Objective Clinical Response | Partial Response | 0 Participants |
| SOR007 0.15% | Objective Clinical Response | Complete Response | 0 Participants |
| SOR007 0.15% | Objective Clinical Response | Progressive Disease | 1 Participants |
| SOR007 0.15% | Objective Clinical Response | Stable Disease | 1 Participants |
| SOR007 1.0% | Objective Clinical Response | Partial Response | 2 Participants |
| SOR007 1.0% | Objective Clinical Response | Progressive Disease | 0 Participants |
| SOR007 1.0% | Objective Clinical Response | Complete Response | 0 Participants |
| SOR007 1.0% | Objective Clinical Response | Stable Disease | 1 Participants |
| SOR007 2.0% Group A | Objective Clinical Response | Complete Response | 0 Participants |
| SOR007 2.0% Group A | Objective Clinical Response | Partial Response | 0 Participants |
| SOR007 2.0% Group A | Objective Clinical Response | Stable Disease | 1 Participants |
| SOR007 2.0% Group A | Objective Clinical Response | Progressive Disease | 3 Participants |
| SOR007 2.0% Group B | Objective Clinical Response | Stable Disease | 4 Participants |
| SOR007 2.0% Group B | Objective Clinical Response | Progressive Disease | 0 Participants |
| SOR007 2.0% Group B | Objective Clinical Response | Partial Response | 0 Participants |
| SOR007 2.0% Group B | Objective Clinical Response | Complete Response | 1 Participants |
Secondary
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.
Time frame: Baseline and Day 43 (for 28 days of treatment) or Day 70 (for 56 days of treatment)
Population: One subject in SOR007 2.0% Group A was not included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOR007 0.15% | Objective Tumor Response (OTR) | Based on Area of the Primary Eligible Lesion | -31.03 mm^2 | Standard Deviation 22 |
| SOR007 0.15% | Objective Tumor Response (OTR) | Based on Total Area of all Eligible Lesions | -40.57 mm^2 | Standard Deviation 25.56 |
| SOR007 0.15% | Objective Tumor Response (OTR) | Based on Longest Diameter of the Primary Eligible Lesion | -5.50 mm^2 | Standard Deviation 9.75 |
| SOR007 0.15% | Objective Tumor Response (OTR) | Based on Total Longest Diameter of all Eligible Lesions | -5.75 mm^2 | Standard Deviation 9.58 |
| SOR007 1.0% | Objective Tumor Response (OTR) | Based on Total Longest Diameter of all Eligible Lesions | 4.88 mm^2 | Standard Deviation 6.17 |
| SOR007 1.0% | Objective Tumor Response (OTR) | Based on Area of the Primary Eligible Lesion | 302.63 mm^2 | Standard Deviation 330.55 |
| SOR007 1.0% | Objective Tumor Response (OTR) | Based on Longest Diameter of the Primary Eligible Lesion | 5.11 mm^2 | Standard Deviation 6.55 |
| SOR007 1.0% | Objective Tumor Response (OTR) | Based on Total Area of all Eligible Lesions | 407.33 mm^2 | Standard Deviation 499.66 |
| SOR007 2.0% Group A | Objective Tumor Response (OTR) | Based on Total Longest Diameter of all Eligible Lesions | 1.26 mm^2 | Standard Deviation 37.34 |
| SOR007 2.0% Group A | Objective Tumor Response (OTR) | Based on Total Area of all Eligible Lesions | -176.61 mm^2 | Standard Deviation 883.76 |
| SOR007 2.0% Group A | Objective Tumor Response (OTR) | Based on Longest Diameter of the Primary Eligible Lesion | -0.96 mm^2 | Standard Deviation 16.57 |
| SOR007 2.0% Group A | Objective Tumor Response (OTR) | Based on Area of the Primary Eligible Lesion | -165.05 mm^2 | Standard Deviation 679.24 |