Study of SOR007 Ointment for Cervical Intraepithelial Neoplasia (CIN)

Cervical Intraepithelial Neoplasia Clinical Trial

Official title:

Phase 2a Dose-Rising, Safety, Tolerability, and Efficacy Study of Topical SOR007 for Cervical Intraepithelial Neoplasia (CIN)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03143491
• Other study ID #: SOR007-2017-02
• Status: Withdrawn
• Phase: Phase 2
• First received: May 4, 2017
• Last updated: October 16, 2017
• Start date: October 1, 2017
• Est. completion date: March 1, 2019

Study information

• Verified date: October 2017
• Source: DFB Soria, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2, open-label, dose-rising study evaluating the safety, tolerability, and preliminary efficacy of three concentrations of SOR007 ointment (0.15%, 1.0%, and 2.0%) applied topically once per week for four weeks to the ectocervix of subjects with high grade cervical intraepithelial neoplasia (CIN).

Description:

In this Phase 2, open-label, dose-rising study, subjects with high grade (CIN 2 or 3) CIN will receive once-weekly topical application of SOR007 ointment to the ectocervix for four weeks. Subjects will be enrolled in three dose-escalating cohorts of three subjects assigned consecutively to receive 0.15%, 1.0%, or 2.0% SOR007 ointment. At the final study visit (Visit 7) subjects will undergo an excision or punch biopsy to record the stage of CIN. PK samples will be obtained post-application on Day 0 at 1, 2, 4, 6, and 24 hours' post-application on Day 1. Additional PK samples will be collected at each visit. Plasma samples for PK analysis on Days 7, 14 and 21 will be collected prior to SOR007 application.

The Medical Monitor will review all available data prior to dose escalation. Dose-escalation of SOR007 will be determined by the Medical Monitor. This will be repeated for each escalated dose until all dose levels have been enrolled or a dose is determined unsafe. Safety will be assessed in an ongoing manner and formal safety reviews will be conducted twice for each cohort: after Day 14 and after Day 49 of the last subject in the cohort. If a safety or tolerability issue becomes apparent in a cohort, an additional three subjects will be enrolled at that dose level, for a maximum of six subjects in that cohort. If ≥ 1 safety or tolerability issue occurs in the additional 3 subjects, the prior dose-level will be determined to be the highest dose with an acceptable safety and tolerability profile. If no further safety and tolerability issues are identified in the expanded cohort, dose-escalation will continue.

Once the highest dose with an acceptable safety and tolerability profile has been determined by the Medical Monitor, PI, and Sponsor Medical Director, a further 3 subjects will be enrolled to that dose level in order to increase the subject numbers.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 1, 2019
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent;

• Female adults = 18 years of age;

• Presence of newly diagnosed (within 8 weeks prior to administration of SOR007), histologically confirmed CIN 2, CIN 2/3 or CIN 3;

• Candidate for observation, treatment, or removal of CIN;

• Satisfactory colposcopy (visualization of the entire squamocolumnar junction and margins of any visible lesions);

• Appropriate contraception throughout study period;

Exclusion Criteria:

• Pap smear and/or colposcopy suspicious for invasive disease;

• History of previous conization/LEEP;

• History of toxic shock syndrome;

• Known allergy or prior intolerance to paclitaxel;

• Immunodeficiency (including HIV/AIDS and immunosuppressive medication);

• Current, reported participation in another experimental, interventional protocol;

• Active lower genital infection(s);

• Malignant disease at the time of inclusion, with the exclusion of basal cell carcinoma (BCC) or dermal carcinoma-in-situ;

• Concurrent treatment with cytotoxic, radiation, immune-stimulative, or immune-suppressive therapy, or with systemic corticosteroid dose of > 5 mg/d or prednisone (or its equivalent);

• Concomitant use of topical vaginal medications or products;

• Pregnant or lactating;

• Pregnancy planned within six (6) months following study drug application;

• Significant acute or chronic medical or psychiatric illness or other environmental or social factors that, in the opinion of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Intraepithelial Neoplasia
• Neoplasms

Intervention

Drug:
• SOR007 (Uncoated Nanoparticulate Paclitaxel) Ointment
1 mL of SOR007 applied topically to the ectocervix once-weekly for four weeks.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
DFB Soria, LLC	US Biotest, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	49 days
Secondary	Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) of SOR007	Plasma samples for pharmacokinetic (PK) analysis will be obtained on Day 0 at 1, 2, 4, and 6 hours post-application, at 24 hours' post-application (Day 1), and at each subsequent clinic visit (samples on Days 7, 14, and 21 will be obtained prior to dose application).	49 days
Secondary	Pharmacokinetics: Peak plasma concentration (Cmax) of SOR007	Plasma samples for pharmacokinetic (PK) analysis will be obtained on Day 0 at 1, 2, 4, and 6 hours post-application, at 24 hours' post-application (Day 1), and at each subsequent clinic visit (samples on Days 7, 14, and 21 will be obtained prior to dose application).	49 days
Secondary	Pharmacokinetics: Time at which peak plasma concentration is observed (Tmax) of SOR007	Plasma samples for pharmacokinetic (PK) analysis will be obtained on Day 0 at 1, 2, 4, and 6 hours post-application, at 24 hours' post-application (Day 1), and at each subsequent clinic visit (samples on Days 7, 14, and 21 will be obtained prior to dose application).	49 days
Secondary	Regression of CIN	Colposcopic changes as defined by the modified Reid Colposcopic Index (RCI) and confirmed by biopsy histology	Baseline and 49 days