Single Arm Phase II Study on Pembrolizumab in Pre Neoplastic High Grade HPV-related Vulvar and Cervical Lesions

Fondazione Policlinico Universitario Agostino Gemelli IRCCS9 sites in 1 country45 target enrollmentOctober 14, 2020

ConditionsCervical, Vaginal and Vulval Inflammatory Diseases

InterventionsPembrolizumab

DrugsPembrolizumab

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Cervical, Vaginal and Vulval Inflammatory Diseases
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Enrollment: 45
Locations: 9
Primary Endpoint: Efficacy of Pembrolizumab: proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment
Status: Recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

single arm phase II trial evaluating Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy in patients with pre-neoplastic cervical and vulvar high grade lesions.

Detailed Description

This is a single arm phase II trial evaluating Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy in patients with pre-neoplastic cervical and vulvar high grade lesions. Patients with histologically confirmed H-SIL and/or VIN 2-3 lesions will be treated with Pembrolizumab 200 mg flat dose every 3 weeks for 5 cycles. Within 3 weeks from the last Pembrolizumab administration patients will be submitted to surgical conization or partial or radical vulvectomy.

Registry

clinicaltrials.gov

Start Date

October 14, 2020

End Date

September 1, 2024

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of cervical HSIL OR vulvar VIN 2-3 lesions will be enrolled in this study.
•A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
•Not a woman of childbearing potential (WOCBP) OR
•A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of study treatment.
•The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
•Have provided archival tumor tissue sample (if pre treatment biopsy performed at other institution) or newly obtained core or excisional biopsy of the lesion. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
•Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
•Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
•Evaluation of ECOG is to be performed within 7 days prior to the date of registration .
•Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.

Exclusion Criteria

•A WOCBP who has a positive urine pregnancy test within 72 hours prior to study drug treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
•Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
•Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
•Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to \[randomization /allocation\].
•Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
•Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
•Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
•Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
•Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
•Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

Arms & Interventions

Pembrolizumab single agent

Pembrolizumab single agent as neoadjuvant treatment before surgical conization and/or partial or radical vulvectomy. Pembrolizumab 200 mg flat dose will be administered every 3 weeks for 5 cycles. Within 3 weeks from the last Pembrolizumab administration patients will be submitted to surgical conization or partial or radical vulvectomy.

Intervention: Pembrolizumab

Outcomes

Primary Outcomes

Efficacy of Pembrolizumab: proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment

Time Frame: 18 months

proportion of subjects with no evidence of cervical HSIL on histology at surgical treatment

Secondary Outcomes

Efficacy of Pembrolizumab: Proportion of subjects with no progression of cervical HSIL and vulvar VIN 2-3 to cervical and vulvar carcinoma respectively from baseline on histology(18 months)
Efficacy of Pembrolizumab: Incidence and severity of systemic events for the duration of the study (CTCAE 5.0)(18 months)
Efficacy of Pembrolizumab: Proportion of subjects with downstaging of cervical and vulvar pre-neoplastic lesion on histology(18 months)
Efficacy of Pembrolizumab: Proportion of subjects with no evidence of vulvar VIN 2-3 on histology at surgical treatment(18 months)
Efficacy of Pembrolizumab: Proportion of patients with no evidence of HPV by HPV testing at Week 36 visit(18 months)