Clinical Trials /

Pembrolizumab for the Treatment of Cervical Intraepithelial Neoplasia

NCT04712851

Description:

This phase II trial studies the effect of pembrolizumab on cervical intraepithelial neoplasia. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Cervical Carcinoma In Situ
  • Cervical Intraepithelial Neoplasia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab for the Treatment of Cervical Intraepithelial Neoplasia
  • Official Title: A Phase II Open-Label, Single Arm Pilot Study to Evaluate the Safety and Efficacy of Pembrolizumab for High-Grade Cervical Intraepithelial Neoplasia

Clinical Trial IDs

  • ORG STUDY ID: 20-002121
  • SECONDARY ID: NCI-2020-11457
  • SECONDARY ID: 20-002121
  • NCT ID: NCT04712851

Conditions

  • Cervical Intraepithelial Neoplasia
  • Cervical Squamous Cell Carcinoma In Situ
  • Cervical Squamous Intraepithelial Neoplasia 2

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

This phase II trial studies the effect of pembrolizumab on cervical intraepithelial neoplasia. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Proportion of subjects with pathologic complete response (no evidence of dysplasia).

      SECONDARY OBJECTIVES:

      I. Safety and tolerability of pembrolizumab in subjects with cervical intraepithelial
      neoplasia (CIN).

      II. Proportion of subjects with pathologic partial response (regression to a lower grade of
      dysplasia).

      EXPLORATORY OBJECTIVES:

      I. Evaluation of PD-L1 expression in CIN lesions as a biomarker of response to therapy.

      II. Evaluation of HPV status as a biomarker of response to therapy. III. Evaluation of HPV
      clearance as a surrogate endpoint.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats
      every 6 weeks for 4 cycles (24 weeks).
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 4 cycles (24 weeks).
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Female participants who are at least 21 years of age on the day of signing informed
             consent with active (not yet resected), histologically confirmed diagnosis of CIN
             grade 2 or 3 or carcinoma in situ (without invasive component) will be enrolled in
             this study. Subjects with multifocal disease are acceptable

          -  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 120 days 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 or newly obtained core or excisional biopsy
             of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)
             tissue blocks are preferred to slides. Newly obtained biopsies are preferred to
             archived tissue

          -  Participants must be willing to consent to mid-study biopsy after cycle 2 of treatment
             if there is an accessible lesion and biopsy is not contraindicated

          -  Participants must be willing to consent to either loop electrode excision procedure
             (LEEP) or cold-knife cone (CKC) at the end of treatment (i.e., after 24 weeks on
             study), unless surgery is contraindicated at that time

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          -  Have normal organ function (with all baseline laboratory assessments in the normal
             range). Specimens must be collected within 10 days prior to the start of study
             treatment, except for pregnancy test which must be within 72 hours of cycle 1 of
             treatment

        Exclusion Criteria:

          -  A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
             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 anti PD L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
             CTLA-4, OX 40, CD137)

          -  Has received prior systemic therapy for CIN including investigational agents within
             the prior 4 weeks [could consider shorter interval for short half-life drugs] prior to
             allocation.

               -  Note: Participants must have recovered from all adverse events (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 intervention.
             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-central nervous system
             (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-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (e.g., 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 intervention.

               -  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

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug

          -  Has a history of a second malignancy, unless potentially curative treatment has been
             completed with no evidence of malignancy for 2 years.

               -  Note: The time requirement does not apply to participants who underwent
                  successful definitive resection of basal cell carcinoma of the skin, squamous
                  cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer,
                  or other in-situ cancers

          -  Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment and is allowed

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a known history of human immunodeficiency virus (HIV) infection

               -  Note: No HIV testing is required unless mandated by local health authority

          -  Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]
             reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA]
             [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C
             is required unless mandated by local health authority

          -  Has a known history of active TB (Bacillus tuberculosis)

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of trial treatment

          -  Has had an allogenic tissue/solid organ transplant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological response rate
Time Frame:At 6 months
Safety Issue:
Description:Will assess the percent of patients with pathologic complete response at 6 months.

Secondary Outcome Measures

Measure:Proportion of subjects with pathologic partial response (regression to a lower grade of dysplasia)
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:Incidence of adverse events
Time Frame:Up to 6 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jonsson Comprehensive Cancer Center

Last Updated

June 1, 2021