Clinical Trials /

Pembrolizumab for the Treatment of High-Grade Vulvar, Vaginal, or Cervical Intraepithelial Neoplasia

NCT04712851

Description:

This phase II trial studies the effect of pembrolizumab on high-grade vulvar, vaginal, and 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
  • Vaginal Intraepithelial Neoplasia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab for the Treatment of High-Grade Vulvar, Vaginal, or 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 Vulvar, Vaginal, and 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
  • Vaginal Intraepithelial Neoplasia
  • Vulvar Intraepithelial Neoplasia

Interventions

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

Purpose

This phase II trial studies the effect of pembrolizumab on high-grade vulvar, vaginal, and 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. Clinical response rate at 6 months - percent of patients with complete response at 6
      months.

      SECONDARY OBJECTIVES:

      I. Histologic response rate at 6 months - percent of patients with regression from grade 2 or
      3 intraepithelial neoplasia or carcinoma in situ to a lower grade.

      II. Clinical complete response rate at 9 months and 12 months. III. For vulvar
      intraepithelial neoplasia (VIN) only, clinical partial response rate at 6 months, 9 months,
      and 12 months.

      IV. Safety and tolerability of pembrolizumab in patients with VIN, vaginal intraepithelial
      neoplasia (VaIN), and cervical intraepithelial neoplasia (CIN).

      EXPLORATORY OBJECTIVES:

      I. Evaluation of PD-L1 expression in VIN, VaIN, and 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 a minimum of 24 weeks (4 cycles) and up to a maximum of 24 months in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 8 weeks for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for a minimum of 24 weeks (4 cycles) and up to a maximum of 24 months in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab

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 VIN, vaginal intraepithelial
             neoplasia (VaIN), or cervical intraepithelial neoplasia (CIN) grade 2 or 3 or
             carcinoma in situ (without invasive component) will be enrolled in this study

          -  A female participant is eligible to participate if she is not pregnant (see Appendix
             3), 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 visible disease on physical exam and/or colposcopy

          -  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

          -  For subjects with VaIN or CIN only, participants must be willing to consent to
             end-of-study biopsy after cycle 4 of treatment if there is an accessible lesion and
             biopsy is not contraindicated

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
             Evaluation of ECOG is to be performed within 7 days prior to the date of
             allocation/randomization

          -  Absolute neutrophil count (ANC) >= 1500/microliter (uL)(specimens must be collected
             within 10 days prior to the start of study treatment)

          -  Platelets >= 100 000/uL (specimens must be collected within 10 days prior to the start
             of study treatment)

          -  Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (specimens must be collected within 10 days
             prior to the start of study treatment)

               -  Criteria must be met without erythropoietin dependency and without packed red
                  blood cell (pRBC) transfusion within last 2 weeks

          -  Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine
             clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or
             creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5
             x institutional ULN (specimens must be collected within 10 days prior to the start of
             study treatment)

               -  Creatinine clearance (CrCl) should be calculated per institutional standard

          -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total
             bilirubin levels > 1.5 x ULN (specimens must be collected within 10 days prior to the
             start of study treatment)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
             ULN (specimens must be collected within 10 days prior to the start of study treatment)

          -  International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless
             participant is receiving anticoagulant therapy as long as PT or aPTT is within
             therapeutic range of intended use of anticoagulants (specimens must be collected
             within 10 days prior to the start of study treatment)

          -  Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is
             receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of
             intended use of anticoagulants (specimens must be collected within 10 days prior to
             the start of study treatment)

          -  The participant is willing to consent to photographs of lesions

        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 (eg, CTLA-4,
             OX 40, CD137)

          -  Has received prior systemic therapy for VIN, VaIN, or 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 (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 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:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Histologic response rate
Time Frame:At 6 months
Safety Issue:
Description:Will assess the percent of patients with regression from grade 2 or 3 intraepithelial neoplasia or carcinoma in situ to a lower grade.
Measure:Clinical complete response rate
Time Frame:At 9 and 12 months
Safety Issue:
Description:
Measure:Clinical partial response rate (for vulvar intraepithelial neoplasia [VIN] only)
Time Frame:At 6, 9, and 12 months
Safety Issue:
Description:
Measure:Number of participants with treatment related adverse events as assessed by CTCAE v5.0.
Time Frame:Up to 12 months
Safety Issue:
Description:Safety and tolerability of pembrolizumab

Details

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

Last Updated

January 15, 2021