Clinical Trials /

Pembrolizumab in Treating Participants With Recurrent Ovarian Cancer

NCT03732950

Description:

This phase II trial studies how well pembrolizumab works in treating participants with ovarian cancer that has come back after previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Participants With Recurrent Ovarian Cancer
  • Official Title: A Phase II Study of Pembrolizumab Monotherapy in Recurrent Ovarian Cancer of the Immunoreactive Subtype Determined by NanoString Gene Expression Profiling

Clinical Trial IDs

  • ORG STUDY ID: 18-000643
  • SECONDARY ID: NCI-2018-01550
  • SECONDARY ID: 18-000643
  • SECONDARY ID: P30CA016042
  • NCT ID: NCT03732950

Conditions

  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma

Interventions

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

Purpose

This phase II trial studies how well pembrolizumab works in treating participants with ovarian cancer that has come back after previous treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate clinical anti-tumor activity of pembrolizumab monotherapy based on objective
      response rate (ORR) as assessed by the investigator per immune related Response Evaluation
      Criteria in Solid Tumors (irRECIST) in patients with recurrent ovarian cancer (ROC) whose
      tumors show an immunoreactive gene expression signature.

      SECONDARY OBJECTIVES:

      I. To evaluate clinical anti-tumor activity of pembrolizumab monotherapy based on
      progression-free survival (PFS) as assessed by the investigator per irRECIST in patients with
      ROC whose tumors show an immunoreactive gene expression signature.

      II. To evaluate clinical anti-tumor activity of pembrolizumab monotherapy based on PFS rate
      at 6, 12 and 18 months as assessed by the investigator per irRECIST in patients with ROC
      whose tumors show an immunoreactive gene expression signature.

      III. To evaluate and characterize the tolerability and safety profile of the study population
      after being treated with pembrolizumab as monotherapy.

      EXPLORATORY OBJECTIVES:

      I. To assess correlations of the immunoreactive gene signature with the validated a PD-L1
      immunohistochemistry (IHC) assay using Merck's proprietary 22C3 antibody and the clinical
      activity observed in the study population.

      OUTLINE:

      Participants receive pembrolizumab intravenously (IV) on day 1. Courses repeat every 3 weeks
      for up to 35 courses (2 years) in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, participants are followed up at 30 and then every 9 and
      12 weeks thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalParticipants receive pembrolizumab intravenously IV on day 1. Courses repeat every 3 weeks for up to 35 courses (2 years) in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Have received 1-5 prior lines for treating ROC (i.e. 2-6 total prior lines counting
             the front line) and must have a platinum-free interval (PFI) or a treatment-free
             interval (TFI) >= 3 months based on the last regimen received

          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
             1.1

               -  Note: Tumor lesions situated in a previously irradiated area are considered
                  measurable if progression has been demonstrated in such lesions

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Have histologically diagnosed recurrent epithelial ovarian, fallopian or primary
             peritoneal ovarian cancer

          -  Have provided a tumor tissue sample either collected from a newly obtained tumor
             tissue biopsy or an archival tissue specimen. Subjects for whom newly obtained samples
             cannot be provided (e.g. inaccessible or subject safety concern) may submit an
             archived biopsy specimen. Formalin-fixed paraffin embedded (FFPE) block specimens are
             preferred to 20 unstained slides. Additional samples may be requested if tumor tissue
             provided is not adequate for quality and/or quantity as assessed by the central
             laboratory

          -  Performed within 10 days of treatment initiation: absolute neutrophil count (ANC) >=
             1,500/mcL

          -  Performed within 10 days of treatment initiation: platelets >= 100,000/mcL

          -  Performed within 10 days of treatment initiation: hemoglobin >= 9 g/dL or >= 5.6
             mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of
             assessment)

          -  Performed within 10 days of treatment initiation: serum creatinine OR measured or
             calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be
             used in place of creatinine or CrCl) =< 1.5 x upper limit of normal (ULN) OR >= 45
             mL/min for subject with creatinine levels > 1.5 x institutional ULN

               -  Creatinine clearance should be calculated per institutional standard

          -  Performed within 10 days of treatment initiation: serum total bilirubin =<1.5 x ULN OR
             direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN

          -  Performed within 10 days of treatment initiation: aspartate aminotransferase (AST)
             (serum glutamate pyruvate transaminase [SGOT]) and aspartate aminotransferase (ALT)
             (serum glutamic-oxaloacetic transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for
             subjects with liver metastases

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Have received front line platinum-based chemotherapy (preoperative chemotherapy is
             allowed)

          -  Female subjects of childbearing potential must be willing to use an adequate method of
             contraception for the course of the study through 120 days after the last dose of
             study medication

               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred
                  contraception for the subject

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 2 weeks of the first dose of treatment

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment

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

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at
             baseline) from adverse events due to a previously administered agent

               -  Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting therapy

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability

          -  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 (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment

          -  Has known history of, or any evidence of active, non-infectious pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject?s
             participation for the full duration of the trial, 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 trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected)

          -  Has received a live vaccine within 30 days of planned start of study therapy

               -  Note: Seasonal influenza vaccines for injection are generally inactivated flu
                  vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)
                  are live attenuated vaccines, and are not allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR) assessed per immune related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR will be calculated with corresponding 95% unadjusted exact binomial confidence interval (CI).

Secondary Outcome Measures

Measure:Progression-free survival (PFS) assessed per irRECIST
Time Frame:At 6, 12, and 18 months
Safety Issue:
Description:The Kaplan?Meier method will be used to summarize PFS and PFS at 6 months.
Measure:Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jonsson Comprehensive Cancer Center

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