Clinical Trials /

Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors

NCT03274661

Description:

Phase II trial in which patients with metastatic solid tumors experiencing progression after first line standard chemotherapy or for which there is no standard chemotherapy, and for which pembrolizumab does not have an FDA or compendia listing approved indication, will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.

Related Conditions:
  • Endometrial Carcinoma
  • Malignant Solid Tumor
  • Uterine Corpus Endometrial Stromal Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors
  • Official Title: Evaluating Immune Checkpoint Inhibition In Solid Tumor Patients With Homologous Recombination Repair Deficiency

Clinical Trial IDs

  • ORG STUDY ID: MK-3475-663
  • NCT ID: NCT03274661

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
Pembrolizumab 200 mg Q3WPembrolizumab 200 mgPembrolizumab 200 mg Q3W

Purpose

Phase II trial in which patients with metastatic solid tumors experiencing progression after first line standard chemotherapy or for which there is no standard chemotherapy, and for which pembrolizumab does not have an FDA or compendia listing approved indication, will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.

Detailed Description

      Patients with metastatic or recurrent solid malignancy who have progressed on first line
      standard of care treatment or for which defined standard of care does not exist or is not
      readily available are eligible to participate on this trial. Patients for which pembrolizumab
      has an FDA approved indication and for whom pembrolizumab is covered by their insurance
      should receive standard commercial pembrolizumab and will not be eligible for this trial.

      The primary objective of this trial is to evaluate the Immune-Related Objective Response Rate
      (IR-ORR) achieved with pembrolizumab in patients with Fanconi Anemia Repair Pathway
      functionally competent and functionally deficient tumors.

      Trial treatment should be administered on Day 1 of each cycle after all
      procedures/assessments have been completed. Trial treatment may be administered up to 3 days
      before or after the scheduled Day 1 of each cycle due to administrative reasons.

      All trial treatments will be administered on an outpatient basis.

      Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Target
      infusion timing is 30 minutes.

      Expansion Cohort:

      Ten (10) additional subjects with the diagnosis of metastatic or recurrent endometrial
      carcinoma will be enrolled in the trial at the conclusion of regular enrollment.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab 200 mg Q3WExperimentalPembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle
  • Pembrolizumab 200 mg Q3W

Eligibility Criteria

        Inclusion Criteria:

          -  Have measurable disease based on RECIST 1.1.

          -  Be willing to provide consent for retrieval of archival tumor material tissue from a
             previously obtained core or excisional biopsy of a tumor lesion.

          -  Have a tumor presentation at screening for which pembrolizumab does not have an FDA
             approved indication for commercial use.

          -  Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.

          -  Demonstrate adequate organ function

          -  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.

        Expansion cohort - additional criteria

          1. Diagnosis of Endometrial Carcinoma or Sarcoma which is metastatic and has failed
             standard treatment or is recurrent, or for which standard chemotherapy is
             contraindicated or refused by patient.

          2. Sufficient tissue is available for correlative studies

          3. MSI studies have been performed, either by immunohistochemistry or next generation
             sequencing and results show that patient is MS low or stable.

        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 4 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 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 a known history of active Bacillus Tuberculosis

          -  Hypersensitivity to pembrolizumab or any of its excipients.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable. 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).

          -  Has immunohistochemically proven mismatch repair deficient cancer

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

          -  Evidence of interstitial lung disease.

          -  Has an active infection requiring systemic therapy.

          -  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., HBsAg reactive) or Hepatitis C (e.g., HCV 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:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:immune-related objective response rate
Time Frame:every 2 cycles (3 weeks cycles); that is before every third dose of pembrolizumab
Safety Issue:
Description:Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy.

Secondary Outcome Measures

Measure:20-week immune-related progression-free survival rate
Time Frame:20-week
Safety Issue:
Description:Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Baptist Health South Florida

Trial Keywords

  • solid tumor, Pembrolizumab,

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