Clinical Trials /

Pembrolizumab in Patients With Leptomeningeal Disease

NCT03091478

Description:

This is an open-label phase II study of pembrolizumab in patients with advanced solid tumors with leptomeningeal carcinomatosis (LMD). Patients may have received any number of prior therapies for their respective solid tumors, but must not have received prior anti-PD-1 therapy and developed progressive disease. Approximately 18 subjects in this study will receive pembrolizumab at a dose of 200mg intravenously (IV) every 3 weeks (Q3W) for 4 doses. In patients who derive clinical benefit from therapy, pembrolizumab may be continued until documented disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdrawal of consent, noncompliance with trial treatment or procedure requirements, or for administrative reasons.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Patients With Leptomeningeal Disease
  • Official Title: Pembrolizumab in Patients With Leptomeningeal Disease

Clinical Trial IDs

  • ORG STUDY ID: J16156
  • SECONDARY ID: IRB00116423
  • NCT ID: NCT03091478

Conditions

  • Patients With Leptomeningeal Disease

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab 200 mg

Purpose

This is an open-label phase II study of pembrolizumab in patients with advanced solid tumors with leptomeningeal carcinomatosis (LMD). Patients may have received any number of prior therapies for their respective solid tumors, but must not have received prior anti-PD-1 therapy and developed progressive disease. Approximately 18 subjects in this study will receive pembrolizumab at a dose of 200mg intravenously (IV) every 3 weeks (Q3W) for 4 doses. In patients who derive clinical benefit from therapy, pembrolizumab may be continued until documented disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdrawal of consent, noncompliance with trial treatment or procedure requirements, or for administrative reasons.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab 200 mgExperimental
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Willing and able to provide written informed consent for the trial.

          2. 18 years of age on day of signing informed consent.

          3. Histologically or cytologically confirmed solid tumor malignancy.

          4. Cytologically confirmed LMD or radiologically detectable LMD defined as either/or:

             A measurable lesion on contrast-enhanced MRI of either the Brain or Total Spine
             greater than 3mm that has not been radiated within the last 3 months prior to
             commencement of study therapy.

             Positive CSF cytology

          5. Patients may be newly diagnosed or have received any number of lines of prior anti
             cancer therapy. However, patients are required to have received available therapies
             for their primary disease, as deemed appropriate by the treating investigator.

          6. Non escalating steroid requirement at the time of consent and study drug initiation
             for the treatment of CNS symptoms.

          7. Local radiation therapy (RT) is allowed as needed to manage symptoms appropriately, as
             long as there remains a measurable lesion in the CNS.

          8. Whole brain RT may be used, without a pre-defined washout period, prior to
             commencement of study therapy if the lesion that has been radiated is not the sole
             measurable lesion, or the patient is eligible based on positive CSF cytology.

          9. Patients may continue therapy with a targeted agent if CNS disease developed while
             receiving the agent, and for defined regimens that have been deemed safe when combined
             with anti PD 1 therapy.

         10. Be willing to provide tissue from an archival tissue specimen in selected patients,
             where available.

         11. Have a performance status of 0 or 1 on the ECOG Performance Scale.

         12. Demonstrate adequate organ function as defined in Table 3, all screening labs should
             be performed within 10 days of treatment initiation.

             Table 3.

         13. 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.

         14. Female subjects of childbearing potential (Section 4.8.2) must be willing to use an
             adequate method of contraception as outlined in Section 4.8.2 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.

         15. Male subjects of childbearing potential (Section 4.8.2) must agree to use an adequate
             method of contraception as outlined in Section 4.8.2 Contraception, starting with the
             first dose of study therapy through 120 days after the last dose of study therapy.

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

        Exclusion Criteria:

          1. 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 or 5 half lives of the first dose of treatment, whichever is
             shorter.

          2. 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.

          3. Has a known history of active TB (Bacillus Tuberculosis)

          4. Hypersensitivity to pembrolizumab or any of its excipients.

          5. 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.

          6. Has had prior chemotherapy, targeted small molecule therapy other than pre specified
             allowed agents detailed in section 4.2.6, 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.

          7. All major surgery including prior surgery to the brain within 3 weeks of commencement
             of study therapy.

          8. 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.

          9. Subjects with previously treated brain metastases may participate provided they are
             not using escalating steroids for brain metastases at the time of trial consent and
             study drug initiation, and there remains a measurable lesion in the CNS, as per
             section 4.2.6.

         10. 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.

         11. Has history of (non-infectious) pneumonitis that required steroids, evidence of
             interstitial lung disease or active, non-infectious pneumonitis.

         12. Has an active infection requiring systemic therapy.

         13. Prior disease progression on anti-PD-1 therapy

         14. 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.

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

         16. 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.

         17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

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

         20. Contraindication to MRI.

         21. Patients with a condition related to their cancer or leptomeningeal disease requiring
             urgent intervention that has not been clinically managed or stabilized prior to the
             time of consent.

         22. Brain metastases with risk of mass effect that would contraindicate lumbar puncture,
             as detailed in section 6.1.2.8.3.

         23. Live vaccines within 30 days prior to the first dose of trial treatment. 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:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with a response
Time Frame:at 12 weeks/after 4 cycles of therapy
Safety Issue:
Description:Participants will be assessed radiographically at 12 weeks

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last Updated