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Pembrolizumab in Patients With Leptomeningeal Disease

This study is currently recruiting participants.
Verified July 2017 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT03091478
First Posted: March 27, 2017
Last Update Posted: August 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
  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.

Condition Intervention Phase
Patients With Leptomeningeal Disease Drug: Pembrolizumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pembrolizumab in Patients With Leptomeningeal Disease

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of participants with a response [ Time Frame: at 12 weeks/after 4 cycles of therapy ]
    Participants will be assessed radiographically at 12 weeks


Estimated Enrollment: 18
Actual Study Start Date: April 12, 2017
Estimated Study Completion Date: May 30, 2022
Estimated Primary Completion Date: May 30, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab 200 mg Drug: Pembrolizumab
200mg every 3 weeks

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03091478


Contacts
Contact: Jarushka Naidoo, MD 410- jnaidoo1@jhmi.edu
Contact: Jessica Wakefield 410-502-3696 jrober31@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Jarushka Naidoo, MD    410-955-8893    jnaidoo1@jhmi.edu   
Contact: Jessica Wakefield    410-502-3696    jrober31@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
  More Information

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03091478     History of Changes
Other Study ID Numbers: J16156
IRB00116423 ( Other Identifier: JHU IRB )
First Submitted: January 3, 2017
First Posted: March 27, 2017
Last Update Posted: August 1, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Pembrolizumab
Antineoplastic Agents


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