Pembrolizumab in Patients With Leptomeningeal Disease

NCT03091478 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: J16156IRB00116423
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label phase II study of pembrolizumab in patients with advanced solid tumors with leptomeningeal carcinomatosis (LMD). Approximately 18 subjects in this study will receive pembrolizumab at a dose of 200mg intravenously (IV) every 3 weeks (Q3W) for 4 doses.

Conditions

Patients With Leptomeningeal Disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Response

  Eligible patients who receive at least one dose of pembrolizumab.

  At 12 weeks

Secondary Outcomes (2)

• CNS Progression-free Survival in Patients With LMD From Solid Tumors Receiving Pembrolizumab

  From the date of study entry until date of death from any cause, assessed up to 24 months

• Overall Survival in Patients With LMD From Solid Tumors Receiving Pembrolizumab

  From the date of study entry until date of death from any cause, assessed up to 24 months

Study Arms (1)

Pembrolizumab 200 mg

EXPERIMENTAL

Pembrolizumab 200 mg every 3 weeks

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

200mg every 3 weeks

Also known as: Keytruda

Pembrolizumab 200 mg

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent for the trial.
• years of age on day of signing informed consent.
• Histologically or cytologically confirmed solid tumor malignancy.
• 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 cerebrospinal fluid (CSF) cytology
• 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.
• Non escalating steroid requirement at the time of consent and study drug initiation for the treatment of central nervous system (CNS) symptoms.
• Local radiation therapy (RT) is allowed as needed to manage symptoms appropriately, as long as there remains a measurable lesion in the CNS.
• 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.
• 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.
• Be willing to provide tissue from an archival tissue specimen in selected patients, where available.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function as defined in Table 3, all screening labs should be performed within 10 days of treatment initiation.
• Table 3.

You may not qualify if:

• 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.
• 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 Bacillus Tuberculosis (TB)
• 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 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.
• All major surgery including prior surgery to the brain within 3 weeks of commencement of study 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.
• 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.
• 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.
• Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Prior disease progression on anti-PD-1 therapy

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Naidoo J, Schreck KC, Fu W, Hu C, Carvajal-Gonzalez A, Connolly RM, Santa-Maria CA, Lipson EJ, Holdhoff M, Forde PM, Douville C, Riemer J, Barnes A, Redmond KJ, Kleinberg L, Page B, Aygun N, Kinzler KW, Papadopoulos N, Bettegowda C, Venkatesan A, Brahmer JR, Grossman SA. Pembrolizumab for patients with leptomeningeal metastasis from solid tumors: efficacy, safety, and cerebrospinal fluid biomarkers. J Immunother Cancer. 2021 Aug;9(8):e002473. doi: 10.1136/jitc-2021-002473.

  PMID: 34380662 DERIVED

MeSH Terms

Interventions

pembrolizumab

Results Point of Contact

• Title: Rachel Levy, MS, CCRP
• Organization: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

rlevy16@jhmi.edu

410-502-8738

Study Officials

• Jarushka Naidoo, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: March 27, 2017
• Study Start: April 12, 2017
• Primary Completion: December 14, 2019
• Study Completion: December 14, 2019
• Last Updated: January 26, 2021
• Results First Posted: January 26, 2021

Record last verified: 2021-01

Locations

US (1)