Pembro+Chemo in Brain Mets

Phase II Investigation of Use of CNS Active Pembrolizumab and Chemotherapy for Asymptomatic Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)

The goal of this study is to evaluate whether providing Pembrolizumab prolongs survival and preserves quality of life while minimizing side effects for patients with NSCLC with untreated asymptomatic brain metastasis.

Study Overview

• Status: Terminated
• Conditions: Cancer; Lung Cancer; Lung Cancer Metastatic; Brain Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Nab paclitaxel; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky, Markey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Non-small cell lunch cancer (NSLC) with untreated asymptomatic brain metastases
• NSLC lacks oncogenic driver mutations
• Absence of new onset neurological symptoms
• Presence of fewer than ten intracranial lesions
• Each lesion measures three centimeters or less
• Life expectancy of greater than three months
• Adequate organ and marrow function
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

• Presence of oncogenic driver mutations
• Measurable lesion located within 10mm of the optic chiasm or optic nerve, or within the brainstem
• Known leptomeningeal involvement.
• Midline shift
• Serious non-healing wound, ulcer or bone fracture
• Baseline inability to participate or complete neurocognitive testing
• Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury within 14 days prior to registration
• Receipt of a non-CNS minor surgical procedure (e.g. core biopsy or fine needle aspiration) within three days prior to registration
• History of allergic reactions attributed to monoclonal antibodies (mAb), compounds of similar chemical or biologic composition to Pembrolizumab
• Clinically significant cardiovascular disease
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pembrolizumab with standard of care chemotherapy treatment; Patients will receive 200mg or 400mg of Pembrolizumab (standard of care dosing at the discretion of treating physician) over thirty minutes on day 1 every three or six weeks with standard of care chemotherapy treatment (carboplatin, pemetrexed, paclitaxel, nab-paclitaxel).

Drug: Pembrolizumab; Pembrolizumab is an immunotherapy that can help fight certain cancers.; Other Names: Keytruda; Drug: Nab paclitaxel; Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly.; Drug: Paclitaxel; Paclitaxel is a taxane derivative that promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication.; Drug: Pemetrexed; Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication.; Drug: Carboplatin; Carboplatin is a platinum compound alkylating agent which covalently binds to DNA and interferes with the function of DNA by producing interstrand DNA cross-links.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	Intracranial benefit defined as stable disease, partial response, and complete response	6 months (baseline to 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Overall Survival at 12-month Post-enrollment	Overall survival at 12-month post-enrollment	12 months
Change in Extracranial Disease Control	Extracranial disease control rate (systemic): includes stable disease, partial response, and complete response.	12 months (6 months post-enrollment, 12 months post-enrollment)
Change in Patient-reported Cognitive Functioning - Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog)	The FACT-Cog questionnaire was developed to assess perceived cognitive function and impact on quality of life (QOL) in cancer patients. The level of perceived cognitive impairments is measured on a four-point Likert scale (4 = several times a day to 0 = never) FACT-Cog has been widely administered across clinical settings and validated across different cultures and languages. Subjects can complete it in 5 minutes. A higher score indicates a better quality of life/cognitive function.	12 months (Baseline and 12 months post enrollment)
Change in Quality of Life - Functional Assessment of Cancer Therapy-Brain (FACT-Br)	The FACT-Br is a commonly used instrument measuring general quality of life (QOL) that reflects symptoms or problems associated with brain malignancies across 5 subscales. The level of well-being is measured on a four-point Likert scale (4 = very much to 0 = not at all). The measure yields information about total quality of life, as well as information about the dimensions of physical well-being, social/family well-being, emotional well-being, functional well-being, and disease-specific concerns. The score range is 0-200 where a higher score indicated a better quality of life. The FACT-Br is written at the 4th grade reading level, and subjects can complete it in 5-10 minutes.	12 months (Baseline and 12 months post enrollment)
Change in Quality of Life - FACIT Fatigue Scale (FACIT-F)	FACIT-F is a short, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued) with a score range of 0-52. Subjects can complete the questionnaire in 2-3 minutes and the higher the score, the better the quality of life.	12 months (Baseline and 12 months post enrollment)
Change in Mild Cognitive Impairment (MoCA)	Neurocognitive functioning will be evaluated utilizing the Montreal Cognitive Assessment (MoCA). MoCA assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Participants will complete the MoCA (estimated time 10 minutes). The MoCA is scored to obtain an item total, scores can range from 0 to 30 and score of 26 or above is considered normal.	12 months (Baseline and 12 months post enrollment)
Change in Performance Status	Participant performance status will be evaluated utilizing the Eastern Cooperative Oncology Group (ECGO) performance status instrument. Performance status is graded from 0-5 where lower scores indicate better performance/patient daily living abilities.	12 months (Baseline and 12 months post enrollment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Based Biomarker Activity	PD-1 and several immune-based markers, such as cytotoxic T cells, will be measured and summarized descriptively. Correlations with PD-1 and between markers will be estimated using Pearson or Spearman's correlation coefficient. Exploratory association of these biological markers with DCR will be performed using two-group comparison tests. Adjustment for multiple testing due to several immune-based markers will be considered using Holm's p-value adjustment method.	12 weeks (Baseline, 6 weeks after baseline, 6 weeks after prior collection)

Collaborators and Investigators

• Sponsor: John L. Villano, MD, PhD
• Investigators: Principal Investigator: John Villano, MD, PhD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2022
• Primary Completion (Actual): June 19, 2023
• Study Completion (Actual): December 19, 2023

Study Registration Dates

• First Submitted: July 6, 2021
• First Submitted That Met QC Criteria: July 6, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Estimated): October 31, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms; Lung Neoplasms; Brain Neoplasms; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Health Care Economics and Organizations; Economics; Pemetrexed; Carboplatin; Paclitaxel; pembrolizumab; Taxes
• Other Study ID Numbers: MCC-21-NEURO-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No