Back to resultsPembro+Chemo in Brain Mets
Primary Purpose
Lung Cancer, Lung Cancer Metastatic, Brain Cancer
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Nab paclitaxel
Paclitaxel
Pemetrexed
Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Lung Cancer
Eligibility Criteria
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
Sites / Locations
- University of Kentucky, Markey Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pembrolizumab with standard of care chemotherapy treatment
Arm Description
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).
Outcomes
Primary Outcome Measures
Disease control rate
Intracranial benefit defined as stable disease, partial response, and complete response
Secondary Outcome Measures
Overall survival at 12-month post-enrollment
Overall survival at 12-month post-enrollment
Change in extracranial disease control
Kaplan-Meier estimates will be calculated for progression-free survival along with estimates of median survival time and proportion of surviving at specific time points (6 and 12 months).
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04964960
Brief Title
Pembro+Chemo in Brain Mets
Official Title
Phase II Investigation of Use of CNS Active Pembrolizumab and Chemotherapy for Asymptomatic Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2022 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
May 2033 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
John L. Villano, MD, PhD
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Lung Cancer Metastatic, Brain Cancer, Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pembrolizumab with standard of care chemotherapy treatment
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab is an immunotherapy that can help fight certain cancers.
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Disease control rate
Description
Intracranial benefit defined as stable disease, partial response, and complete response
Time Frame
6 months (baseline to 6 months)
Secondary Outcome Measure Information:
Title
Overall survival at 12-month post-enrollment
Description
Overall survival at 12-month post-enrollment
Time Frame
12 months (6 months post-enrollment, 12 months post-enrollment)
Title
Change in extracranial disease control
Description
Kaplan-Meier estimates will be calculated for progression-free survival along with estimates of median survival time and proportion of surviving at specific time points (6 and 12 months).
Time Frame
12 months (6 months post-enrollment, 12 months post-enrollment)
Title
Change in patient-reported cognitive functioning - Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog)
Description
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.
Time Frame
12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
Title
Change in quality of life - Functional Assessment of Cancer Therapy-Brain (FACT-Br)
Description
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.
Time Frame
12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
Title
Change in quality of life - FACIT Fatigue Scale (FACIT-F)
Description
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.
Time Frame
12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
Title
Change in mild cognitive impairment (MoCA)
Description
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.
Time Frame
12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
Title
Change in performance status
Description
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.
Time Frame
12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
Other Pre-specified Outcome Measures:
Title
Immune based biomarker activity
Description
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.
Time Frame
12 weeks (Baseline, 6 weeks after baseline, 6 weeks after prior collection)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Villano, MD, PhD
Phone
859-323-0405
Email
jlvillano@uky.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Villano, MD, PhD
Organizational Affiliation
University of Kentucky
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kentucky, Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Villano, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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Pembro+Chemo in Brain Mets
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