Brain Cancer, Cancer, Lung Cancer, Lung Cancer Metastatic
Conditions
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.
Interventions
DRUGPembrolizumab
Pembrolizumab is an immunotherapy that can help fight certain cancers.
DRUGNab paclitaxel
Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly.
DRUGPaclitaxel
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.
DRUGPemetrexed
Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication.
DRUGCarboplatin
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.
Sponsors
John L. Villano, MD, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | 6 months (baseline to 6 months) | Intracranial benefit defined as stable disease, partial response, and complete response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Survival at 12-month Post-enrollment | 12 months | Overall survival at 12-month post-enrollment |
| Change in Extracranial Disease Control | 12 months (6 months post-enrollment, 12 months post-enrollment) | Extracranial disease control rate (systemic): includes stable disease, partial response, and complete response. |
| Change in Patient-reported Cognitive Functioning - Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) | 12 months (Baseline and 12 months post enrollment) | 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 - FACIT Fatigue Scale (FACIT-F) | 12 months (Baseline and 12 months post enrollment) | 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) | 12 months (Baseline and 12 months post enrollment) | 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 | 12 months (Baseline and 12 months post enrollment) | 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. |
| Change in Quality of Life - Functional Assessment of Cancer Therapy-Brain (FACT-Br) | 12 months (Baseline and 12 months post enrollment) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immune Based Biomarker Activity | 12 weeks (Baseline, 6 weeks after baseline, 6 weeks after prior collection) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
Pembrolizumab: Pembrolizumab is an immunotherapy that can help fight certain cancers.
Nab paclitaxel: Nab-paclitaxel is a taxane derivative that is an albumin-bound paclitaxel nanoparticle formulation that promotes microtubule assembly.
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.
Pemetrexed: Pemetrexed is an antifolate agent that disrupts folate-dependent metabolic processes essential for cell replication.
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. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not complete cycles | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Pembrolizumab with standard of care chemotherapy treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 3 |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Disease Control Rate
Intracranial benefit defined as stable disease, partial response, and complete response
Time frame: 6 months (baseline to 6 months)
Population: Number of participants enrolled at 6 month timepoint
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab with standard of care chemotherapy treatment | Disease Control Rate | Partial Response | 0 Participants |
| Pembrolizumab with standard of care chemotherapy treatment | Disease Control Rate | Stable Disease | 0 Participants |
| Pembrolizumab with standard of care chemotherapy treatment | Disease Control Rate | Complete Response | 2 Participants |
Secondary
Change in Extracranial Disease Control
Extracranial disease control rate (systemic): includes stable disease, partial response, and complete response.
Time frame: 12 months (6 months post-enrollment, 12 months post-enrollment)
Population: participants enrolled at 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab with standard of care chemotherapy treatment | Change in Extracranial Disease Control | 1 Participants |
Secondary
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.
Time frame: 12 months (Baseline and 12 months post enrollment)
Population: participant declined to complete the questionnaire
Secondary
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.
Time frame: 12 months (Baseline and 12 months post enrollment)
Population: participant declined to complete the questionnaire
Secondary
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.
Time frame: 12 months (Baseline and 12 months post enrollment)
Population: participant declined to complete the questionnaire
Secondary
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.
Time frame: 12 months (Baseline and 12 months post enrollment)
Population: participant declined to complete the questionnaire
Secondary
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.
Time frame: 12 months (Baseline and 12 months post enrollment)
Population: participant declined to complete the questionnaire
Secondary
Number of Participants With Overall Survival at 12-month Post-enrollment
Overall survival at 12-month post-enrollment
Time frame: 12 months
Population: participants enrolled at 12 month timepoint
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab with standard of care chemotherapy treatment | Number of Participants With Overall Survival at 12-month Post-enrollment | 1 Participants |
Other Pre-specified
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.
Time frame: 12 weeks (Baseline, 6 weeks after baseline, 6 weeks after prior collection)