Pembro+Chemo in Brain Mets

Phase 2

Terminated

Conditions: Lung Cancer
Lung Cancer Metastatic
Brain Cancer
Cancer

Interventions: Drug: Pembrolizumab
Drug: Nab paclitaxel
Drug: Paclitaxel
Drug: Pemetrexed
Drug: Carboplatin

Registration Number: NCT04964960

Lead Sponsor: John L. Villano, MD, PhD

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pembrolizumab with standard of care chemotherapy treatment	Nab paclitaxel	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 with standard of care chemotherapy treatment	Pembrolizumab	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 with standard of care chemotherapy treatment	Pemetrexed	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 with standard of care chemotherapy treatment	Carboplatin	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 with standard of care chemotherapy treatment	Paclitaxel	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).

Primary Outcome Measures

Name	Time	Method
Disease Control Rate	6 months (baseline to 6 months)	Intracranial benefit defined as stable disease, partial response, and complete response

Secondary Outcome Measures

Name	Time	Method
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)	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)	12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 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 - Functional Assessment of Cancer Therapy-Brain (FACT-Br)	12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 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.
Change in Quality of Life - FACIT Fatigue Scale (FACIT-F)	12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 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, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 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, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 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.