Pembro+Chemo in Brain Mets

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04964960
• Other study ID #: MCC-21-NEURO-11
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 19, 2022
• Est. completion date: May 2033

Study information

• Verified date: April 2024
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3
• Est. completion date: May 2033
• Est. primary completion date: June 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Cancer
• Brain Neoplasms
• Cancer
• Lung Cancer
• Lung Cancer Metastatic
• Lung Neoplasms

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	University of Kentucky, Markey Cancer Center	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
John L. Villano, MD, PhD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	Disease control rate	Intracranial benefit defined as stable disease, partial response, and complete response	6 months (baseline to 6 months)
Secondary	Overall survival at 12-month post-enrollment	Overall survival at 12-month post-enrollment	12 months (6 months post-enrollment, 12 months post-enrollment)
Secondary	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).	12 months (6 months post-enrollment, 12 months post-enrollment)
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.	12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
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.	12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
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.	12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
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.	12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)
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.	12 months (Baseline, 3 months post-enrollment, 6 months post-enrollment, 9 months post-enrollment, 12 months post enrollment)