Pembro+Chemo in Brain Mets

• ClinicalTrials.gov Identifier: NCT04964960
• Recruitment Status: Recruiting
• First Posted: July 16, 2021
• Last Update Posted: January 19, 2022
• Sponsor: John L. Villano, MD, PhD
• Information provided by (Responsible Party): John L. Villano, MD, PhD, University of Kentucky

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer; Lung Cancer Metastatic; Brain Cancer; Cancer	Drug: Pembrolizumab; Drug: Nab paclitaxel; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Carboplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Investigation of Use of CNS Active Pembrolizumab and Chemotherapy for Asymptomatic Brain Metastasis From Non-small Cell Lung Cancer (NSCLC)
• Actual Study Start Date: December 7, 2021
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: May 2033

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Disease control rate [ Time Frame: 6 months (baseline to 6 months) ]
   Intracranial benefit defined as stable disease, partial response, and complete response

Secondary Outcome Measures :

1. Overall survival at 12-month post-enrollment [ Time Frame: 12 months (6 months post-enrollment, 12 months post-enrollment) ]
   Overall survival at 12-month post-enrollment
2. Change in extracranial disease control [ Time Frame: 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).
3. Change in patient-reported cognitive functioning - Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) [ Time Frame: 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.
4. Change in quality of life - Functional Assessment of Cancer Therapy-Brain (FACT-Br) [ Time Frame: 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.
5. Change in quality of life - FACIT Fatigue Scale (FACIT-F) [ Time Frame: 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.
6. Change in mild cognitive impairment (MoCA) [ Time Frame: 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.
7. Change in performance status [ Time Frame: 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.

Other Outcome Measures:

1. Immune based biomarker activity [ Time Frame: 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.

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: John Villano, MD, PhD; 859-323-0405; jlvillano@uky.edu

Locations

United States, Kentucky

University of Kentucky, Markey Cancer Center; Recruiting

Lexington, Kentucky, United States, 40536

Contact: John Villano, MD, PhD

Sponsors and Collaborators

John L. Villano, MD, PhD

Investigators

• Principal Investigator: John Villano, MD, PhD; University of Kentucky

More Information

• Responsible Party: John L. Villano, MD, PhD, Principal Investigator, University of Kentucky
• ClinicalTrials.gov Identifier: NCT04964960
• Other Study ID Numbers: MCC-21-NEURO-11
• First Posted: July 16, 2021
• Last Update Posted: January 19, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Lung Neoplasms; Brain Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Pembrolizumab; Pemetrexed; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors