This is a multi-center phase II trial of intravenous (IV) Pembrolizumab MK-3475 in subjects older than 70 years with advanced Non-small cell Lung Cancer (NSCLC) expressing Programmed death-ligand 1 (PD-L1). 82 patients will be enrolled in this trial to examine the efficacy, the impact on geriatric assessments, the quality of life and the self-reported outcomes.
Subjects will receive MK-3475 at a fixed dose of 200 mg every 3 weeks (Q3W) (Figure 1). Subjects will be evaluated every 9 weeks (63 ± 7 days) with radiographic imaging to assess response to treatment. QoL and Self-reported Health Questionnaires, as well as geriatric follow-up will be performed at the same intervals. Investigators will make all treatment-based decisions using immune-related Response Criteria (irRC). However, for determination of overall response rate (ORR) and progression-free survival (PFS), the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used. Adverse events will be monitored throughout the trial and graded in severity according to the guidelines outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment with MK-3475 will continue until two years of therapy have been administered, documented disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, noncompliance with trial treatment or procedure requirements, or administrative reasons. After the end of treatment, each subject will be followed for a minimum of 30 days for adverse event monitoring (serious adverse events will be collected for up to 90 days after the end of treatment unless the subject starts a new anticancer therapy between days 31 and 90). Subjects will have post-treatment follow-up for disease status, including initiating a non-study cancer treatment and experiencing disease progression, until death, withdrawing consent, or becoming lost to follow-up. Participation in this trial will be dependent upon supplying tumor tissue from a newly obtained formalin-fixed specimen from locations not radiated prior to biopsy. The specimen will be evaluated at a central laboratory facility for expression status of Programmed death-ligand 1(PD-L1) in a prospective manner. Only subjects whose tumors express Programmed death-ligand 1(PD-L1) as determined by the central laboratory facility will be eligible for inclusion in this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
83
Pembrolizumab (MK-3475) 200 mg, every 3 weeks
ICO-Hospitalet
L'Hospitalet de Llobregat, Barcelona, Spain
Consorci Sanitari de Terrassa
Terrassa, Barcelona, Spain
Hospital Universitario Sta Lucia
Cartagena, Murcia, Spain
Overall Survival
Defined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.
Time frame: From the date of inclusion of the first patient to until end of follow up, up to 36 months.
Changes in Health-related Quality of Life With Lung Cancer Symptom Scale
To evaluate changes in health-related quality of life in responder and non-responder patients older than 70 years with advanced non-small cell lung cancer. QLQ-C30 Quality of Life Questionnaire. The EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) is designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of multi-item scales and single items. All EORTC QLQ-C30 scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptom- atology
Time frame: Beginning of cycle 1 (week 1) and beginning of cycle 18 (week 54) (each cycle is 3 weeks)
Impact on Functional Assessments Measured With Barthel Scale
To evaluate the impact on functional geriatric assessments of patients older than 70 years with advanced non-small cell lung cancer. The Barthel Index assesses activities in two major categories: Personal care and mobility. The personal care items include tasks such as drinking from a cup, dressing, grooming, bathing, and bowel and bladder continence. The scoring is as follows: scores of 0-20 indicate "total" dependency. scores of 21-60 indicate "severe" dependency. scores of 61-90 indicate "moderate" dependency. scores of 91-99 indicate "slight" dependency, score of 100 indicate independent.
Time frame: Beginning of cycle 1 (week 1), beginning of cycle 4 (week 12), beginning of cycle 7 (week 21), beginning of cycle 10 (week 30), beginning of cycle 13 (week 39), beginning of cycle 16 (week 48) and beginning of cycle 18 (week 54) (each cycle is 3 weeks)
Progression-free Survival (PFS)
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Hospital Lluís Alcanyís
Xàtiva, Valencia, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Virgen de la Luz
Cuenca, Spain
Hospital Lucus Agustí
Lugo, Spain
Fundación Jiménez Díaz
Madrid, Spain
Hospital Clínico San Carlos
Madrid, Spain
Hospital Dr. Peset
Valencia, Spain
...and 2 more locations
To describe Progression-free Survival (PFS), according to RECIST criteria v. 1.1 of the first-line treatment with pembrolizumab (MK-3475) in elderly patients with advanced NSCLC. PFS defined as the length of time from the date of randomization to the date of the first documented progression of disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: From the inclusion date in the study until first progression or end of follow up, up to 36 months
Overall Survival Rate at 2 Years.
To evaluate the overall survival percentage of the patients included at two years
Time frame: From the date of inclusion of the first patient until two years follow up visit, up to 24 months
OS for Patients With a PD-L1 Under 50%
Defined as the length of time from the date of the start of the treatment that patients diagnosed with the disease and PD¨-L1 under 50% are still alive.
Time frame: From the initiation of treatment until end of follow up, up to 36 months
OS for Patients With a PD-L1 Greater Than or Equal to 50%
Defined as the length of time from the start of the treatment that patients diagnosed with the disease and PD-L1 greater than or equal to 50% are still alive.
Time frame: From the initiation of treatment until end of follow up, up to 36 months