Pembrolizumab in Patients With Non-Small Cell Lung Cancer and a Performance Status 2

Carcinoma, Non-Small-Cell Lung Clinical Trial

— PePS2  

Official title:

A Phase II Trial of Pembrolizumab in Patients With Non-small Cell Lung Cancer and a Performance Status of 2

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02733159
• Other study ID #: RG_14-172
• Secondary ID: 2015-002241-55IS
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 7, 2016
• Est. completion date: February 7, 2024

Study information

• Verified date: November 2023
• Source: University of Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to determine that pembrolizumab is safe and tolerable at the selected dose for the treatment of Non-Small Cell Lung Cancer (NSCLC) in patients with a performance status of 2. All patients will receive pembrolizumab.

Description:

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. There are several studies which demonstrate a role for the immune system in fighting lung cancer. However, there are multiple mechanisms by which cancer dampens this response. The PD-1 receptor-ligand interaction is one of the major pathways hijacked by tumours to help evade detection and elimination by the cells of the immune system. A number of compounds which block this pathway, including the drug pembrolizumab, have shown impressive results in some patients.

At present all of the trials with pembrolizumab reported thus far have been in patients with a good Performance Status of 0-1, a measure of daily activity. Unfortunately many patients with lung cancer have impaired performance status, making them ineligible for trials of new therapies including anti PD-1. Clinical trials of standard-of-care therapy have been successfully performed in the PS=2 only population demonstrating the feasibility of performing clinical trials in this population.

In this trial, the investigators would like to determine whether this drug can be used to treat Performance status 2 patients with a lower general daily activity. The purpose of this trial is to determine that pembrolizumab is safe and tolerable. The investigators would also like to see how well the treatment works, find out more information about tumour shrinkage, and learn more about the disease and how it changes over time.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: February 7, 2024
• Est. primary completion date: February 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Core Inclusion Criteria:

• Histologically confirmed PD-L1 status defined NSCLC. Biopsy must be within 70 days of first treatment with pembrolizumab.

• ECOG performance status 2.

• Life expectancy > 12 weeks.

• Uni-dimensionally measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

• Computerised Tomography (CT) scan of chest and abdomen within 28 days of starting pembrolizumab.

• Adequate haematological function:

• Platelet count =100 x 109 /L.

• Neutrophils =1.5 x 109/L.

• Haemoglobin = 90 g/L.

• Adequate hepatic function:

• Serum bilirubin =1.5 x upper limit of normal (ULN).

• Serum transaminases =2.5 x ULN.

• Adequate renal function: Creatinine clearance <1.5 times ULN concurrent with creatinine clearance >50 ml/min.

• Provision of signed and dated, written informed consent prior to any trial specific procedures, sampling and analyses.

Core Exclusion Criteria:

• Patients who do not meet the criteria of performance status = 2 on the ECOG Performance scale.

• Untreated symptomatic brain or leptomeningeal metastatic disease.

• Medical or psychiatric conditions compromising informed consent.

• Any medical condition which in the opinion of the investigator would compromise the ability of the patient to participate in the trial or which would jeopardise compliance with the protocol.

• Radiotherapy within 28 days of trial treatment.

• Active autoimmune disease that has required systemic treatment in past 2 years

• Chronic usage of steroids or other immunosuppressant medication.

• Previous history of pneumonitis.

• Any evidence of clinical autoimmunity.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• pembrolizumab
anti PD-1

Locations

Country	Name	City	State
United Kingdom	University Hospital Birmingham NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	United Lincolnshire Hospitals NHS Trust	Lincoln
United Kingdom	Barts Health NHS Trust	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	University College London Hospitals	London
United Kingdom	Maidstone and Tunbridge Wells NHS Trust	Maidstone	Kent
United Kingdom	The Christie NHS Foundation Trust	Manchester	Greater Manchester
United Kingdom	Southampton University Hospitals NHS Trust	Southampton	Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Birmingham	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Middleton G, Brock K, Savage J, Mant R, Summers Y, Connibear J, Shah R, Ottensmeier C, Shaw P, Lee SM, Popat S, Barrie C, Barone G, Billingham L. Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phas — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity - Treatment Related Dose Delay or Treatment Discontinuation	Adverse events will be recorded in relation to each cycle of treatment and graded according to CTCAE criteria. The toxicity co-primary outcome measure for the trial is defined as the occurrence of a treatment-related dose delay or treatment discontinuation due to toxicity.	Through study completion, a maximum of 2 years and 6 months after end of treatment
Primary	Efficacy - Durable Clinical Benefit	Patients will have CT scans every 9 weeks from baseline until disease progression. On each occasion, overall tumour burden will be assessed using RECIST version 1.1. The efficacy co-primary outcome measure for the trial is durable clinical benefit defined as the occurrence of CR, PR or SD without prior progressive disease at or after the second scheduled CT scan (scheduled to occur at 18 weeks).	=18 weeks, up to maximum of 2 years
Secondary	Objective Response	Objective response (OR) is the occurrence of CR or PR as the best overall response. OR will be based on responses confirmed using the subsequent 9-weekly scan but OR based on unconfirmed responses will also be reported.	=18 weeks, up to maximum of 2 years
Secondary	Health Related Quality of Life	This is defined as the functional effect of a medical condition and/or its consequent treatment upon a patient. The purpose of Health Related Quality of Life (HRQoL) measurement is to quantify the degree to which the medical condition or its treatment impacts the individual's life in a valid and reproducible way. HRQoL will be assessed over time using FACT-L questionnaire and EQ-5D questionnaire.	Through study completion, up to a maximum of 2 years
Secondary	Time to Progression	This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded. Patients with no recorded progression at the time of analysis or who die without recorded progression will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.	Time to progression up to 2 years
Secondary	Progression-free Survival Time	This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression. Patients who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.	Progression-free survival time up to 2 years
Secondary	Overall Survival Time	This is defined as the time from commencement of trial treatment to the date of death. Patients who are alive at the time of analysis will be censored at the date last seen alive.	Survival time up to 2 years or date of death
Secondary	Duration of Objective Response and Duration of Stable Disease	This is defined as the time from commencement of trial treatment to the date of the subsequent CT scan when progressive disease is first confirmed or date of death without previously recorded progression. This outcome is calculated and reported separately for patients who achieve an OR or SD. Patients experiencing OR or SD who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.	Survival time up to 2 years or date of death