Clinical trial NCT02733159: Pembrolizumab in Patients With Non-Small Cell Lung Cancer and a Performance Status 2
Official title: A Phase II Trial of Pembrolizumab in Patients With Non-small Cell Lung Cancer and a Performance Status of 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Performance Status 2
Pembrolizumab
MK-3475
Lead sponsor: University of Birmingham
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-04-11
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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 (PS) 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.

Eligibility criteria: Core Inclusion Criteria:

* Histologically confirmed PD-L1 status defined NSCLC. Biopsy must be within 70 days of first treatment with pembrolizumab.
* Eastern Cooperative Oncology Group (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.

Primary outcomes:
measure: Toxicity Rate
timeFrame: Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment)
measure: Durable Clinical Benefit
timeFrame: ≥18 weeks, up to maximum of 2 years
Secondary outcomes:
measure: Objective Response
timeFrame: ≥18 weeks, up to maximum of 2 years
measure: Health Related Quality of Life
timeFrame: Through study completion, up to a maximum of 2 years
measure: Time to Progression
timeFrame: Time to progression up to 2 years
measure: Progression-free Survival Time
timeFrame: Progression-free survival time up to 2 years
measure: Overall Survival Time
timeFrame: Survival time up to 2 years or date of death
measure: Duration of Objective Response
timeFrame: Survival time up to 2 years or date of death
measure: Duration of Stable Disease
timeFrame: Survival time up to 2 years or date of death
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
state: Hampshire
city: Maidstone
country: United Kingdom
facility: Maidstone and Tunbridge Wells NHS Trust
state: Kent
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Foundation Trust
state: West Midlands
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Lincoln
country: United Kingdom
facility: United Lincolnshire Hospitals NHS Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: University of Birmingham
name: Gary Middleton, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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, phase 2 trial. Lancet Respir Med. 2020 Sep;8(9):895-904. doi: 10.1016/S2213-2600(20)30033-3. Epub 2020 Mar 19.