Condition category
Cancer
Date applied
08/08/2016
Date assigned
11/08/2016
Last edited
24/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Dr Gillian McNab

ORCID ID

Contact details

Early Drug Development Team
Cancer Research UK Clinical Trials Unit (CRCTU)
Institute of Cancer and Genomic Sciences
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

2015-002241-55

ClinicalTrials.gov number

Protocol/serial number

31307

Study information

Scientific title

A phase II trial of pembrolizumab in patients with non-small cell lung cancer and a performance status of two

Acronym

Study hypothesis

The aim of this study is to:
1. Determine that pembrolizumab is safe and tolerable at the selected dose
2. Detect the response rate, disease control rate and durability of these in this population of patients treated with pembrolizumab

Ethics approval

West Midlands - Edgbaston Research Ethics Committee, 02/02/2016, ref: 16/WM/0010

Study design

Non-randomised; Interventional; Design type: Treatment, Screening, Diagnosis, Prevention, Drug, Imaging, Immunotherapy, Physical

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Lung; UKCRC code/ Disease: Cancer/ Malignant neoplasms of respiratory and intrathoracic organs

Intervention

Pembrolizumab will be administered to all participants as a 30 minute IV infusion, at a flat dose of 200 mg, at a dosing interval of every 3 weeks for a maximum of 2 years.

Follow up calls will be made every 4 weeks for 6 months then every 12 weeks to record treatment after progression and death date. Participants also undergo CT scanning every 9 weeks from baseline until disease progression, up to maximum of 2 years.

Intervention type

Drug

Phase

Phase II

Drug names

Pembrolizumab

Primary outcome measures

1. Toxicity is measured by recording adverse events in relation to each cycle of treatment and grading according to CTCAE criteria continuously from baseline to 6 months post-treatment
2. Response rate is measured using CT scanning every 9 weeks from baseline until disease progression, up to maximum of 2 years

Secondary outcome measures

1. Best objective response rate (ORR) is measured using CT scanning every 9 weeks from baseline until disease progression, up to maximum of 2 years
2. Health related quality of life is measured using FACT-L Quality of Life Questionnaire at each treatment cycle i.e. every 3 weeks until study completion (up to a maximum of 2 years)
3. Time to Progression (TTP), defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded, is measured through CT scanning every 9 weeks from baseline until disease progression, up to maximum of 2 years
4. Progression-free survival time (PFS), 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, is measured using RECIST 1.1 from baseline to up to maximum of 2 years
5. Overall survival time (OS), defined as the time from commencement of trial treatment to the date of death, is measured by patient survival until date of death
6. Duration of response (DoR), defined as the time from the CT scan when complete or partial response is first confirmed to the date of the subsequent CT scan when progressive disease is first confirmed or date of death without previously recorded progression, is calculated by RECIST 1.1 from baseline until disease progression, up to maximum of 2 years

Overall trial start date

01/12/2015

Overall trial end date

01/09/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients must have completed all standard of care therapy that the treating oncologist deems appropriate. All lines of therapy will be allowed
2. Histologically confirmed NSCLC where it is possible to assess PD-L1 status on tumour biopsy. Biopsy must be within 70 days of first treatment with pembrolizumab. All patients who have had systemic therapy since the biopsy must have a repeat biopsy that is evaluable for PD-L1.
3. Patients must have a performance status of 2 on the ECOG Performance scale with no deterioration over the previous 2 weeks assessed by consenting physician
4. Life expectancy >12 weeks
5. Uni-dimensionally measurable disease according to RECIST version 1.1
6. CT scan of chest and abdomen within 28 days of starting Pembrolizumab demonstrating measurable disease as per RECIST version 1.1
7. Demonstrate adequate haematological and organ function as defined below. All screening tests should be performed within 7 days of treatment
8. Age 18 years and over
9. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
10. Patients must agree to the use of contraception as detailed in protocol and patient information sheet
11. System laboratory values:
11.1. Haematological
Absolute neutrophil count ≥ 1.5 x 109/L
Haemoglobin ≥ 90 g/L or ≥5.6 mmol/L
Platelets ≥ 100 x 109/L
11.2. Hepatic function
Total serum bilirubin ≤ 1.5 x ULN
Alanine transferase (ALT) ≤ 2.5 x ULN.
Aspartate transferase (AST) ≤ 2.5 x ULN.
11.3. Renal function
Creatinine clearance <1.5 times ULN concurrent with creatinine clearance >50 ml/min (calculated by Cockcroft and Gault equation or alternative method). If this is ≤50 ml/min then an isotopic GFR may be undertaken and must be >50 ml/min.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 60; UK Sample Size: 60

Participant exclusion criteria

1. Untreated symptomatic brain or leptomeningeal metastatic disease
2. Medical or psychiatric conditions comprising informed consent
3. 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
4. Patient who has had chemotherapy, radioactive or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or who has not recovered to CTCAE grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks earlier. Patient who has had erlotinib, gefitinib, afatinib, or crizotinib within 1 week prior to the first dose of study therapy, or who has not recovered to CTCAE Grade 1 or better from the adverse events due to any of these drugs administered more than 1 week earlier. Patient who has had ipilimumab therapy may be enrolled if requirements specified in Inclusion Criterion are met.
5. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
7. Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess and abdominal carcinomatosis)
8. Patient has a known history of malignancy, unless the patient has undergone potentially curative therapy with no evidence of that disease for 5 years
9. Previous history of pneumonitis or significantly reduced transfer coefficient (KCO)
10. Female patients of child bearing potential should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing
11. Patient previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody
12. Patient had prior treatment targeting PD-1: PD-L1 axis or was previously randomized in any Pembrolizumab trial
13. Patient is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected); patients with negative Hepatitis C antibody testing may not need RNA testing
14. Known history of tuberculosis
15. Patient has an active infection requiring therapy
16. Has received a live vaccine within 30 days prior to the first dose of trial treatment
17. Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
18. Patients with symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible

Recruitment start date

30/09/2016

Recruitment end date

01/09/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University College London Hospital
1st Floor Central 250 Euston Road
London
NW1 2PG
United Kingdom

Trial participating centre

Southampton University Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Royal Marsden Hospital
Fulham Road
London
SW3 6JJ
United Kingdom

Trial participating centre

Barts Cancer Institute
Queen Mary University of London Old Anatomy Building Basement Room 2 Charterhouse Square
London
EC1M 6BQ
United Kingdom

Trial participating centre

Clatterbridge Cancer Centre
Clatterbridge Road
Wirral
CH63 4JY
United Kingdom

Trial participating centre

The Christie NHS Foundation Trust
550 Wilmslow Road Withington
Manchester
M20 4BX
United Kingdom

Trial participating centre

Maidstone Hospital
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom

Trial participating centre

Velindre Cancer Centre
Whitchurch
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

Western General Hospital
Crewe Road South
Edinburgh
EH 4 2XU
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Road
Newcastle upon Tyne
NE7 7DN
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Vincent Drive
Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Merck Sharp and Dohme

Alternative name(s)

Merck Sharp & Dohme, Merck Sharp & Dohme Corp., MSD

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

24/11/2016: Internal review.