Parp Inhibitor in Advanced Non-Small Cell Lung Cancer (PIN)
- Registration Number
- NCT01788332
- Lead Sponsor
- Lisette Nixon
- Brief Summary
In 2010, more than 35,000 people died in the United Kingdom from lung cancer, the majority from non-small cell cancer (NSCLC). Chemotherapy is one of the main treatments for patients with NSCLC but those treated will still only live for an average of 9 or 10 months after diagnosis.
The purpose of this clinical trial is to find out whether or not giving a drug called Olaparib following chemotherapy will benefit patients with NSCLC who have responded to initial chemotherapy treatment by prolonging the time before the tumour regrows. Olaparib is a new, oral drug developed by AstraZeneca which may help to slow down cancer growth. The rationale for this clinical trial is that chemotherapy damages tumour cell DNA and NSCLC tumours that respond to chemotherapy are less able to repair this damage. This can be exploited by using Olaparib as it blocks an enzyme called Poly (ADP-ribose) polymerase (PARP) which is essential for DNA repair. This will prevent DNA repair and cause cancer cell death by a mechanism known as synthetic lethality. Synthetic lethality arises when a combination of mutation in two or more genes leads to cell death.
Up to 300 patients who are to receive standard chemotherapy treatment will be initially registered into the trial. Of these patients, 114 patients who have responded to chemotherapy will be randomly allocated to receive either Olaparib or an inactive dummy pill or placebo by mouth. The trial will assess whether Olaparib delays disease progression following standard chemotherapy treatment in patients. It will also show whether the side effects of adding Olaparib following standard treatment are acceptable.
- Detailed Description
This is a multicentre randomised phase II trial. Patients are initially registered either before or during induction chemotherapy, their response to which will be used to determine whether they are eligible for randomisation. All patients will be asked to consent to archival tissue collection for translational analysis and to provide a translational blood sample. The second consent will precede randomisation to one of two groups of maintenance therapy (olaparib or placebo) with 1:1 randomisation if they have had an objectively measured complete or partial response following standard chemotherapy.
Randomised patients will receive olaparib or placebo until disease progression. They will be monitored by CT scan every two cycles until disease progression, where they will be managed according to local practice. Follow up will be for a maximum of 12 months from the point of randomisation or until disease progression.
All randomised patients for whom we have a baseline translational blood sample will be asked to provide a follow up blood sample upon randomisation and again at radiological progression. Registered patients with progressive disease after the initial induction chemotherapy will be asked to provide a follow-up blood sample at the end of induction chemotherapy.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 70
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 3 100mg tablets to be administered twice a day with approximately 240ml of water. Olaparib Olaparib 3 100mg tablets to be administered twice a day with approximately 240ml of water.
- Primary Outcome Measures
Name Time Method Progression-free survival 72 weeks To establish the anti-tumour activity of Olaparib (measured by progression free survival),we will document the time from randomisation to any disease progression and/or death, defined according to strict RECIST (Response Evaluation Criteria in Solid Tumours) v1.1. Lesions will be compared to baseline measurements to assess progression.
- Secondary Outcome Measures
Name Time Method Objective response rate 72 weeks This will be assessed based on radiological disease progression defined according to RECIST (Response Evaluation Criteria in Solid Tumours) v1.1.
Overall survival 72 weeks This will be calculated from the time of randomisation to date of death or date last known to be alive.
Safety 72 weeks An Independent Data Monitoring Committee will convene and assess safety when 10 and 20 patients on each arm have completed trial treatment. If the trial is deemed safe to continue then safety will be assessed again approximately every six months. Toxicity data will be assessed along with serious adverse events.
Change in tumour volume reduction 27 weeks Change in tumour volume reduction from randomisation to 6 months
Tolerability 72 weeks This will be assessed in terms of the number of treatment reductions, delays and withdrawals.
Feasibility 72 weeks Patients will complete a diary card every day to document compliance. Feasibility of use will also be assessed in terms of number of treatment reductions, delays and withdrawals.
Trial Locations
- Locations (20)
Blackpool Victoria Hospital
🇬🇧Blackpool, United Kingdom
Queen's Hospital
🇬🇧Burton Upon Trent, United Kingdom
Derby Teaching Hospitals NHS Foundation Trust
🇬🇧Derby, United Kingdom
Withybush General Hospital
🇬🇧Haverfordwest, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Royal Preston Hospital
🇬🇧Preston, United Kingdom
Bradford Royal Infirmary
🇬🇧Bradford, United Kingdom
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
University Hospitals of North Midlands
🇬🇧Stoke-on-Trent, United Kingdom
Wrexham Maelor Hospital
🇬🇧Wrexham, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, United Kingdom
University Hospitals of Morecambe Bay
🇬🇧Lancashire, United Kingdom
St James University Hospital
🇬🇧Leeds, United Kingdom
The James Cook University Hospital
🇬🇧Middlesbrough, United Kingdom
Singleton Hospital
🇬🇧Swansea, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
🇬🇧Coventry, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom