Parp Inhibitor in Advanced Non-Small Cell Lung Cancer (PIN)
PIN
A Randomised Phase II Trial of Olaparib Maintenance Versus Placebo Monotherapy in Patients With Chemosensitive Advanced Non-Small Cell Lung Cancer
1 other identifier
interventional
70
1 country
20
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 nonsmall-cell-lung-cancer
Started Jan 2014
Typical duration for phase_2 nonsmall-cell-lung-cancer
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 4, 2013
CompletedFirst Posted
Study publicly available on registry
February 11, 2013
CompletedStudy Start
First participant enrolled
January 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2018
CompletedOctober 26, 2018
October 1, 2018
4.9 years
February 4, 2013
October 24, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival
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.
72 weeks
Secondary Outcomes (6)
Safety
72 weeks
Objective response rate
72 weeks
Overall survival
72 weeks
Change in tumour volume reduction
27 weeks
Tolerability
72 weeks
- +1 more secondary outcomes
Study Arms (2)
Olaparib
ACTIVE COMPARATOR3 100mg tablets to be administered twice a day with approximately 240ml of water.
Placebo
PLACEBO COMPARATOR3 100mg tablets to be administered twice a day with approximately 240ml of water.
Interventions
Olaparib is a potent inhibitor of poly (ADP-ribose) polymerase enzyme (PARP), (molecular weight 434) that is being developed as a monotherapy as well as for combination with chemotherapy and other anti-cancer agents. Olaparib can lead to tumour regression in patients with DNA repair deficient NSCLC. Olaparib may also enhance the DNA damaging effects of chemotherapy.
Eligibility Criteria
You may qualify if:
- Histological diagnosis of NSCLC. Histology can be either squamous or non-squamous.
- Stage IIIB or stage IV lung cancer that is not amenable to curative therapy.
- Have had no prior systemic chemotherapy for advanced NSCLC. Previous adjuvant or neoadjuvant chemotherapy for non-advanced disease is acceptable. Prior treatment with an oral targeted therapy for e.g. EGFR/ALK or other driver- oncogene mutated lung cancer is allowed. Immunotherapy e.g. with a PD1 or PDL1 targeted agent is allowed.
- Patients who have already started their induction chemotherapy are not eligible for stage 1 of the trial
- Eligible to receive standard platinum doublet-based chemotherapy.
- Men or women, aged 18 or over and capable of giving informed consent.
- Willing to consent to provide tissue and blood for translational research.
- Informed consent prior to any study specific procedures.
You may not qualify if:
- Evidence of small cell, large cell neuroendocrine or carcinoid histology.
- Have a serious or uncontrolled medical condition that could compromise the patients' ability to adhere to the protocol.
- Have a secondary malignancy (except adequately treated non-melanomatous skin cancer, or other cancer considered cured by surgical resection or radiation). Patients who have had another malignancy in the past but have been disease free for more than 5 years are eligible.
- Previous treatment with PARP inhibitors
- Uncontrolled gastrointestinal disorders such as active diverticulitis or colitis, or any major GI resection which could have an impact on patients' ability to absorb Olaparib.
- Myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML).
- Confirmed diagnosis of NSCLC (either squamous or non-squamous). Stage IIIB or stage IV that is not amenable to curative therapy.
- ECOG performance status 0-1
- Evidence of radiological response to induction chemotherapy, from the pre-treatment to baseline. This can include mixed stable/response or evidence of tumour shrinkage that does not reach the criteria of partial response according to RECIST.
- Have had no prior systemic chemotherapy for advanced NSCLC. Previous adjuvant or neoadjuvant chemotherapy for non-advanced disease is acceptable. Previous palliative radiotherapy to non-target metastases is allowed provided no more than 25% of the bone marrow volume is irradiated. Irradiated sites cannot include the sites of measurable disease unless clear tumour progression has been documented in them since the end of radiation therapy. Patients who have had adjuvant therapy and then progressed after a year of completing adjuvant therapy are eligible. Patients who have received an oral inhibitor for molecularly stratified subgroups e.g. EGFR or ALK mutated lung cancer, are allowed. Immunotherapy e.g. with a PD1 or PDL1 targeted agent is allowed.
- Adequate organ function, including the following:
- Adequate bone marrow reserve: White cell count ≥ 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, haemoglobin ≥ 90g/L.
- Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) ≤ 2.5 x ULN. ALP, AST, and ALT ≤ 5 x ULN is acceptable if the liver has tumour involvement.
- Renal: calculated creatinine clearance (CrCl) ≥ 50mL/min using Cockcroft-Gault or Wright formula, serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN).
- If blood count/morphology suggestive of MDS/AML, no features suggestive of MDS/AML on peripheral blood smear.
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Lisette Nixonlead
- AstraZenecacollaborator
Study Sites (20)
Blackpool Victoria Hospital
Blackpool, United Kingdom
Bradford Royal Infirmary
Bradford, United Kingdom
Queen's Hospital
Burton-on-Trent, United Kingdom
Velindre Cancer Centre
Cardiff, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, United Kingdom
Derby Teaching Hospitals NHS Foundation Trust
Derby, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Withybush General Hospital
Haverfordwest, United Kingdom
Huddersfield Royal Infirmary
Huddersfield, United Kingdom
University Hospitals of Morecambe Bay
Lancashire, United Kingdom
St James University Hospital
Leeds, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Charing Cross Hospital
London, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
The James Cook University Hospital
Middlesbrough, United Kingdom
Royal Preston Hospital
Preston, United Kingdom
Weston Park Hospital
Sheffield, United Kingdom
University Hospitals of North Midlands
Stoke-on-Trent, United Kingdom
Singleton Hospital
Swansea, United Kingdom
Wrexham Maelor Hospital
Wrexham, United Kingdom
Related Publications (1)
Fennell DA, Porter C, Lester J, Danson S, Blackhall F, Nicolson M, Nixon L, Gardner G, White A, Griffiths G, Casbard A. Olaparib maintenance versus placebo monotherapy in patients with advanced non-small cell lung cancer (PIN): A multicentre, randomised, controlled, phase 2 trial. EClinicalMedicine. 2022 Aug 11;52:101595. doi: 10.1016/j.eclinm.2022.101595. eCollection 2022 Oct.
PMID: 35990583DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Dean Fennell, Professor
University of Leicester
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER GOV
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Senior Trial Manager
Study Record Dates
First Submitted
February 4, 2013
First Posted
February 11, 2013
Study Start
January 1, 2014
Primary Completion
December 1, 2018
Study Completion
December 1, 2018
Last Updated
October 26, 2018
Record last verified: 2018-10