Parp Inhibitor in Advanced Non-Small Cell Lung Cancer (PIN) — PIN  

Non-small Cell Lung Cancer Clinical Trial

Official title: A Randomised Phase II Trial of Olaparib Maintenance Versus Placebo Monotherapy in Patients With Chemosensitive Advanced Non-Small Cell Lung Cancer

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

• NCT number: NCT01788332
• Study type: Interventional
• Source: Velindre NHS Trust
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 2014
• Completion date: December 2018