A Randomised Phase II Trial of Olaparib Maintenance Versus Placebo Monotherapy in Patients With Chemosensitive Advanced Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Olaparib
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Lisette Nixon
- Enrollment
- 70
- Locations
- 20
- Primary Endpoint
- Progression-free survival
- Last Updated
- 7 years ago
Overview
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.
Investigators
Lisette Nixon
Senior Trial Manager
Velindre NHS Trust
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Olaparib
3 100mg tablets to be administered twice a day with approximately 240ml of water.
Intervention: Olaparib
Placebo
3 100mg tablets to be administered twice a day with approximately 240ml of water.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: 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 Outcomes
- Objective response rate(72 weeks)
- Overall survival(72 weeks)
- Safety(72 weeks)
- Change in tumour volume reduction(27 weeks)
- Tolerability(72 weeks)
- Feasibility(72 weeks)