Trial Evaluating Maintenance Olaparib in Patients With Platinum-sensitive Advanced Non-small Cell Lung Cancer
Summary
This is a multicentre randomised double-blind phase II trial, sponsored by Gustave Roussy and involving one French center as well as the Spanish Lung Cancer Group (≈20 centers of the SLCG). Six hundred patients with diagnosis of stage IIIB/IV NSCLC will initially be registered prior to receiving the first line platinum-based chemotherapy or during or at the end of the first 6 cycles of inducation platinium based chemotherapy and provide consent for retrieving archival tissue collection and providing translational blood samples and tumor biopsies. 1. \- Induction chemotherapy phase All patients will initially be treated with 6 cycles of platinum-based induction chemotherapy. Cycle duration will be 21 days. Doublets should either consist of a pemetrexed-platinum (cisplatin or carboplatin) doublet (preferentially for non-squamous NSCLC) or a gemcitabine - or vinorelbine - platinum doublet for squamous NSCLC. Taxanes-platinum doublets will not be accepted. Translational blood samples will be taken at the beginning of induction chemotherapy for all patients. Patients displaying progressive disease or stable disease after induction chemotherapy will be withdrawn and further optimally managed according to local practice. For them, an optional tumour biopsy will be performed at the end of the induction treatment. 2. \- Randomisation and maintenance phase Only patients who respond to platinum-based induction chemotherapy will be further randomised between olaparib and placebo. These patients must have been treated with 6 cycles of chemotherapy. However, patients who haven't received 6 cycles of the induction chemotherapy due to severe toxicity (grade 3 or 4, NCI CTCAE v4.0) could be randomized only if they had received 4 chemotherapy cycles at least and if all treatment related toxicities are resolved to a grade ≤ 1 (NCI CTCAE v4.0). Treatment will be administered at a dose of 600 mg daily (2 doses of 300 mg \[2 tablets of 150 mg\] taken approximately 12 hours apart) and cycle duration will be 28 days. Disease will be assessed every 2 cycles by CTscan (MRI or PET-scan if the scan is not contributive) and treatment will be administered until disease progression or unacceptable toxicity. Patients will then be optimally managed according to local practice. Follow-up will be for a minimum of 15 months from the time of randomization, and until last venue. All randomised patients will be asked to provide translational blood samples at randomization, on treatment and at the end of the treatment. Optional tumour biopsies will be performed at randomization, at the end of the treatment (or at disease progression if available).
Timeline
- Start
- 2016-02-05
- Primary completion
- 2020-12-22
- Completion
- 2022-03-25
Outcome
Missed primary endpoint
Stopped (Enrollment): “study design, change of standard of care, enrollment difficulties”
paper The median PFS was 2.9 and 2.0 months in the O and P arms, respectively (logrank p = 0.99). PMID 38097741 ↗
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Olaparib | Small molecule | 600 mg | Oral |