NCT01562210

Olaparib Dose Escalating Trial + Concurrent RT With or Without Cisplatin in Locally Advanced NSCLC

Olaparib Dose Escalating Trial in Patients Treated With Radiotherapy With or Without Daily Dose Cisplatin for Locally Advanced Non-small Cell Lung Carcinoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase I dose escalating trial. Primary objective of this study is to define the maximal tolerated dose (MTD)of Olaparib in combination with high dose radiotherapy with or without daily dose Cisplatin in locally advanced NSCLC. Secondary objectives include to define safety profile, determine PK/Pd variables and document preliminary evidence of objective tumor response.

Detailed description

Concurrent chemoradiotherapy (CCRT) is the treatment of choice for patients with locally advanced NSCLC. The cure rates however need to be improved. The main mechanism by which both radiation and Cisplatin kill tumor cells is by an accumulation of un- or misrepaired DNA damage.PARP inhibitors increase radiation and chemotherapy (Cisplatin) response in preclinical studies including lung cancer models. This open label dose escalating trial consists of a screening phase, a treatment phase and a follow up phase. The screening phase: patients who can tolerate concurrent cisplatin will receive Olaparib, RT and Cisplatin. Patients who can not tolerate concurrent cisplatin will receive Olaparib and RT with or without prior sequential chemotherapy. The treatment phase:dose escalation of Olaparib will be performed in cohorts of 3 subjects. The decision to escalate to the next dose level will be based on the occurrence of DLTs during the DLT evaluation period (i.e. 3 months following the last day of irradiation) and will be made after all patients within the cohort have completed their third month of follow up. Active follow-up phase: frequent follow up will take place during the first 3 months (acute toxicity). Thereafter patients will be monitored for late toxicity and for disease activity 3-monthly throughout the first year and thereafter 6-monthly until 5 years, when patients are deemed to be cured and follow up is no longer warranted. Olaparib will be given orally BID for 36 consecutive days, administrated with a 12 hour interval. Olaparib will start 2 days before start of RT and will continue for 2 days after the last RT fraction. Olaparib is also given during the non-radiotherapy days but no maintenance treatment is given after radiotherapy is finished. Radiotherapy (for all patients): a total dose of 66Gy will be given in 24 fractions from week 1 to 5. Cisplatin (concurrent chemoradiotherapy): daily dose Cisplatin 6mg/m2 (5 days/week), 1-1.5 hr before the irradiation (week 1 to 5), given as a 5-minutes intravenous infusion.

Conditions

• NSCLC

Interventions

Type	Name	Description
DRUG	Olaparib	Olaparib will be given orally BID for 36 days, administrated with a 12 hour interval. Olaparib will start 2 days before RT and will continue for 2 days after the last RT fraction. Olaparib is also given during the non-radiotherapy days but no maintenance treatment is given after radiotherapy is finished. The first cohort will receive Olaparib with a dose of 25mg BID combined with Cisplatin and RT. Thereafter in both with and without cisplatin arms dose escalation will follow to 50mg, 100mg, 200mg, 300mg and 400mg BID.
DRUG	Cisplatin	6 mg/m2 (5 days/week), 1-1.5 hr before the irradiation (week 1 to 5), given as a 5-minutes intravenous infusion.
RADIATION	Radiation	A total dose of 66 Gy will be given in 24 fractions from week 1 to 5, excluding the weekends.

Timeline

• Start date: 2012-04-01
• Primary completion: 2019-05-01
• Completion: 2020-03-13
• First posted: 2012-03-23
• Last updated: 2020-03-17

Locations

1 site across 1 country: Netherlands