NCT04550104

A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC

A Platform Study of DNA Damage Response Inhibitors in Combination With Conventional Radiotherapy in Non Small Cell Lung Cancer

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 200 (estimated)
• Sponsor: University of Leeds · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

CONCORDE is a multi-institution, multi-arm, Phase IB study that will determine the recommended phase II dose (RP2D) and safety profiles of different DNA damage repair inhibitors (DDRis) when given in an open label fashion in combination with fixed dose curative intent radiotherapy (RT) in patients with stage IIB/IIIA/IIIB NSCLC, followed by up to 12 months of consolidation durvalumab immunotherapy in selected study arms. The RP2D will be evaluated by incorporating the number of observed dose limiting toxicities (DLTs) into a time to event continuous reassessment method (TiTE- CRM) model within each of the experimental arms. TiTE-CRM is used here to take into account longer-term toxicities up to 13.5 months post start of radiotherapy and use these to inform dose escalation decision making.

Detailed description

Radiotherapy is an effective treatment for patients with non-small cell lung cancer (NSCLC) that has not spread beyond the chest area. Radiotherapy is used as a curative treatment but unfortunately for most patients the cancer can return. Radiotherapy kills cells by damaging their DNA. Cells have the ability to repair that damage, especially the cells of normal tissue. If DNA repair can be prevented radiotherapy should be more effective causing the cancer cells to die. The study will use new drugs that affect how cells repair DNA damage, called DNA damage response inhibitors (DDRi). These will be given together with radiotherapy to hopefully improve the effectiveness of radiotherapy, followed by up to 12 months of durvalumab immunotherapy in selected study arms to develop the trial in line with the standard of care for NSCLC. The study will try to find out the most effective and safe dose of this combination treatment. This will be a clinical trial where patients due to have radiotherapy, with the hope of successful treatment that could lead to cure from their cancer or extension of life, will be offered entry onto the study. All patients will receive their radiotherapy, with 3 out of every 4 people also receiving a single DDRi drug alongside this. Both patients and study doctors will know prior to the start of the actual treatment whether a DDRi will be given, and if so which one; no placebos will be used. The patients will be followed closely to check for side effects and to assess how their cancer is responding to treatment. Blood samples will be taken to monitor treatment progress and to try to predict which patients are most likely to benefit from this type of combined treatment.

Conditions

• Non Small Cell Lung Cancer

Interventions

Type	Name	Description
RADIATION	Radiotherapy	Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
DRUG	Olaparib Oral Tablet [Lynparza]	Oral tablet
DRUG	AZD1390	Oral tablet
DRUG	Ceralasertib	Oral Tablet
DRUG	AZD5305	Oral Tablet
DRUG	Durvalumab	1500mg iv infusion

Timeline

• Start date: 2021-03-17
• Primary completion: 2026-03-01
• Completion: 2028-03-01
• First posted: 2020-09-16
• Last updated: 2025-12-19

Locations

14 sites across 1 country: United Kingdom