Safety and effectiveness of doxycycline or placebo in adult participants with metastatic adenocarcinoma of the lung.

Start year: 2025

Summary: In people with cancer, concerns have been raised about the concomitant use of immune checkpoint inhibitors (ICI) and antibiotics leading to much poorer survival than people with no antibiotic exposure. By contrast, whole-of-cancer-population studies in New South Wales suggest that people receiving targeted (non-ICI) therapies for metastatic adenocarcinoma of the lung (n=3,815; 2013-2019) and antibiotics in the first six months after commencing systemic therapy have much better survival, especially if the antibiotics were tetracyclines. After controlling for other factors, the closer to the commencement of systemic therapy that antibiotics were prescribed, the greater benefit in survival. From these retrospective data, it is now necessary to confirm these findings with prospectively collected data. The multi-site, double-blind, placebo-controlled, parallel 2-arm, fixed dose, stratified, randomised Phase 2 study will evaluate initiating doxycycline 100mg daily for four weeks within five weeks of systemic therapy commencing in addition to standard care. Sixty participants with metastatic adenocarcinoma of the lung receiving first- or second line treatment with non-ICI systemic anti-cancer therapy will be enrolled; stratified by whether the participant had antibiotics in the six months before commencing systemic anti-cancer therapy. The primary outcome will be a win ratio hierarchical assessment at 12 months (death; response; ≥grade 4 toxicity; hospitalisations; delays to scheduled therapy). Win ratio analyses compare every dyadic combination (in this case 900 dyads) and assigns a ‘win’, ‘loss’ or ‘tie’ to each comparison. Where the event occurs in both members of the dyad, time to event will determine the outcome. This design allows for all outcomes to be compared with each dyad, ensuring that all data points are used.