Combination of 3 repurposed drugs after chemotherapy failure in lung cancer
A prospective phase II, randomised multi-center trial of a biomodulatory treatment with metronomic low-dose treosulfan, pioglitazone and clarithromycin versus nivolumab in patients with squamous cell lung cancer and non-squamous cell lung cancer, respectively, after platin failure (ModuLung).
- Lung cancer
Why this trial?
Lung cancer is the most common cancer type worldwide and the most common cause of death from cancer. Non-small cell lung cancer (NSCLC) is the main type of lung cancer, accounting for approximately 85% of all lung cancer cases. Approximately 15% of patients survive for at least 5 years after being diagnosed with NSCLC.
In cases where the tumour is small or confined to only one lung, it can be cured by surgery or radiotherapy. Unfortunately, at the time of diagnosis, NSCLCs are often too large, or have spread to other parts of the body. In this case, standard treatment consists of platinum-based chemotherapy. If this first chemotherapy treatment fails, the next option is the recently approved nivolumab.
Scientific data suggest that it is important to act on several aspects of the tumour to achieve a long-term benefit. Preventing the formation of blood vessels that are needed for tumour growth, modulating the inflammatory and immune environment of the tumour, and changing tumour cell behaviour may be more effective, provide a survival benefit, as well as improve the quality of life in patients with advanced cancers.
This study will compare the standard treatment with nivolumab to the experimental treatment, which consists of a combination of 3 oral drugs that are currently on the market for other indications than lung cancer. These drugs could be potentially useful in the treatment of NSCLC because they have shown an effect on both the tumour environment and the tumour cells.
Why this drug?
Clarithromycin is an antibiotic that affects inflammation. In a small trial completed in Japan, NSCLC patients who received clarithromycin showed prolonged survival compared to the group that received standard treatment. In addition, there is evidence that clarithromycin controls tumour-associated inflammation and improves cachexia (a condition in which the patient loses weight and muscle tissue and is weak and tired).
Pioglitazone, currently on the market to treat diabetes, affects the growth of (tumour) cells and cell death.
Treosulfan is a chemotherapeutic drug which will be used at a “metronomic dose”, i.e. at a lower but more frequent dose than the usual schedule.
This is a prospective phase II, randomised trial in 10 German centres. Of 86 NSCLC patients, half will receive the experimental treatment with treosulfan, pioglitazone and clarithromycin and the other half will receive nivolumab.
The main objective is to compare the efficacy of the experimental therapy to the efficacy of nivolumab in this specific patient population. Safety and quality of life will also be evaluated.
- Prof. A. Reichle, University Hospital Regensburg, Regensburg, Germany (Coordinating Investigator)
- Prof. C. Schulz, University Hospital Regensburg, Regensburg, Germany
- University Hospital Regensburg, Regensburg, Germany
More info on clinicaltrials.gov: NCT02852083
Mikasa, K., et al. (1997). Significant Survival Benefit to Patients with Advanced Non-Small-Cell Lung Cancer from Treatment with Clarithromycin. Chemotherapy, 43, 288-296. doi:10.1159/000239580
Kazandjian, D., et al. (2016). FDA Approval Summary: Nivolumab for the Treatment of Metastatic Non-Small Cell Lung Cancer With Progression On or After Platinum-Based Chemotherapy. The Oncologist, 21(5), 634-42. doi: 10.1634/theoncologist.2015-0507
NSCLC Meta-Analyses Collaborative Group. (2008). Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. Journal of clinical oncology, 26(28), 4617-25. doi: 10.1200/JCO.2008.17.7162
Reichle, A. (2013). Evolution-adjusted tumor pathophysiology. Springer. doi:10.1007/978-94-007-6866-6
Reichle, A. (2010). From Molecular to Modular Tumor Therapy: Tumors are Reconstructible Communicatively Evolving Systems. Springer. doi:10.1007/978-90-481-9531-2
Author: Kristine Beckers (Trial Manager)
Last updated: June 2018.