MODULUNG: a prospective phase II, randomized multi-center trial of a biomodulatory treatment with 3 oral drugs versus docetaxel or docetaxel plus nintedanib in patients with non-small cell lung cancer after platin failure.

Info

Location: University Regensburg (Freistaat Bayern), Germany
Collaboration: Prof. Dr. A. Reichle, Prof. Dr. C. Schulz

 

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 cancers, accounting for approximately 85% of all lung cancer cases. In general, approximately 15% of patients survives for at least 5 years after being diagnosed with NSCLC.

When the lung tumor 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, have spread to other parts of the chest, or have spread to distant organs. In these cases, standard treatment consists of platinum-based chemotherapy. If this first chemotherapy treatment fails, the next option is the recently approved Nivolumab. About 2 patients in 10 will have their tumor shrunk thanks to Nivolumab and 2 to 3 other will have their disease stabilized.

Scientific data suggest that it is important to act on several aspects of the tumor to achieve a long term benefit. Preventing the formation of blood vessels that are needed by the tumor to grow, modulating the inflammatory and immune environment of the tumor as well as modifying the behavior of the tumor cells themselves may actually be even more effective, providing a survival benefit, as well as an improvement in the quality of life in patients with advanced cancers.

Therefore, this randomized study, where patients are randomly assigned to the experimental treatment group and control group, will compare the standard treatment with Nivolumab to the experimental treatment with a combination of 3 drugs that are currently on the market for other indications than lung cancer.
The experimental treatment consists of a combination of clarithromycin, pioglitazone and treosulfan. For these three drugs, there is already some scientific evidence that they can prevent the tumor to grow and survive.

The trial has been approved by the Ethics Committee and the Competent Authorities of Germany. This trial is set up in 9 hospitals in Germany and will include 86 patients in total. 21 patients have been enrolled in the trial (February 2017).

More details about this study (NCT02852083) at www.clinicaltrials.gov.

Professional info

Location: University Regensburg (Freistaat Bayern), Germany
Collaboration: Prof. Dr. A. Reichle, Prof. Dr. C. Schulz

 

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 cancers, accounting for approximately 85% of all lung cancer cases. In general, approximately 15% of patients survives for at least 5 years after being diagnosed with NSCLC.

When the lung tumor is small or confined to only one lung it can be cured by surgery or radiotherapy. Unfortunately, NSCLCs are often “locally advanced” when they are large or have spread to other parts in the chest, or “metastatic” when they have spread to distant organs. Standard treatment for locally advanced and metastatic NSCLC consists of platinum-based chemotherapy. If this first chemotherapy treatment fails, the next option is the recently approved Nivolumab (an anti-PD-1 monoclonal antibody). The objective response rate with nivolumab is about 20% with 25-30% of patients also experiencing disease stabilization. One year survival is between 42% and 51% depending on the subtype of NSCLC.

Whilst Nivolumab has given better results than docetaxel (former standard second line), it acts on one specific component of the tumor microenvironment. Scientific data suggest that it might be efficient to act on several aspects of the tumor to achieve a long-term benefit. Combining anti-angiogenesis, anti-inflammation, immune modulation and transcriptional modulation of tumor cells may actually be even more effective, both possibly providing a survival benefit and improving the quality of life in patients with advanced cancers.

Therefore, this randomized study, where patients are randomly divided over the treatment group and control group, will compare the standard treatment with Nivolumab to the experimental treatment with a combination of 3 oral drugs that are currently on the market for other indications than lung cancer. These drugs could potentially be useful in the treatment of NSCLC because they have shown an effect on both the tumor environment and the tumor cells.

The experimental treatment consists of a combination of clarithromycin, pioglitazone and treosulfan:

  • Clarithromycin is an antibiotic which has an effect on inflammation. In a small trial done in Japan, patients who received clarithromycin for NSCLC had their survival prolonged compared to the control group of patients receiving standard treatment. In addition, there is evidence that clarithromycin controls tumor-associated inflammation and improves cachexia, or condition in which the patient loses weight and muscle tissue and is weak and tired.
  • Pioglitazone, currently on the market to treat diabetes, has an effect on the growth of cells as well as 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.

The trial has been approved by the Ethics Committee and the Competent Authorities of Germany. This trial is set up in 9 hospitals in Germany and will include 86 patients in total to compare the efficacy of the experimental treatment to the efficacy of nivolumab. Additionally, the side effects (safety) and quality of life are verified. 21 patients have been enrolled (February 2017).

More details about this study (NCT02852083) at www.clinicaltrials.gov.