NCT03467360

Phase I Trial of CArbonic Anhydrase Inhibition in Combination With Radiochemotherapy or Radioimmunotherapy in Small Cell Lung Carcinoma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Centre Antoine Lacassagne · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The investigators propose to study the carbonic anhydrase inhibition (acetazolamide) associated with concomitant radiochemotherapy or radioimmunotherapy in small cell lung cancer due to: 1. The over-expression of carbonic anhydrases in this type of cancer, 2. The Anti-tumor effect in preclinical acetazolamide in various tumor lines including neuroendocrine tumor lines, 3. The observed synergy between irradiation and inhibition of carbonic anhydrases, 4. Potential anti-tumor immune effect caused by decreased extracellular acidity.

Detailed description

Compared with healthy cells, glucose metabolism is greatly modified in cancer cells because of their highly proliferative character. This differential tumor / healthy tissue property is an opportunity to be able to propose a treatment whose therapeutic gain can be major (targeted treatment). Preclinical studies are multiple and showed that the targeting of overexpressed proteins (carbonic anhydrases) and involved in glycolytic metabolism can lead to a significant anti-tumor effect. This has never been tested in humans. Acetazolamide is a molecule commonly used for non carcinologic purposes but has demonstrated anti-tumor activity in preclinical studies; there is also synergy radiotherapy / targeting of carbonic anhydrases. Therefore, the investigators propose to study the combination of acetazolamide / radiotherapy / chemotherapy with platinum and etoposide in localized Small Cell Lung cancer, or associated with radioimmunotherapy (extensive SCLC). This would be the first study: * targeting glucose metabolism, * testing the effectiveness of acetazolamide in oncology, * testing the synergy radiotherapy / targeting glycolytic metabolism, * trying to manipulate the anti-tumor immune system indirectly, by decreasing extracellular acidosis.

Conditions

• Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	acetazolamide in combination with platinum and etoposide-based radiochemotherapy	Radiation therapy will be combined with platinum and etoposide-based chemotherapy combined with 3-6 tablets per day of acetazolamide during the entire course of therapy (dosage appropriate to the inclusion phase).
DRUG	acetazolamide in combination with radioimmunotherapy in patients with extensive SCLC	acetazolamide in combination with radioimmunotherapy in patients with extensive SCLC

Timeline

• Start date: 2019-08-02
• Primary completion: 2026-10-27
• Completion: 2027-04-27
• First posted: 2018-03-16
• Last updated: 2026-01-20

Locations

2 sites across 2 countries: France, Monaco