A Phase 1 interventional study of acetazolamide in combination with platinum and etoposide-based radiochemotherapy and acetazolamide in combination with radioimmunotherapy in patients with extensive SCLC in Small Cell Lung Cancer, sponsored by Centre Antoine Lacassagne. Recruiting at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-20.
Sponsored by Centre Antoine Lacassagne · Phase 1, Interventional, and Treatment
The investigators propose to study the carbonic anhydrase inhibition (acetazolamide) associated with concomitant radiochemotherapy or radioimmunotherapy in small cell lung cancer due to:
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:
Exclusion Criteria:
Contraindication to thoracic radiotherapy treatment: congestive heart failure unbalanced (ejection fraction \<30%, clinical signs), severe respiratory failure:
non randomized, open-label extension cohort, evaluating the safety of acetazolamide in combination with platinum and etoposide-based radiochemotherapy in patients with Localized small lung cancer
Drug: acetazolamide in combination with platinum and etoposide-based radiochemotherapy
non randomized, open-label extension cohort, evaluating the safety of acetazolamide in combination with radioimmunotherapy in patients with extensive small cell lung cancer
Drug: acetazolamide in combination with radioimmunotherapy in patients with extensive SCLC
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).
acetazolamide in combination with radioimmunotherapy in patients with extensive SCLC
To identify the Tolerated Maximum Dose (DMT) and Recommended Dose (DR) of acetazolamide in combination with radiotherapy combined with platinum and etoposide chemotherapy (localized SCLC) or with radioimmunotherapy (extensive SCLC)
The frequency of limiting dose toxicities determined by the number of Adverse Events as Assessed by CTCAE v4.03 : * during the 6 weeks of treatment with acetazolamide / chemoradiation based on platinum and etoposide and in the first 6 months of follow-up after the last administration of the treatment * during the 10 days of treatment with acetazolamide / radioimmunotherapy and in the first 6 months after the last administration of the treatment with radioimmunotherapy, for the "extensive SCLC" subgroup
Time frame: 8 months
To determine the overall tolerance of the association acetazolamide and radiochemotherapy (localized SCLC) or of the association acetazolamide and radioimmunotherapy (extensive)SCLC)
The overall tolerability of the treatments will be measured by clinical (performance status), laboratory (blood sample), and paraclinical evaluations (ETT, EFR) and defined on the NCI CTCAE V4.03 scale
Time frame: 27 months
To evaluate the effectiveness of the treatment
The tumor response (complete or partial, stabilization, progression) will be performed by Morphological evaluations using a scanner according to RECIST 1.1 criteria
Time frame: 24 months
To evaluate the effectiveness of the treatment
The tumor response (complete or partial, stabilization, progression) will be performed by Metabolic evaluations using a PET-CT scan according to the criteria PERCIST 1.0
Time frame: 24 months
To identify predictive factors for response to acetazolamide
The evaluation of predictive factors of acetazolamide response will be determined by serum CAIX and CAXII levels (in the 7 days before the start of acetazolamide and the end-of-treatment visit)
Time frame: 3 months
To identify predictive factors for response to acetazolamide
The evaluation of predictive factors of acetazolamide response will be determined by: o The initial 18-FDG PET-CT scan (SUVmax, SULpeak) fixation intensity and 3 months after treatment,
Time frame: 30 months
To evaluate progression-free survival at 24 months
To determine the delay between the date of inclusion and the date of progression or death
Time frame: 24 months
To evaluate overall survival at 24 months
To determine the delay between the date of inclusion and the date of death
Time frame: 24 months
To determine the compliance of acetazolamide
Compliance assessment will be done using Girerd's questionnaire
Time frame: 27 months
To evaluate the quality of life
Quality of life will be determined using EORTC QLQC30 questionnaire
Time frame: 27 months
Plan to share: No
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Centre Antoine Lacassagne