Inhibition of CArbonic Anhydrase in Combination With Platinum and Etoposide-based Radiochemotherapy in Patients With Localized Small Cell Lung Cancer (ICAR)

  • End date
    Nov 30, 2024
  • participants needed
  • sponsor
    Centre Antoine Lacassagne
Updated on 25 March 2022
cancer chemotherapy
neuroendocrine tumor


The investigators propose to study the carbonic anhydrase inhibition (acetazolamide) associated with concomitant radiochemotherapy in localized 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.


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.

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.

Condition Small Cell Lung Cancer
Treatment acetazolamide in combination with platinum and etoposide-based radiochemotherapy
Clinical Study IdentifierNCT03467360
SponsorCentre Antoine Lacassagne
Last Modified on25 March 2022


Yes No Not Sure

Inclusion Criteria

Age > or = 18 years
Performance Status 0 to 2
Patient with an histologically non-metastatic localized Small cell lung cancer
Patient who must start radiotherapy treatment combined with chemotherapy with platinum and etoposide, Note: The decision of the Multidisciplinary Consultation Team must be notified in the patient's medical file
Evaluation lesion according to the criteria RECIST 1.1 and / or according to the criteria PERCIST 1.0
Women of childbearing potential must have a negative serum pregnancy test within 72 hours of the first administration of the study treatment
If the patient is a woman of childbearing potential, she must be surgically sterile or agree to use two adequate methods of contraception throughout the duration of the study until 1 month after the last administration of the study treatment. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year, Note: Abstinence is acceptable if it is the patient's usual and preferred form of contraception
If the male patient has one or more female partners of childbearing age, he / she must agree to use an adequate method of contraception, starting at the first administration of the study treatment up to 1 month after the last administration of the treatment. of the study, Note: Abstinence is acceptable if it is the patient's usual and preferred form of contraception
Patient willing and able to provide written informed consent/assent for the trial
Patient affiliated with a health insurance system

Exclusion Criteria

Patient with metastatic disease
History of thoracic irradiation or near / in the thoracic irradiation field
Patient who refuses to participate in the study or unable to agree
Contraindication to thoracic radiotherapy treatment: congestive heart failure unbalanced (ejection fraction <30%, clinical signs), severe respiratory failure
COPD grade IV according to the GOLD classification
Some GOLD III COPD and any patient with a respiratory defect defined as: oxygen dependence and / or FEV1 <40% normal and / or, DLCO <40% predictive value and / or vital capacity <40% predictive value
Contraindication to acetazolamide: hypersensitivity to acetazolamide, severe hepatic
Patient currently receiving one or more treatments described in section 6.9 of the protocol
renal or adrenal insufficiency, sulfonamide intolerance, history of renal
History of cancer, with the exception of cancers in complete remission for more than 5 years, completely resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
colic, allergy to wheat other than celiac disease
People particularly vulnerable as defined in Articles L.1121-5 to -8 of the French Healthcare Code, including: person deprived of freedom by an administrative or judicial decision, adult being the object of a legal protection measure or outside a state to express their consent, pregnant or breastfeeding women
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