Combining acetazolamide with chemotherapy and radiotherapy for small cell lung cancer

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

This study is testing if adding acetazolamide to chemotherapy and radiotherapy can help people with small cell lung cancer get better results from their treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Antoine Lacassagne (Academic / other)
• Drugs / interventions: atezolizumab, durvalumab, chemotherapy, immunotherapy
• Locations: 2 sites (Nice and 1 other locations)
• Trial ID: NCT03467360 on ClinicalTrials.gov

What this trial studies

This study investigates the use of acetazolamide, a carbonic anhydrase inhibitor, in combination with radiochemotherapy or radioimmunotherapy for patients with small cell lung cancer (SCLC). The approach is based on the over-expression of carbonic anhydrases in SCLC and the potential anti-tumor effects observed in preclinical studies. By targeting glucose metabolism and manipulating the tumor microenvironment, the study aims to enhance the effectiveness of standard treatments. This is the first clinical evaluation of acetazolamide in oncology, particularly in conjunction with radiotherapy and chemotherapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with localized or extensive small cell lung cancer who are about to start or have recently received specific chemotherapy and immunotherapy regimens.

Not a fit: Patients with metastatic small cell lung cancer or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with small cell lung cancer by enhancing the effectiveness of existing therapies.

How similar studies have performed: While this specific combination has not been tested in humans before, preclinical studies have shown promising results with similar approaches.

Eligibility criteria

Inclusion Criteria:

* Age \> or = 18 years,
* Performance Status 0 to 2,
* Patient with an histologically non-metastatic localized (or extensive SCLC sub-group) Small cell lung cancer,
* Patient who must start radiotherapy treatment combined with chemotherapy with platinum and etoposide (localized SCLC sub-group) or Patient who received 4 cycles of chemoimmunotherapy with platinum salts, etoposide and immunotherapy (atezolizumab or durvalumab) as the first treatment (extensive SCLC sub-group) 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, renal or adrenal insufficiency, sulfonamide intolerance, history of renal colic, allergy to wheat other than celiac disease,
* Patient currently receiving one or more treatments described in section 6.9 of the protocol,
* 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,
* 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

Where this trial is running

Nice and 1 other locations

• Centre Antoine Lacassagne — Nice, France (Recruiting)
• Centre Hospitalier Princesse grace — Monte Carlo, Monaco (Terminated)

Study contacts

• Study coordinator: Jérôme DOYEN, PH

Conditions Small Cell Lung Cancer; acetazolamide