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

NCT03467360 | Recruiting Phase 1 DMC

• 3 other identifiers: 2017/142022-503093-36-002017-002160-40
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 2

Brief 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. 1.The over-expression of carbonic anhydrases in this type of cancer,
2. 2.The Anti-tumor effect in preclinical acetazolamide in various tumor lines including neuroendocrine tumor lines,
3. 3.The observed synergy between irradiation and inhibition of carbonic anhydrases,
4. 4.Potential anti-tumor immune effect caused by decreased extracellular acidity.

Conditions

Small Cell Lung Cancer

Keywords

acetazolamide

Outcome Measures

Primary Outcomes (1)

• 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

  8 months

Secondary Outcomes (9)

• To determine the overall tolerance of the association acetazolamide and radiochemotherapy (localized SCLC) or of the association acetazolamide and radioimmunotherapy (extensive)SCLC)

  27 months

• To evaluate the effectiveness of the treatment

  24 months

• To evaluate the effectiveness of the treatment

  24 months

• To identify predictive factors for response to acetazolamide

  3 months

• To identify predictive factors for response to acetazolamide

  30 months

Study Arms (2)

Localized SCLC

EXPERIMENTAL

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

Extensive SCLC

OTHER

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

Interventions

acetazolamide in combination with radioimmunotherapy in patients with extensive SCLC DRUG

acetazolamide in combination with radioimmunotherapy in patients with extensive SCLC

Extensive SCLC

acetazolamide in combination with platinum and etoposide-based radiochemotherapy DRUG

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).

Localized SCLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Antoine Lacassagne: lead

Study Sites (2)

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Centre Hospitalier Princesse grace

Monte Carlo, Monaco

TERMINATED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Acetazolamide; Platinum; Radioimmunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Combined Modality Therapy; Radiotherapy

Study Officials

• Vanessa VIDAL

  Centre Antoine Lacassagne

  STUDY DIRECTOR

Central Study Contacts

Jérôme DOYEN, PH

CONTACT

+33492031270; jerome.doyen@nice.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I study with a prospective, multicenter, non randomized, open-label extension cohort, evaluating the safety of acetazolamide in combination with platinum and etoposide-based radiochemotherapy in patients with Localized Small cell lung cancer or in combinaison with radioimmunotherapy in patients with extensive Small cell lung cancer

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: March 16, 2018
• Study Start: August 2, 2019
• Primary Completion (Estimated): October 27, 2026
• Study Completion (Estimated): April 27, 2027
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1); FR (1)