Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Temporarily halted
Participants planned
27
Countries
1
Sites
1
lung carcinoma
The main objective is to determine the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of acetazolamide in combination with : - Radiotherapy combined with platinum-based chemotherapy and etoposide (subgroup "localised CPC"), - Radiation therapy combined with atezolizumab or durvalumab immunotherapy (extended CPC…
Key facts
- Sponsor
- Centre Antoine Lacassagne
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 27 Jan 2020 → ongoing
- Decision date (initial)
- 2023-02-09
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2022-503093-36-00
- EudraCT number
- 2017-002160-40
- ClinicalTrials.gov
- NCT03467360
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety
The main objective is to determine the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of acetazolamide in combination with :
- Radiotherapy combined with platinum-based chemotherapy and etoposide (subgroup "localised CPC"),
- Radiation therapy combined with atezolizumab or durvalumab immunotherapy (extended CPC subgroup).
Secondary objectives 8
- Defining the overall safety of acetazolamide in combination with radiochemotherapy
- To define the overall safety of acetazolamide in combination with radioimmunotherapy
- To assess the effectiveness of the treatment for the subgroups "localized CPC" and "extended CPC
- Identify predictive factors of response to acetazolamide for the subgroups "localized CPC" and "extensive CPC
- To assess progression-free survival at 24 months for the subgroups "localized CPC" and "extended CPC
- To assess the overall survival at 24 months for the subgroups "localized CPC" and "extended CPC"
- To determine compliance with acetazolamide for the subgroups "localized CPC" and "extended CPC
- To assess quality of life for the subgroups 'localised CPC' and 'extended CPC'
Conditions and MedDRA coding
lung carcinoma
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 13
- Age greater than or equal to 18 years,
- Performance Status 0 to 2,
- Measurable lesion according to RECIST 1.1 criteria and/or PERCIST 1.0 criteria
- If the patient is a woman of childbearing age, she must be surgically sterile or agree to use two adequate methods of contraception
- If the male patient has one or more female partners of childbearing age, he must agree to use an adequate method of contraception
- Patient affiliated to a social security scheme
- for localized CPC : Patient with histologically proven CPC, located in the chest, non-metastatic
- for localized CPC : Treatment-naive patient with localized CPC
- for localized CPC : Patient to be started on radiotherapy combined with platinum-based chemotherapy and etoposide
- for extended CPC Patient with histologically proven CPC, not localised to the chest,
- for extended CPC Patient eligible for first line chemoimmunotherapy,
- for extended CPC Patient who has received at least 1 cycle of chemoimmunotherapy (maximum 4 cycles) with platinum salts, etoposide and immunotherapy (atezolizumab or durvalumab) as first treatment for their extended CPC
- for extended CPC Patient responds or is stable according to RECIST 1.1 criteria and/or PERCIST 1.0 criteria after platinum-based chemoimmunotherapy, etoposide and immunotherapy (atezolizumab or durvalumab)
Exclusion criteria 4
- Previous thoracic irradiation or near/in the thoracic irradiation field, without possible re-irradiation
- Contraindication to thoracic radiotherapy treatment: unbalanced congestive heart failure (ejection fraction < 30%, clinical signs), severe respiratory failure
- Vulnerable persons
- for localized CPC : Patient with metastatic disease
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint will be based on the frequencies of dose-limiting toxicities determined during : - 6-7 weeks of acetazolamide/radiochemotherapy with platinum salts and etoposide and within the first 6 months after the last administration of radiochemotherapy, for the subgroup "localised CPC"; - The 10 days of acetazolamide/radio-immunotherapy treatment and within the first 6 months after the last administration of radio-immunotherapy, for the subgroup "extensive CPC".
Secondary endpoints 8
- The overall safety of acetazolamide in combination with radiochemotherapy throughout the duration of patient participation will be assessed by clinical, biological and paraclinical means (plethysmography) and rated according to the NCI CTCAE V4.03 scale
- The overall safety of acetazolamide in combination with radioimmunotherapy throughout the duration of patient participation will be assessed by clinical, biological and paraclinical means (plethysmography) and rated according to the NCI CTCAE V4.03 scale
- Tumour response (complete or partial, stabilisation, progression) will be assessed by morphological (RECIST 1.1) and metabolic (PERCIST 1.0) evaluations
- Evaluation of predictive factors for response to acetazolamide will be determined by serum CAIX and CAXII levels, and 18-FDG PET scan binding intensity (SUVmax; SULpeak)
- Progression-free survival at 24 months will be assessed by calculating the time from the date of inclusion to the date of progression or death from any cause.
- Overall survival at 24 months will be assessed by calculating the time from the date of inclusion to the date of death from all causes
- Compliance will be assessed using the Girerd questionnaire
- Quality of life will be assessed using the EORTC QLQ-C30 questionnaire
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD1167476 · Product
- Active substance
- Acetazolamide
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 1250 mg milligram(s)
- Max total dose
- 41250 mg milligram(s)
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- S01EC01 — ACETAZOLAMIDE
- Marketing authorisation
- 138101
- MA holder
- AMDIPHARM LIMITED
- MA country
- Luxembourg
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- associated to radiotherapy and for this medical condition
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Antoine Lacassagne
- Sponsor organisation
- Centre Antoine Lacassagne
- Address
- 33 Avenue De Valombrose
- City
- Nice Cedex 2
- Postcode
- 06189
- Country
- France
Scientific contact point
- Organisation
- Centre Antoine Lacassagne
- Contact name
- Pr Jérome DOYEN
Public contact point
- Organisation
- Centre Antoine Lacassagne
- Contact name
- Vanessa VIDAL
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Temporarily halted | 27 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Antoine Lacassagne
radiotherapy, 33 Avenue De Valombrose, 06189, Nice Cedex 2
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2020-01-27 | 2020-01-27 | 2024-12-19 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-65034
- Halt date
- 2024-12-19
- Member states concerned
- France
- Publication date
- 2024-12-31
- Reason
- Safety related (clinical or pre-clinical results)
- Explanation
- more than 33% of DLT has probably occured into the first dosing level of Diamox.
An IDMC will be conducted as soon as possible to evaluate the global safety profile of the treatment in this study before restarting (or not) the recruitment. - Follow-up measures
- Diamox has benn definitivley stopped and patients are in safety follow-up. Data analyses will be performed and results will be discussed during an Independant Data Monitoring Committee to decide the issue of the global study
- Benefit-risk balance changed
- Yes
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 34 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | 2022-503093-36-00_Protocole-clean-FP_ ICAR | 5.0 |
| Protocol (for publication) | 2022-503093-36-00_PROTOCOLE-FP_ICAR | 4.1 |
| Protocol (for publication) | 2022-503093-36-00_Protocole-TC-FP_ ICAR | 7.0 |
| Protocol (for publication) | Protocol_2022-503093-36-00 | 7.0 |
| Protocol (for publication) | Protocol-TC_2022-503093-36-00 | 6 |
| Recruitment arrangements (for publication) | 2017-002160-40_informedconsent_patientrecruitmentprocedure_ICAR | 1 |
| Recruitment arrangements (for publication) | 2022-503093-36-00_Courbe des inclusions_20230111_ICAR FP | 1 |
| Subject information and informed consent form (for publication) | 2017-002160-40_Carnet de releve de poids a domicile_version 3-0_20200707 | 1 |
| Subject information and informed consent form (for publication) | 2017-002160-40_Carnet de releve de poids au centre_version 3-0_20200707 | 1 |
| Subject information and informed consent form (for publication) | 2017-002160-40_carnet patient_version 2-0_20210824_ICAR | 1 |
| Subject information and informed consent form (for publication) | 2017-002160-40_carte patient-sous-groupe CPC etendu_version 1-0_20210727_ICAR | 1 |
| Subject information and informed consent form (for publication) | 2017-002160-40_carte patient-sous-groupe CPC localise_version 2-0_20210727_ICAR | 2.1 |
| Subject information and informed consent form (for publication) | 2017-002160-40_NI-CE_clean version 4-2_20220330_ICAR | 1 |
| Subject information and informed consent form (for publication) | 2017-002160-40_NI-NO-sous-groupe CPC etendu_clean version 1-1_20220330_ICAR | 1 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_Carnet de releve de poids a domicile_ICAR | 3 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_Carnet de releve de poids au centre_ICAR | 3 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_NI-CE_clean version_ICAR | 5 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_NI-CE_TC version_ICAR | 5 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_NI-NO_sous-groupe CPC etendu_clean version_ICAR | 2 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_NI-NO_sous-groupe CPC etendu_TC version_ICAR | 2 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_Ordonnance Diamox_CPC etendu_ICAR | 2 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_Ordonnance Diamox_CPC localise_ICAR | 3 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_Questionnaire evaluation tolerance_CPC etendu_ICAR | 2 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_Questionnaire evaluation tolerance_CPC localise_ICAR | 5 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_SOP relecture imagerie-FP_clean version_ICAR | 3 |
| Subject information and informed consent form (for publication) | 2022-503093-36-00_SOP relecture imagerie-FP_TC version_ICAR | 3 |
| Subject information and informed consent form (for publication) | SIS and ICF_2022-503093-36-00 | 7.0 |
| Subject information and informed consent form (for publication) | SIS and ICF_TC_2022-503093-36-00 | 7.0 |
| Summary of Product Characteristics (SmPC) (for publication) | 2017-002160-40_RCP Diamox_ICAR | 1 |
| Synopsis of the protocol (for publication) | 2022-503093-36-00_Synopsis-clean-FP_ ICAR | 5.0 |
| Synopsis of the protocol (for publication) | 2022-503093-36-00_SYNOPSIS-FP_ICAR | 4.1 |
| Synopsis of the protocol (for publication) | 2022-503093-36-00_Synopsis-TC-FP_ ICAR | 5.0 |
| Synopsis of the protocol (for publication) | Protocol synopsis_2022-503093-36-00 | 7.0 |
| Synopsis of the protocol (for publication) | Protocol synopsis-TC_2022-503093-36-00 | 7.0 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-12-22 | France | Acceptable 2023-02-06
|
2023-02-09 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-02-10 | France | Acceptable 2023-03-17
|
2023-05-03 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-01-16 | France | Acceptable 2024-03-18
|
2024-03-25 |
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-05-31 | France | Acceptable 2024-07-29
|
2024-07-29 |
| 5 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-07-16 | France | Acceptable 2025-08-07
|
2025-08-29 |