MESOTIP is a randomized trial evaluating the association of PIPAC and systemic chemotherapy versus systemic chemotherapy alone as 1st-line treatment of Malignant Peritoneal Mesothelioma In this study, patients in the experimental arm will be treated by 4 PIPAC (Cisplatine+Doxorubicine) alternating with 6 cycles of standard intravenous chemotherapy (Cisplatine+Pemetrexed).
MESOTIP aim to show an improvement of the overall survival in the experimental arm.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Peritoneal Mesothelioma Peritoneal Carcinomatosis | Procedure: PIPAC Drug: Cisplatin Drug: Pemetrexed | Phase 2 |
Malignant peritoneal mesothelioma (MPM) is a rare tumoral disease characterized by the diffuse involvement of the peritoneal serosa. The incidence of all mesotheliomas is estimated quite differently in various reports with the highest rates in industrialized countries. In France, the estimated incidence is 300 cases/year. Three types of malignant mesotheliomas are described in the WHO classification: epithelioid, sarcomatoid and biphasic.
The standard treatment of MPM is surgery. It has been shown that cytoreductive surgery (CRS) associated to hyperthermic intraperitoneal chemotherapy (HIPEC) improves prognosis resulting in a median overall survival of 29.5 months to 53 months and an 5 years overall survival rate ranging between 39 to 63%. Cytoreductive surgery should be complete or almost complete (CCR0/1) as macroscopic residual disease deteriorates prognosis.
However some patients are not eligible for surgery due to the locoregional extension of the disease. Although debulking surgery may still be considered, its results are less encouraging than CRS and HIPEC.
The neoadjuvant treatment combining Cisplatin and Pemetrexed became a routinely applied option for initially unresectable patients after the publication of an open-label study inspired by previous results of a randomized trial in pleural mesothelioma. This study showed a benefit in median survival of 5 months and an increase in the response rate of 10%. Ever since, other phase II studies were proposed but their benefit is still limited. Pleural mesothelioma which is more common and represents the model of choice for the treatment of peritoneal mesothelioma has also benefitted from phase III studies analyzing the addition of a targeted therapy (Bevacizumab) and phase II trials proposing immunotherapy.
By contrast, peritoneal mesothelioma was the setting of choice for testing intraperitoneal administration of chemotherapy either as early postoperative intraperitoneal chemotherapy (EPIC) or as neoadjuvant intraperitoneal chemotherapy. Both studies offered promising results showing a sensitivity of MPM to intraperitoneal administration.
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) has recently been developed and shows interesting results in the neoadjuvant context of several peritoneal carcinomatoses while producing little toxicity. PIPAC is a modality of repeated administration of intraperitoneal chemotherapy during laparoscopy using aerosols at the pressure of the capnoperitoneum (12mmHg). Data from ex-vivo, in-vivo and human studies demonstrated a higher local drug bioavailability when compared to liquid IP chemotherapy. PIPAC was tested in the setting of malignant mesothelioma showing encouraging results.
In our study MESOTIP, patients in the experimental arm will be treated by 4 PIPAC (Cisplatine+Doxorubicine) alternating with 6 cycles of standard intravenous chemotherapy (Cisplatine+Pemetrexed).
Although retrospective reports showing the interest of PIPAC in the neoadjuvant setting for different peritoneal carcinomatosis origins were published, MESOTIP would be the first study to combine PIPAC to systemic chemotherapy in the first-line of treatment and to only include patients not eligible for surgical treatment and proposing a complete cytoreductive surgery associated to HIPEC for patients converted to resectability.
MESOTIP aim to show an improvement of the overall survival in the experimental arm.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 66 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase II Multicenter Randomized Trial Evaluating the Association of PIPAC and Systemic Chemotherapy Versus Systemic Chemotherapy Alone as 1st-line Treatment of Malignant Peritoneal Mesothelioma |
Actual Study Start Date : | August 14, 2020 |
Estimated Primary Completion Date : | June 2022 |
Estimated Study Completion Date : | December 2024 |
Arm | Intervention/treatment |
---|---|
Experimental: association of PIPAC and systemic chemotherapy
4 PIPAC of Cisplatin 10.5mg/m² + Doxorubicin 2.1 mg/m² every 6 weeks alternating with standard intravenous chemotherapy for mesothelioma (Cisplatin 75mg/m² + Pemetrexed 500mg/m²)
|
Procedure: PIPAC
Pressurized IntraPeritoneal Aerosol Chemotherapy of Cisplatin 10.5mg/m² + Doxorubicin 2.1 mg/m² every 6 weeks
Other Names:
Drug: Cisplatin standard intravenous chemotherapy for mesothelioma (Cisplatin 75mg/m² + Pemetrexed 500mg/m²)
Drug: Pemetrexed standard intravenous chemotherapy for mesothelioma (Cisplatin 75mg/m² + Pemetrexed 500mg/m²)
|
Active Comparator: systemic chemotherapy alone
6 cycles of Cisplatin 75mg/m² + Pemetrexed 500mg/m²
|
Drug: Cisplatin
standard intravenous chemotherapy for mesothelioma (Cisplatin 75mg/m² + Pemetrexed 500mg/m²)
Drug: Pemetrexed standard intravenous chemotherapy for mesothelioma (Cisplatin 75mg/m² + Pemetrexed 500mg/m²)
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Olivia SGARBURA, MD | 0467614586 ext +33 | Olivia.sgarbura@icm.unicancer.fr |
France | |
Institut réginal du Cancer de Montpellier | Recruiting |
Montpellier, France, 34298 | |
Contact: Olivia SGARBURA 0033467613102 olivia.sgarbura@icm.unicancer.fr |
Principal Investigator: | Olivia SGARBURA, MD | Institut régional du Cancer de Montpellier |
Tracking Information | |||||
---|---|---|---|---|---|
First Submitted Date ICMJE | March 4, 2019 | ||||
First Posted Date ICMJE | March 14, 2019 | ||||
Last Update Posted Date | September 16, 2020 | ||||
Actual Study Start Date ICMJE | August 14, 2020 | ||||
Estimated Primary Completion Date | June 2022 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
overall survival [ Time Frame: from randomization of first patient until the database cut-off ] The overall survival is defined as the time from the date of randomization to the date of death from any cause
|
||||
Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
|
||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Treatment of Malignant Peritoneal Mesothelioma (MESOTIP) | ||||
Official Title ICMJE | Phase II Multicenter Randomized Trial Evaluating the Association of PIPAC and Systemic Chemotherapy Versus Systemic Chemotherapy Alone as 1st-line Treatment of Malignant Peritoneal Mesothelioma | ||||
Brief Summary |
MESOTIP is a randomized trial evaluating the association of PIPAC and systemic chemotherapy versus systemic chemotherapy alone as 1st-line treatment of Malignant Peritoneal Mesothelioma In this study, patients in the experimental arm will be treated by 4 PIPAC (Cisplatine+Doxorubicine) alternating with 6 cycles of standard intravenous chemotherapy (Cisplatine+Pemetrexed). MESOTIP aim to show an improvement of the overall survival in the experimental arm. |
||||
Detailed Description |
Malignant peritoneal mesothelioma (MPM) is a rare tumoral disease characterized by the diffuse involvement of the peritoneal serosa. The incidence of all mesotheliomas is estimated quite differently in various reports with the highest rates in industrialized countries. In France, the estimated incidence is 300 cases/year. Three types of malignant mesotheliomas are described in the WHO classification: epithelioid, sarcomatoid and biphasic. The standard treatment of MPM is surgery. It has been shown that cytoreductive surgery (CRS) associated to hyperthermic intraperitoneal chemotherapy (HIPEC) improves prognosis resulting in a median overall survival of 29.5 months to 53 months and an 5 years overall survival rate ranging between 39 to 63%. Cytoreductive surgery should be complete or almost complete (CCR0/1) as macroscopic residual disease deteriorates prognosis. However some patients are not eligible for surgery due to the locoregional extension of the disease. Although debulking surgery may still be considered, its results are less encouraging than CRS and HIPEC. The neoadjuvant treatment combining Cisplatin and Pemetrexed became a routinely applied option for initially unresectable patients after the publication of an open-label study inspired by previous results of a randomized trial in pleural mesothelioma. This study showed a benefit in median survival of 5 months and an increase in the response rate of 10%. Ever since, other phase II studies were proposed but their benefit is still limited. Pleural mesothelioma which is more common and represents the model of choice for the treatment of peritoneal mesothelioma has also benefitted from phase III studies analyzing the addition of a targeted therapy (Bevacizumab) and phase II trials proposing immunotherapy. By contrast, peritoneal mesothelioma was the setting of choice for testing intraperitoneal administration of chemotherapy either as early postoperative intraperitoneal chemotherapy (EPIC) or as neoadjuvant intraperitoneal chemotherapy. Both studies offered promising results showing a sensitivity of MPM to intraperitoneal administration. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) has recently been developed and shows interesting results in the neoadjuvant context of several peritoneal carcinomatoses while producing little toxicity. PIPAC is a modality of repeated administration of intraperitoneal chemotherapy during laparoscopy using aerosols at the pressure of the capnoperitoneum (12mmHg). Data from ex-vivo, in-vivo and human studies demonstrated a higher local drug bioavailability when compared to liquid IP chemotherapy. PIPAC was tested in the setting of malignant mesothelioma showing encouraging results. In our study MESOTIP, patients in the experimental arm will be treated by 4 PIPAC (Cisplatine+Doxorubicine) alternating with 6 cycles of standard intravenous chemotherapy (Cisplatine+Pemetrexed). Although retrospective reports showing the interest of PIPAC in the neoadjuvant setting for different peritoneal carcinomatosis origins were published, MESOTIP would be the first study to combine PIPAC to systemic chemotherapy in the first-line of treatment and to only include patients not eligible for surgical treatment and proposing a complete cytoreductive surgery associated to HIPEC for patients converted to resectability. MESOTIP aim to show an improvement of the overall survival in the experimental arm. |
||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||
Condition ICMJE |
|
||||
Intervention ICMJE |
|
||||
Study Arms ICMJE |
|
||||
Publications * |
|
||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||
Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
66 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | December 2024 | ||||
Estimated Primary Completion Date | June 2022 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||
Sex/Gender ICMJE |
|
||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
|
||||
Listed Location Countries ICMJE | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03875144 | ||||
Other Study ID Numbers ICMJE | PROICM 2019-03 MES | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
|
||||
IPD Sharing Statement ICMJE |
|
||||
Responsible Party | Institut du Cancer de Montpellier - Val d'Aurelle | ||||
Study Sponsor ICMJE | Institut du Cancer de Montpellier - Val d'Aurelle | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
|
||||
PRS Account | Institut du Cancer de Montpellier - Val d'Aurelle | ||||
Verification Date | August 2020 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |