Malignant Pleural MesotheliomaPhase 1NCT00571298
Extrapleural Pneumonectomy /Pleurectomy Decortication, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma
A Phase 1 study testing Extrapleural pneumonectomy (EPP), Cisplatin and gemcitabine in people with Malignant Pleural Mesothelioma, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
RATIONALE: After removal of visible cancer in the chest, chemotherapy drugs are used to kill or stop tumor cells from dividing, so that they stop growing or/and die. Cisplatin is currently used safely as in intra-operative treatment for malignant pleural mesothelioma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Pleural Mesothelioma
- What is being tested?
- Extrapleural pneumonectomy (EPP), Cisplatin and gemcitabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 141 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Jun 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically-proven diagnosis of stages I to III malignant mesothelioma of the pleura and negative mediastinal N2 lymph nodes (Malignancy is confined to the affected hemithorax)
- Adequate organ function including the following: adequate cardiac function, pulmonary function, renal and hepatic function and bone marrow reserve
- Adequate overall physical activity
- Surgical candidate for cytoreductive surgery
Who cannot join
- Extended disease outside the ipsilateral hemithorax as proven histologically, radiologically and/or intraoperatively
- Have received chemotherapy and or radiation therapy within the last 3 years at the time of study entry
- Serious concomitant systemic disorders
- Second active primary malignancy (to exclude non- melanoma skin cancer)
- Pregnancy at the time of the operation
- Psychiatric or addictive disorder which would preclude obtaining informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: A Phase I Trial of Extrapleural Pneumonectomy/Pleurectomy Decortication, Intrathoracic/Intraperitoneal Hyperthermic (IOHC) Cisplatin and Gemcitabine With Intravenous Amifostine and Sodium Thiosulfate Cytoprotection for Patients With Resectable Malignant Pleural Mesothelioma
RATIONALE: After removal of visible cancer in the chest, chemotherapy drugs are used to kill or stop tumor cells from dividing, so that they stop growing or/and die. Cisplatin is currently used safely as in intra-operative treatment for malignant pleural mesothelioma. This study is aimed to determine if the addition of gemcitabine as a second intracavitary chemotherapy can be accomplished safely.
PURPOSE: This is a Phase I trial to study the efficacy of combination chemotherapy consisting of gemcitabine and cisplatin administered in the operating room and put into the chest and abdomen for one hour. We are also looking at the effects of heating the chemotherapy to a temperature of 42 degrees Celsius and the effect of cytoprotection agents: amifostine and sodium thiosulfate to counteract potential side effects of chemotherapy.
Read the detailed description
- This is a dose escalation study of gemcitabine with a fixed dose of cisplatin
- Patients will undergo cytoreductive surgery, which entails the removal of the inner and outer lining of the lung (pleurectomy/decortication) with or without the lung itself (extrapleural pneumonectomy), including the lining overlying the pericardium and diaphragm. Resection of the pericardium and diaphragm are occasionally necessary to remove all visable tumor. This surgery is part of standard care for malignant pleural mesothelioma.
- After surgery, a one hour lavage with heated cisplatin and or gemcitabine will be administered to the hemithorax (and abdominal regions if the diaphragm is no longer present).
- Patients will remain hospitalized until they have recovered from surgery (usually 7-14 days).
- Patients will return to the hospital during the first month after their surgery to be evaluated by the medical staff.
- Dose escalation: 1) Three patients will be treated at the first dose level of gemcitabine. Labs will be monitored on a weekly basis, including a CBC, Chem-7, and LFT's. In the absence of developing dose-limiting toxicity (DLT) among the first 3 patients treated, dosages can be escalated. DLT will be defined as any grade 3 or higher renal toxicity, thrombocytopenia or other grade 3 toxicity not related to surgery 2) If none of these 3 patients have any toxicity, we will proceed to the next level of gemcitabine. 3) If DLT occurs in 1 of 3 patients at a given dose level, then 3 additional patients are added at that dose (for a total of 6 at this level)If no DLT occurs, we will proceed to the next level of gemcitabine. If DLT occurs in another patient, this dose is considered the maximum tolerated dose (MTD). 4) At any dose, 3 cases of DLT lead to discontinuation of recruitment at that dose and enrollment of 3 additional patients at a lower dose.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- Extrapleural pneumonectomy (EPP), Cisplatin, gemcitabine, amifostine, sodium thiosulfate
- Keywords
- Extrapleural pneumonectomy, Pleurectomy Decortication, Mesothelioma, cisplatin, gemcitabine, amifostine, sodium thiosulfate
- Medical subject headings
- Mesothelioma, Malignant, Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extrapleural pneumonectomy (EPP)Procedure or surgery
Resection of the lung, the lining of the lung (pleura), the covering of the heart (pericardium), and the muscle that separates the chest and abdomen (diaphragm)
CisplatinDrug
Also called Platinol
Given after the tumor is removed as a bath (perfusion) for one-hour
gemcitabineDrug
Also called Gemzar
Given after the tumor is removed as a bath (perfusion) for one-hour
amifostineDrug
Given intravenously before perfusion chemotherapy and then 2 hours after the first dose
sodium thiosulfateDrug
Given intravenously immediately at the end of perfusion chemotherapy
Pleurectomy/DecorticationProcedure or surgery
Resection of the lining of the lung (pleura), while the lung remains intact.
| Study group | Role | What they receive |
|---|---|---|
| Extrapleural pneumonectomy (EPP) | Experimental | This is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate Receives: Procedure: Extrapleural pneumonectomy (EPP); Drug: Cisplatin; Drug: gemcitabine; Drug: amifostine; Drug: sodium thiosulfate |
| Pleurectomy/Decortication (P/DC) | Experimental | This is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate Receives: Drug: Cisplatin; Drug: gemcitabine; Drug: amifostine; Drug: sodium thiosulfate; Procedure: Pleurectomy/Decortication |
| Tumor Debulking (TD) | Experimental | This is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate Receives: Drug: Cisplatin; Drug: gemcitabine; Drug: amifostine; Drug: sodium thiosulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish the maximally tolerated dose (MTD) of intraoperative Intrathoracic/Intraperitoneal hyperthermic gemcitabine and cisplatin combination modulated by amifostine and sodium thiosulfate in patients with malignant pleural mesothelioma.
Measured: 2 years
Secondary outcomes (2)
To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity.
Measured: 2 years
To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2007 (estimated)
- Study startNov 2007
- Primary completionNov 2011
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Responsible party
- Principal investigator, Raphael Bueno, MD, Dana-Farber Cancer Institute
- Investigators
- Raphael Bueno, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00571298
- Sponsor's protocol ID
- 07-091
- Status last verified
- Jan 2017
- First submitted
- 10 Dec 2007
- Last updated
- 23 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Extrapleural Pneumonectomy/Pleurectomy Decortication, Intrathoracic/Intraperitoneal Hyperthermic (IOHC) Cisplatin and Gemcitabine With Intravenous Amifostine and Sodium Thiosulfate Cytoprotection for Patients With Resectable Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT00571298
- Acronym / sponsor ID
- 07-091
- Conditions
- Malignant Pleural Mesothelioma
- Keywords
- Extrapleural pneumonectomy, Pleurectomy Decortication, Mesothelioma, cisplatin, gemcitabine, amifostine, sodium thiosulfate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Study start
- Nov 2007
- Primary completion
- Nov 2011 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 11 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: After removal of visible cancer in the chest, chemotherapy drugs are used to kill or stop tumor cells from dividing, so that they stop growing or/and die. Cisplatin is currently used safely as in intra-operative treatment for malignant pleural mesothelioma. This study is aimed to determine if the addition of gemcitabine as a second intracavitary chemotherapy can be accomplished safely.
PURPOSE: This is a Phase I trial to study the efficacy of combination chemotherapy consisting of gemcitabine and cisplatin administered in the operating room and put into the chest and abdomen for one hour. We are also looking at the effects of heating the chemotherapy to a temperature of 42 degrees Celsius and the effect of cytoprotection agents: amifostine and sodium thiosulfate to counteract potential side effects of chemotherapy.
Detailed description
- This is a dose escalation study of gemcitabine with a fixed dose of cisplatin
- Patients will undergo cytoreductive surgery, which entails the removal of the inner and outer lining of the lung (pleurectomy/decortication) with or without the lung itself (extrapleural pneumonectomy), including the lining overlying the pericardium and diaphragm. Resection of the pericardium and diaphragm are occasionally necessary to remove all visable tumor. This surgery is part of standard care for malignant pleural mesothelioma.
- After surgery, a one hour lavage with heated cisplatin and or gemcitabine will be administered to the hemithorax (and abdominal regions if the diaphragm is no longer present).
- Patients will remain hospitalized until they have recovered from surgery (usually 7-14 days).
- Patients will return to the hospital during the first month after their surgery to be evaluated by the medical staff.
- Dose escalation: 1) Three patients will be treated at the first dose level of gemcitabine. Labs will be monitored on a weekly basis, including a CBC, Chem-7, and LFT's. In the absence of developing dose-limiting toxicity (DLT) among the first 3 patients treated, dosages can be escalated. DLT will be defined as any grade 3 or higher renal toxicity, thrombocytopenia or other grade 3 toxicity not related to surgery 2) If none of these 3 patients have any toxicity, we will proceed to the next level of gemcitabine. 3) If DLT occurs in 1 of 3 patients at a given dose level, then 3 additional patients are added at that dose (for a total of 6 at this level)If no DLT occurs, we will proceed to the next level of gemcitabine. If DLT occurs in another patient, this dose is considered the maximum tolerated dose (MTD). 4) At any dose, 3 cases of DLT lead to discontinuation of recruitment at that dose and enrollment of 3 additional patients at a lower dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Extrapleural pneumonectomy (EPP) | Experimental | Procedure: Extrapleural pneumonectomy (EPP), Drug: Cisplatin, Drug: gemcitabine, Drug: amifostine, Drug: sodium thiosulfateThis is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate |
| Pleurectomy/Decortication (P/DC) | Experimental | Drug: Cisplatin, Drug: gemcitabine, Drug: amifostine, Drug: sodium thiosulfate, Procedure: Pleurectomy/DecorticationThis is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate |
| Tumor Debulking (TD) | Experimental | Drug: Cisplatin, Drug: gemcitabine, Drug: amifostine, Drug: sodium thiosulfateThis is dose escalation 3+3 study design. All the patients meet the eligibility criteria and then sign the informed consent. Then after they have completed their standard pre-operative evalutions were each brought to the operating room for this surgical resection. Regardless of the arm the subject is assigned to they all recieve surgical intervention (Extrapleural Pneumonectomy, Pleurectomy/Decortication, or Tumor Debulking), Amifostine, Cisplatin, Gemcitabine, and Sodium Thiosulfate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically-proven diagnosis of stages I to III malignant mesothelioma of the pleura and negative mediastinal N2 lymph nodes (Malignancy is confined to the affected hemithorax)
- Adequate organ function including the following: adequate cardiac function, pulmonary function, renal and hepatic function and bone marrow reserve
- Adequate overall physical activity
- Surgical candidate for cytoreductive surgery
Key exclusion criteria (6 listed)
- Extended disease outside the ipsilateral hemithorax as proven histologically, radiologically and/or intraoperatively
- Have received chemotherapy and or radiation therapy within the last 3 years at the time of study entry
- Serious concomitant systemic disorders
- Second active primary malignancy (to exclude non- melanoma skin cancer)
- Pregnancy at the time of the operation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extrapleural pneumonectomy (EPP)Resection of the lung, the lining of the lung (pleura), the covering of the heart (pericardium), and the muscle that separates the chest and abdomen (diaphragm) | Procedure or surgery | Extrapleural pneumonectomy (EPP) |
| CisplatinAlso: PlatinolGiven after the tumor is removed as a bath (perfusion) for one-hour | Drug | Extrapleural pneumonectomy (EPP), Pleurectomy/Decortication (P/DC), Tumor Debulking (TD) |
| gemcitabineAlso: GemzarGiven after the tumor is removed as a bath (perfusion) for one-hour | Drug | Extrapleural pneumonectomy (EPP), Pleurectomy/Decortication (P/DC), Tumor Debulking (TD) |
| amifostineGiven intravenously before perfusion chemotherapy and then 2 hours after the first dose | Drug | Extrapleural pneumonectomy (EPP), Pleurectomy/Decortication (P/DC), Tumor Debulking (TD) |
| sodium thiosulfateGiven intravenously immediately at the end of perfusion chemotherapy | Drug | Extrapleural pneumonectomy (EPP), Pleurectomy/Decortication (P/DC), Tumor Debulking (TD) |
| Pleurectomy/DecorticationResection of the lining of the lung (pleura), while the lung remains intact. | Procedure or surgery | Pleurectomy/Decortication (P/DC) |
Primary outcome
To establish the maximally tolerated dose (MTD) of intraoperative Intrathoracic/Intraperitoneal hyperthermic gemcitabine and cisplatin combination modulated by amifostine and sodium thiosulfate in patients with malignant pleural mesothelioma.
Time frame: 2 years
2 secondary outcomes
To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity.
Time frame: 2 years
To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2017.
- Brigham and Women's Hospital, Mesothelioma and International Mesothelioma ProgramLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raphael Bueno, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Extrapleural pneumonectomy (EPP), Cisplatin and gemcitabine in people with Malignant Pleural Mesothelioma, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To establish the maximally tolerated dose (MTD) of intraoperative Intrathoracic/Intraperitoneal hyperthermic gemcitabine and cisplatin combination modulated by amifostine and sodium thiosulfate in patients with malignant pleural mesothelioma. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2017.