A Phase 2/3 interventional study of ADI-PEG 20 plus Pem Platinum and Placebo plus Pem Platinum in Mesothelioma, sponsored by Polaris Group. Completed at 45 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-04.
Sponsored by Polaris Group · Phase 2/3, Interventional, and Treatment
This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the malignant pleural mesothelioma cells will starve and die.
305 studies on the registry are indexed under Mesothelioma; 61 are open to participants now.
This study's enrollment of 249 is above the median of 48 across 250 interventional studies indexed under Mesothelioma.
Browse Mesothelioma studies →Polaris Group is the lead sponsor of 20 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Duration : Course of Study In Combination With: Pemetrexed Dose: 500 mg/m2 every 3 weeks Route of Administration: Intravenous Cisplatin Dose: 75 mg/m2 every 3 weeks Route of Administration: Intravenous Carboplatin Dose: AUC 5 mg/mL/min every 3 weeks Route of Administration: Intravenous ADI-PEG 20 plus Pem Platinum: Investigational Drug in combination approved standard of care treatment for this indication
Drug: ADI-PEG 20 plus Pem Platinum
Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Duration : Course of Study In Combination With: Pemetrexed Dose: 500 mg/m2 every 3 weeks Route of Administration: Intravenous Cisplatin Dose: 75 mg/m2 every 3 weeks Carboplatin Dose: AUC 5 mg/mL/min every 3 weeks Route of Administration: Intravenous Placebo plus Pem Platinum: Placebo in combination approved standard of care treatment for this indication
Other: Placebo plus Pem Platinum
Drug page: Pemetrexed
Investigational Drug in combination approved standard of care treatment for this indication
Also known as: Pemetrexed, Cisplatin, Carboplatin
Placebo in combination approved standard of care treatment for this indication
Also known as: Pemetrexed, Cisplatin, Carboplatin
Response Rate
Objective Response Rate is calculated as the proportion of subjects whose best tumor response from all post-baseline tumor assessments is complete response (CR) or partial response (PR). The best tumor response is the best response recorded from the start of the treatment until the end of treatment taking into account any requirement for confirmation. To test Objective Response Rate significance, a Relative Risk Ratio (ADI-PEG 20 / Placebo) was calculated as the common relative risk of having a response (CR or PR) based on the Mantel-Haenszel estimator controlling for tumor histology (biphasic versus sarcomatoid).
Time frame: approximately 18 months
Overall Survival Phase 3 Interim Analysis
The primary analysis of OS Phase 3 was performed at the interim analysis. This was performed once 50% of the planned OS events for phase 3 have occurred (ie, 169 of the 338 planned OS events). This interim analysis will evaluate OS in the ITT population in an unblinded manner. The OS data at the second interim analysis will be analyzed to support the following decisions: Futility stopping: Terminate the study due to futility at the interim analysis. Sample size re-estimation: Increase the target number of OS events after the second interim analysis.. The treatment effect on OS will be evaluated using the stratified log-rank test (stratified by tumor histology).
Time frame: Approximately 18 months
Overall Survival
Overall survival is defined as the time from randomization until death. In the event that no death was documented prior to study termination or analysis cutoff, OS was censored at the last known date the subject was known to be alive, either through completion of on-study visits or through survival follow-up contact. The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology). The Kaplan-Meier curves were also plotted. A Cox proportional hazard model with an adjustment for tumor histology (biphasic vs sarcomatoid) was used to compute the estimated hazard ratio and two-sided 95% CI. The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology). The significance level to be used in the OS analysis at the final analysis was based on α = 0.04999 (two-sided).
Time frame: 18 months
Progression Free Survival
The key secondary endpoint for the phase 3 portion is PFS, which will be analyzed only if the analysis of OS is statistically significant at the final analysis, with alpha level of 0.05 (two-sided) using the same statistical methodologies as applied to OS.
Time frame: approximately 18 months
| Milestone | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum |
|---|---|---|
| Started | 87 | 89 |
| Completed | 87 | 89 |
| Not completed | 0 | 0 |
| Milestone | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum |
|---|---|---|
| Started | 125 | 124 |
| Completed | 125 | 124 |
| Not completed | 0 | 0 |
Objective Response Rate is calculated as the proportion of subjects whose best tumor response from all post-baseline tumor assessments is complete response (CR) or partial response (PR). The best tumor response is the best response recorded from the start of the treatment until the end of treatment taking into account any requirement for confirmation. To test Objective Response Rate significance, a Relative Risk Ratio (ADI-PEG 20 / Placebo) was calculated as the common relative risk of having a response (CR or PR) based on the Mantel-Haenszel estimator controlling for tumor histology (biphasic versus sarcomatoid).
| Participants | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum |
|---|---|---|
| Response Rate | 12 | 12 |
The primary analysis of OS Phase 3 was performed at the interim analysis. This was performed once 50% of the planned OS events for phase 3 have occurred (ie, 169 of the 338 planned OS events). This interim analysis will evaluate OS in the ITT population in an unblinded manner. The OS data at the second interim analysis will be analyzed to support the following decisions: Futility stopping: Terminate the study due to futility at the interim analysis. Sample size re-estimation: Increase the target number of OS events after the second interim analysis.. The treatment effect on OS will be evaluated using the stratified log-rank test (stratified by tumor histology).
| months | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum |
|---|---|---|
| Overall Survival Phase 3 Interim Analysis | 9.82 (7.85 to 12.91) | 7.49 (5.88 to 9.46) |
Overall survival is defined as the time from randomization until death. In the event that no death was documented prior to study termination or analysis cutoff, OS was censored at the last known date the subject was known to be alive, either through completion of on-study visits or through survival follow-up contact. The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology). The Kaplan-Meier curves were also plotted. A Cox proportional hazard model with an adjustment for tumor histology (biphasic vs sarcomatoid) was used to compute the estimated hazard ratio and two-sided 95% CI. The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology). The significance level to be used in the OS analysis at the final analysis was based on α = 0.04999 (two-sided).
| months | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum |
|---|---|---|
| Overall Survival | 9.30 (7.85 to 11.79) | 7.66 (6.14 to 9.53) |
The key secondary endpoint for the phase 3 portion is PFS, which will be analyzed only if the analysis of OS is statistically significant at the final analysis, with alpha level of 0.05 (two-sided) using the same statistical methodologies as applied to OS.
| months | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum |
|---|---|---|
| Progression Free Survival | 6.24 (5.78 to 7.43) | 5.65 (4.14 to 5.91) |
Collected over Treatment-emergent AEs were collected with onset after the first dose of study drug or existing events that worsened after the first dose during the study, approximately 18 months.. Non-serious events are listed at a 2.5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Drug: ADI-PEG 20 Plus Pem Platinum | 62/125 (49.6%) | 19/125 (15.2%) | 106/125 (84.8%) |
| Drug: Placebo Plus Pem Platinum | 61/124 (49.2%) | 20/124 (16.1%) | 111/124 (89.5%) |
| Event | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum |
|---|---|---|
| PyrexiaGeneral disorders | 5/125 | 8/124 |
| NauseaGastrointestinal disorders | 1/125 | 7/124 |
| PneumoniaInfections and infestations | 5/125 | 6/124 |
| SepsisInfections and infestations | 1/125 | 6/124 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 6/125 | 2/124 |
| Acute Kidney InjuryRenal and urinary disorders | 6/125 | 4/124 |
| AnemiaBlood and lymphatic system disorders | 0/125 | 5/124 |
| Atrial FibrillationCardiac disorders | 4/125 | 0/124 |
| DehydrationMetabolism and nutrition disorders | 0/125 | 3/124 |
| Musculoskeletal TestingMusculoskeletal and connective tissue disorders | 1/125 | 3/124 |
| Event | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum |
|---|---|---|
| NauseaGastrointestinal disorders | 65/125 | 67/124 |
| FatigueGeneral disorders | 66/125 | 62/124 |
| ConstipationGastrointestinal disorders | 54/125 | 41/124 |
| Decreased AppetiteMetabolism and nutrition disorders | 26/125 | 44/124 |
| AnemiaBlood and lymphatic system disorders | 34/125 | 38/124 |
| Age, Continuous(years) | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum | Total |
|---|---|---|---|
| Mean | 69.5 ± 7.98 | 69.4 ± 7.91 | 69.4 ± 7.93 |
| Sex: Female, Male(Participants) | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum | Total |
|---|---|---|---|
| Female | 23 | 20 | 43 |
| Male | 102 | 104 | 206 |
| Ethnicity (NIH/OMB)(Participants) | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 2 | 4 |
| Not Hispanic or Latino | 119 | 117 | 236 |
| Unknown or Not Reported | 4 | 5 | 9 |
| Race (NIH/OMB)(Participants) | Drug: ADI-PEG 20 Plus Pem Platinum | Drug: Placebo Plus Pem Platinum | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 5 | 5 | 10 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 0 | 3 |
| White | 116 | 116 | 232 |
| More than one race | 1 | 3 | 4 |
| Unknown or Not Reported | 0 | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Aug 2017 to primary completion in Aug 2022, 60 months.
Results were first posted in Oct 2023, 1 year 1 month after primary completion.
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Studies of the drug tested here: Pemetrexed
Polaris Group