Malignant Pleural MesotheliomaPhase 2ADAMNCT01279967
A Clinical Trial of ADI-PEG 20TM in Patients With Malignant Pleural Mesothelioma
A Phase 2 study testing ADI-PEG 20 in people with Malignant Pleural Mesothelioma, run by Barts & The London NHS Trust at 7 sites in United Kingdom.
Trial summary
To examine whether the arginine depleting drug, ADI-PEG 20, might be effective as a targeted therapy in patients with ASS-negative 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?
- ADI-PEG 20
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 7 sitesUnited Kingdom
- Study dates
- Jan 2011to Mar 2015
- Phase
- Phase 2
- 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
- Males and Females aged 18 years and older. (There is no upper age limit)
- Histopathological evidence of ASS-negative MPM. All biopsies will be reviewed for ASS expression using immunohistochemistry. Central lab confirmation is required before randomization
- Performance status ECOG ≤ 1. Life expectancy should be greater than 3 months
- Chemo-naive patients OR, Patients who have been previously treated with platinum-based combination chemotherapy with progressive disease at entry. In the event of a baseline diagnostic ASS-positive test, a repeat biopsy confirming loss of ASS expression will be required post platinum-based combination chemotherapy, with at least a 4 week interval from the last treatment episode.
- CT evaluable disease by modified RECIST criteria
- Adequate bone marrow function, or supported through treatment:
Show all 12Show fewer
- Haemoglobin 10g/dl or greater.
- White cell count 2 x 109/L or greater, neutrophil count 1.5 x 109/L or greater
- Platelets 75 x 109 /L or greater.
- Adequate hepatic function (AST and ALT < 3 x upper limit of normal; bilirubin < 1.5 x upper limit of normal)
- Creatinine clearance >30ml/min
- Able to give written informed consent to participate
Who cannot join
- Participation in another clinical trial using an investigational agent
- Patients with surgically resectable disease
- Recurrent pleural effusion (not pleurodesed)
- Receipt of extensive radiation (hemi-thorax) therapy within 6 weeks before enrollment. Radiation to chest port sites following thoracotomy is permitted
- A history of prior malignant tumour, unless the patient has been without evidence of disease for at least three years, or the tumour was a non-melanoma skin tumour or in-situ cervix carcinoma
- Symptomatic or known brain or leptomeningeal metastases
Show all 16Show fewer
- Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment
- New York Heart Association (NYHA) Class III or IV heart failure (Attachment 10, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
- Serious medical (e.g. uncontrolled diabetes, hepatic disease, infection, uncontrolled gout) or psychiatric illness likely to interfere with participation in this clinical study
- History of seizures
- Patients of child-bearing age must not become pregnant. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. All patients enrolled on the study must agree to use acceptable birth control measures whilst on the study; using both barrier and hormonal methods. Patients that are surgically sterile are also eligible to participate in this study
- Females must not be breastfeeding
- Prior exposure to ADI-PEG 20
- Preplanned surgery or procedures that would interfere with the study protocol
- Allergy to pegylated products
- Exposure to another investigational drug within 4 weeks prior to start of study treatment
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United Kingdom7 sites
The Royal Sussex County Hospital
Brighton, BN2 5BE
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
Cambridge, CB2 0QQ
Hull and East Yorkshire Hospitals NHS Trust,The Princess Royal Hospital
Hull, HU8 9HE
Barts and The London NHS, St Bartholomew's Hospital
London, EC1 A 7BE
Guy's and St Thomas' Foundation Trust, Guy's Hospital
London, SE1 9RT
University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital
Manchester, M23 9LT
Southampton University Hospitals NHS Trust, Southampton General Hospital
Southampton, SO16 6 YD
About this study
Official title: A Randomized Stratified Multicentre Phase II Clinical Trial of Single Agent ADI-PEG 20TM (Pegylated Arginine Deiminase) in Patients With Malignant Pleural Mesothelioma
To examine whether the arginine depleting drug, ADI-PEG 20, might be effective as a targeted therapy in patients with ASS-negative malignant pleural mesothelioma.
- Conditions
- Malignant Pleural Mesothelioma
- Being tested
- ADI-PEG 20
- Keywords
- Pleural Mesothelioma, ADI-PEG 20
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADI-PEG 20Drug
36.8mg/m2 based on BSA, weekly treatment for 6 months
| Study group | Role | What they receive |
|---|---|---|
| A | No intervention | Arm A is control arm with best supportive care. |
| B | Experimental | Arm B is the treatment arm with best supportive care plus ADI-PEG20. Receives: Drug: ADI-PEG 20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival
Measured: 18 months
Secondary outcomes (4)
response rate
Measured: 18 months
overall survival
Measured: 18 months
time to progression
Measured: 18 months
safety (adverse events)
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionJan 2015 (estimated)
- Study completionMar 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK, UK: Barts Center for Experimental Cancer Medicine (CECM) for Trial Coordination
- Responsible party
- Sponsor
- Investigators
- Peter Szlosarek, Principal investigator, Barts and the London NHS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01279967
- Sponsor's protocol ID
- 6837
- Other IDs
- 2006-004592-35
- Acronym
- ADAM
- Status last verified
- May 2012
- First submitted
- 19 Jan 2011
- Last updated
- 20 Nov 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Szlosarek PW, Luong P, Phillips MM, Baccarini M, Stephen E, Szyszko T, Sheaff MT, Avril N. Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase. J Clin Oncol. 2013 Mar 1;31(7):e111-3. doi: 10.1200/JCO.2012.42.1784. Epub 2013 Jan 14. No abstract available.
PubMed 23319692Szlosarek PW, Steele JP, Nolan L, Gilligan D, Taylor P, Spicer J, Lind M, Mitra S, Shamash J, Phillips MM, Luong P, Payne S, Hillman P, Ellis S, Szyszko T, Dancey G, Butcher L, Beck S, Avril NE, Thomson J, Johnston A, Tomsa M, Lawrence C, Schmid P, Crook T, Wu BW, Bomalaski JS, Lemoine N, Sheaff MT, Rudd RM, Fennell D, Hackshaw A. Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1-Deficient Malignant Pleural Mesothelioma: A Randomized Clinical Trial. JAMA Oncol. 2017 Jan 1;3(1):58-66. doi: 10.1001/jamaoncol.2016.3049.
PubMed 27584578
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Stratified Multicentre Phase II Clinical Trial of Single Agent ADI-PEG 20TM (Pegylated Arginine Deiminase) in Patients With Malignant Pleural Mesothelioma
- ClinicalTrials.gov ID
- NCT01279967
- Acronym / sponsor ID
- ADAM / 6837
- Conditions
- Malignant Pleural Mesothelioma
- Keywords
- Pleural Mesothelioma, ADI-PEG 20
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Collaborators
- Cancer Research UK, UK: Barts Center for Experimental Cancer Medicine (CECM) for Trial Coordination
- Study start
- Jan 2011
- Primary completion
- Jan 2015 (estimated)
- Study completion
- Mar 2015 (estimated)
- First posted
- 20 Jan 2011 (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.
To examine whether the arginine depleting drug, ADI-PEG 20, might be effective as a targeted therapy in patients with ASS-negative malignant pleural mesothelioma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | No intervention | –Arm A is control arm with best supportive care. |
| B | Experimental | Drug: ADI-PEG 20Arm B is the treatment arm with best supportive care plus ADI-PEG20. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Males and Females aged 18 years and older. (There is no upper age limit)
- Histopathological evidence of ASS-negative MPM. All biopsies will be reviewed for ASS expression using immunohistochemistry. Central lab confirmation is required before randomization
- Performance status ECOG ≤ 1. Life expectancy should be greater than 3 months
- Chemo-naive patients OR, Patients who have been previously treated with platinum-based combination chemotherapy with progressive disease at entry. In the event of a baseline diagnostic ASS-positive test, a repeat biopsy confirming loss of ASS expression will be required post platinum-based combination chemotherapy, with at least a 4 week interval from the last treatment episode.
- CT evaluable disease by modified RECIST criteria
Key exclusion criteria (16 listed)
- Participation in another clinical trial using an investigational agent
- Patients with surgically resectable disease
- Recurrent pleural effusion (not pleurodesed)
- Receipt of extensive radiation (hemi-thorax) therapy within 6 weeks before enrollment. Radiation to chest port sites following thoracotomy is permitted
- A history of prior malignant tumour, unless the patient has been without evidence of disease for at least three years, or the tumour was a non-melanoma skin tumour or in-situ cervix carcinoma
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 |
|---|---|---|
| ADI-PEG 2036.8mg/m2 based on BSA, weekly treatment for 6 months | Drug | B |
Primary outcome
progression-free survival
Time frame: 18 months
4 secondary outcomes
response rate
Time frame: 18 months
overall survival
Time frame: 18 months
time to progression
Time frame: 18 months
safety (adverse events)
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2014.
- Background: PubMed 23319692Szlosarek PW, Luong P, Phillips MM, Baccarini M, Stephen E, Szyszko T, Sheaff MT, Avril N. Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase. J Clin Oncol. 2013 Mar 1;31(7):e111-3. doi: 10.1200/JCO.2012.42.1784. Epub 2013 Jan 14. No abstract available.
- Derived from this study: PubMed 27584578Szlosarek PW, Steele JP, Nolan L, Gilligan D, Taylor P, Spicer J, Lind M, Mitra S, Shamash J, Phillips MM, Luong P, Payne S, Hillman P, Ellis S, Szyszko T, Dancey G, Butcher L, Beck S, Avril NE, Thomson J, Johnston A, Tomsa M, Lawrence C, Schmid P, Crook T, Wu BW, Bomalaski JS, Lemoine N, Sheaff MT, Rudd RM, Fennell D, Hackshaw A. Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1-Deficient Malignant Pleural Mesothelioma: A Randomized Clinical Trial. JAMA Oncol. 2017 Jan 1;3(1):58-66. doi: 10.1001/jamaoncol.2016.3049.
- Related InfoLink provided by the sponsor.
Related trials for Malignant Pleural Mesothelioma
RecruitingPhase 1/2
Efficacy and Safety of Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy in Advanced Malignant Pleural Mesothelioma
Malignant Pleural Mesothelioma, Advanced
RecruitingPhase 2
The Diagnostic Accuracy and Clinical Value of FAPI PET in Pleural Mesothelioma
Pleural Mesothelioma, Pleural Diseases
Active, not recruitingPhase 1
Safety and Preliminary Antitumor Activity of Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy in Advanced Malignant Pleural Mesothelioma
Malignant Pleural Mesothelioma, Advanced
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1
SW-682 in Advanced Solid Tumors
Advanced Solid Tumor, Mesothelioma, Malignant
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.
Peter Szlosarek principal investigator
Barts and the London NHS
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ADI-PEG 20 in people with Malignant Pleural Mesothelioma, run by Barts & The London NHS Trust at 7 sites in United Kingdom.
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 12 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 20 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
progression-free survival (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01279967, which also lists 2 linked publications.
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 20 Nov 2014.