A Clinical Trial of ADI-PEG 20TM in Patients With Malignant Pleural Mesothelioma (ADAM)
Primary Purpose
Malignant Pleural Mesothelioma
Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
ADI-PEG 20
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring Pleural Mesothelioma, ADI-PEG 20
Eligibility Criteria
Inclusion Criteria:
- 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:
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- The Royal Sussex County Hospital
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
- Hull and East Yorkshire Hospitals NHS Trust,The Princess Royal Hospital
- Barts and The London NHS, St Bartholomew's Hospital
- Guy's and St Thomas' Foundation Trust, Guy's Hospital
- University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital
- Southampton University Hospitals NHS Trust, Southampton General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
A
B
Arm Description
Arm A is control arm with best supportive care.
Arm B is the treatment arm with best supportive care plus ADI-PEG20.
Outcomes
Primary Outcome Measures
progression-free survival
Secondary Outcome Measures
response rate
overall survival
time to progression
safety (adverse events)
Full Information
NCT ID
NCT01279967
First Posted
January 19, 2011
Last Updated
November 19, 2014
Sponsor
Barts & The London NHS Trust
Collaborators
Cancer Research UK, UK: Barts Center for Experimental Cancer Medicine (CECM) for Trial Coordination
1. Study Identification
Unique Protocol Identification Number
NCT01279967
Brief Title
A Clinical Trial of ADI-PEG 20TM in Patients With Malignant Pleural Mesothelioma
Acronym
ADAM
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Unknown status
Study Start Date
January 2011 (undefined)
Primary Completion Date
January 2015 (Anticipated)
Study Completion Date
March 2015 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Barts & The London NHS Trust
Collaborators
Cancer Research UK, UK: Barts Center for Experimental Cancer Medicine (CECM) for Trial Coordination
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma
Keywords
Pleural Mesothelioma, ADI-PEG 20
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
No Intervention
Arm Description
Arm A is control arm with best supportive care.
Arm Title
B
Arm Type
Experimental
Arm Description
Arm B is the treatment arm with best supportive care plus ADI-PEG20.
Intervention Type
Drug
Intervention Name(s)
ADI-PEG 20
Intervention Description
36.8mg/m2 based on BSA, weekly treatment for 6 months
Primary Outcome Measure Information:
Title
progression-free survival
Time Frame
18 months
Secondary Outcome Measure Information:
Title
response rate
Time Frame
18 months
Title
overall survival
Time Frame
18 months
Title
time to progression
Time Frame
18 months
Title
safety (adverse events)
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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:
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Szlosarek
Organizational Affiliation
Barts and the London NHS
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Royal Sussex County Hospital
City
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Hull and East Yorkshire Hospitals NHS Trust,The Princess Royal Hospital
City
Hull
ZIP/Postal Code
HU8 9HE
Country
United Kingdom
Facility Name
Barts and The London NHS, St Bartholomew's Hospital
City
London
ZIP/Postal Code
EC1 A 7BE
Country
United Kingdom
Facility Name
Guy's and St Thomas' Foundation Trust, Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom
Facility Name
Southampton University Hospitals NHS Trust, Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6 YD
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23319692
Citation
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.
Results Reference
background
PubMed Identifier
27584578
Citation
Szlosarek 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.
Results Reference
derived
Links:
URL
http://www.cancer.qmul.ac.uk/staff/szlosarek.html
Description
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A Clinical Trial of ADI-PEG 20TM in Patients With Malignant Pleural Mesothelioma
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