A Clinical Trial of ADI-PEG 20TM in Patients With Malignant Pleural Mesothelioma

Malignant Pleural Mesothelioma Clinical Trial

— 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

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01279967
• Other study ID #: 6837
• Secondary ID: 2006-004592-35
• Status: Unknown status
• Phase: Phase 2
• First received: January 19, 2011
• Last updated: November 19, 2014
• Start date: January 2011
• Est. completion date: March 2015

Study information

• Verified date: May 2012
• Source: Barts & The London NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 70
• Est. completion date: March 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males and Females aged 18 years and older. (There is no upper age limit)

2. Histopathological evidence of ASS-negative MPM. All biopsies will be reviewed for ASS expression using immunohistochemistry. Central lab confirmation is required before randomization

3. Performance status ECOG = 1. Life expectancy should be greater than 3 months

4. 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.

5. CT evaluable disease by modified RECIST criteria

6. 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.

7. Adequate hepatic function (AST and ALT < 3 x upper limit of normal; bilirubin < 1.5 x upper limit of normal)

8. Creatinine clearance >30ml/min

9. Able to give written informed consent to participate

Exclusion Criteria:

1. Participation in another clinical trial using an investigational agent

2. Patients with surgically resectable disease

3. Recurrent pleural effusion (not pleurodesed)

4. Receipt of extensive radiation (hemi-thorax) therapy within 6 weeks before enrollment. Radiation to chest port sites following thoracotomy is permitted

5. 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

6. Symptomatic or known brain or leptomeningeal metastases

7. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment

8. 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

9. Serious medical (e.g. uncontrolled diabetes, hepatic disease, infection, uncontrolled gout) or psychiatric illness likely to interfere with participation in this clinical study

10. History of seizures

11. 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

12. Females must not be breastfeeding

13. Prior exposure to ADI-PEG 20

14. Preplanned surgery or procedures that would interfere with the study protocol

15. Allergy to pegylated products

16. Exposure to another investigational drug within 4 weeks prior to start of study treatment

Related Conditions & MeSH terms

• Malignant Pleural Mesothelioma
• Mesothelioma

Intervention

Drug:
• ADI-PEG 20
36.8mg/m2 based on BSA, weekly treatment for 6 months

Locations

Country	Name	City	State
United Kingdom	The Royal Sussex County Hospital	Brighton
United Kingdom	Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital	Cambridge
United Kingdom	Hull and East Yorkshire Hospitals NHS Trust,The Princess Royal Hospital	Hull
United Kingdom	Barts and The London NHS, St Bartholomew's Hospital	London
United Kingdom	Guy's and St Thomas' Foundation Trust, Guy's Hospital	London
United Kingdom	University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital	Manchester
United Kingdom	Southampton University Hospitals NHS Trust, Southampton General Hospital	Southampton

Sponsors (3)

Lead Sponsor	Collaborator
Barts & The London NHS Trust	Cancer Research UK, UK: Barts Center for Experimental Cancer Medicine (CECM) for Trial Coordination

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival		18 months
Secondary	response rate		18 months
Secondary	overall survival		18 months
Secondary	time to progression		18 months
Secondary	safety (adverse events)		18 months

External Links

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