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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02357147




Registration number
NCT02357147
Ethics application status
Date submitted
14/01/2015
Date registered
6/02/2015
Date last updated
17/03/2020

Titles & IDs
Public title
Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma (MPM)
Scientific title
A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma
Secondary ID [1] 0 0
2014-004489-85
Secondary ID [2] 0 0
MORAb-009-201
Universal Trial Number (UTN)
Trial acronym
ARTEMIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mesothelioma, Malignant 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Amatuximab
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Cisplatin

Experimental: Arm 1 - Combination Phase - Amatuximab + Pemetrexed and Cisplatin

Maintenance Phase - Amatuximab

Experimental: Arm 2 - Combination Phase - Placebo + Pemetrexed and Cisplatin

Maintenance Phase - Placebo


Treatment: Drugs: Placebo
Combination Phase - Placebo will be administered IV (intravenous infusion) once weekly for six 21-day cycles.

Maintenance Phase - Placebo will be administered IV (intravenous infusion) once weekly until disease progression.

Treatment: Drugs: Amatuximab
Combination Phase - Amatuximab 5mg/kg will be administered IV (intravenous infusion) once weekly for six 21-day cycles.

Maintenance Phase - Amatuximab 5mg/kg will be administered IV (intravenous infusion) once weekly until disease progression.

Treatment: Drugs: Pemetrexed
Combination Phase - Pemetrexed 500 mg/m\^2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles.

Treatment: Drugs: Cisplatin
Combination Phase - Cisplatin 75 mg/m\^2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Baseline up to 3 years

Eligibility
Key inclusion criteria
1. Are at least 18 years of age at the time of informed consent
2. Have confirmed diagnosis of MPM with the following characteristics:

* Unresectable disease (defined as the participant not being a candidate for curative surgery)
* Epithelial type
* Have an archived tissue sample to be submitted either as a formalin fixed paraffin-embedded (FFPE) tumor block, or 5 to 15 unstained slides
3. Have measurable disease at Screening by computed tomography (CT) (or magnetic resonance imaging [MRI]) as defined by at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to the modified RECIST criteria
4. Have other significant medical conditions well-controlled and stable in the opinion of the investigator for at least 30 days prior to Day 1
5. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 at Screening
6. Have a life expectancy of at least 3 months, as estimated by the investigator
7. Have adequate organ reserve as determined by laboratory test results obtained within 2 weeks prior to Study Day 1 as indicated below:

* Absolute neutrophil count greater than or equal to 1.5 x 10^9/L
* Platelet count greater than or equal to 100 x 10^9/L
* Hemoglobin greater than or equal to 9 g/dL
* Serum bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (Participants with serum bilirubin abnormalities greater than this specified limit are eligible only if they have known Gilberts disease)
* Aspartate aminotransferase less than or equal to 3 x ULN
* Alanine aminotransferase less than or equal to 3 x ULN
* Alkaline phosphatase less than or equal to 3 x ULN
8. Have a calculated serum creatinine clearance greater than or equal to 45 mL/min using the Cockcroft-Gault equation
9. Participants of childbearing potential must be surgically sterile or consent to use a highly effective method of contraception throughout the study period. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). If a participant of childbearing potential is neither surgically sterile nor postmenopausal, highly effective contraceptive measures must start either prior to or at Screening and continue throughout the entire study period and for at least 6 months after the last dose of chemotherapy and at least 30 days after the last dose of Test Article (amatuximab or placebo) is administered (whichever is later). A highly effective method of contraception is defined as one that results in a low failure rate (that is, less than 1% per year) when used consistently and correctly. Periodic abstinence, the rhythm method, the withdrawal method, condoms, and diaphragms are not acceptable methods of contraception. Women of childbearing potential must also refrain from egg cell donation for 6 months after the final dose of investigational product
10. Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 6 months after discontinuation of chemotherapy and for 5 weeks after Test Article (amatuximab or placebo) discontinuation (whichever is later). No sperm donation is allowed during the study period and for 90 days after Test Article discontinuation
11. Be willing and able to provide written informed consent
12. Be willing and able to comply with all aspects of the protocol
13. Participants who were enrolled in the study and randomized to the amatuximab treatment arm may, at the discretion of the principle investigator (PI), consent to continue to receive amatuximab therapy until disease progression, intolerable toxicity, or withdraw of consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have any history of the following:

* Prior systemic therapy or radiotherapy for MPM; local radiotherapy of noncurative intent (ie, for prevention of instrument-tract recurrence and/or symptom control) is permitted
* Evidence of other active, invasive malignancy requiring treatment within the past 5 years; noninvasive cancer history (such as carcinoma-in-situ [CIS] that has been resected) is allowed
2. Currently have mesothelioma of the sarcomatous type, mixed histologic disease, or have malignant peritoneal mesothelioma
3. Have confirmed presence of central nervous system metastases
4. Active viral hepatitis or active human immunodeficiency virus infection
5. Have evidence of any other serious systemic disease, including active bacterial or fungal infection, or any medical condition that, in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
6. Clinically significant heart disease (eg, congestive heart failure of New York Heart Association Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 months)
7. Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: participants with chronic atrial arrhythmia, ie, atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible). A clinically significant ECG abnormality, including a marked prolonged QT/QTc interval (eg, a repeated demonstration of a QTc interval of greater than 500 ms)
8. Have known intolerance to the Test Article (ie, documented hypersensitivity AE to prior monoclonal antibody therapy, or to amatuximab or any of its excipients)
9. Pregnant and/or lactating females are excluded; a negative beta-human chorionic gonadotropin [B-hCG]) is required during Screening, and a separate local assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of Test Article
10. Have any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
11. Are scheduled for debulking surgery during the study
12. Are currently enrolled in another clinical study or used any investigational drug or device within 30 days (or 5 x the half-life of the investigational drug/device, whichever is longer) preceding informed consent
13. Participants previously randomized to placebo
14. Participants who have not signed the updated informed consent form associated with this amendment 2
15. Participants who have radiographic or clinical disease progression or intolerable toxicity such that ongoing amatuximab treatment through this study is not appropriate

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2018
Sample size
Target
Accrual to date
Final
124
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Auchenflower
Recruitment hospital [3] 0 0
- Richmond
Recruitment hospital [4] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Auchenflower
Recruitment postcode(s) [3] 0 0
3121 - Richmond
Recruitment postcode(s) [4] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Delaware
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
France
State/province [8] 0 0
Caen
Country [9] 0 0
France
State/province [9] 0 0
Creteil
Country [10] 0 0
France
State/province [10] 0 0
La Tronche
Country [11] 0 0
France
State/province [11] 0 0
Lille
Country [12] 0 0
France
State/province [12] 0 0
Lyon Cedex
Country [13] 0 0
France
State/province [13] 0 0
Marseille
Country [14] 0 0
France
State/province [14] 0 0
Rennes
Country [15] 0 0
France
State/province [15] 0 0
Toulouse
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Esslingen
Country [18] 0 0
Germany
State/province [18] 0 0
Frankfurt am Main
Country [19] 0 0
Germany
State/province [19] 0 0
Gauting
Country [20] 0 0
Germany
State/province [20] 0 0
Hamburg
Country [21] 0 0
Germany
State/province [21] 0 0
Hanover
Country [22] 0 0
Germany
State/province [22] 0 0
Löwenstein
Country [23] 0 0
Germany
State/province [23] 0 0
Ulm
Country [24] 0 0
Germany
State/province [24] 0 0
Wöhrendamm
Country [25] 0 0
Italy
State/province [25] 0 0
Milano
Country [26] 0 0
Italy
State/province [26] 0 0
Paradisa 2
Country [27] 0 0
Italy
State/province [27] 0 0
Alessandria
Country [28] 0 0
Italy
State/province [28] 0 0
Aviano
Country [29] 0 0
Italy
State/province [29] 0 0
Bari
Country [30] 0 0
Italy
State/province [30] 0 0
Bergamo
Country [31] 0 0
Italy
State/province [31] 0 0
Genoa
Country [32] 0 0
Italy
State/province [32] 0 0
Genova
Country [33] 0 0
Italy
State/province [33] 0 0
Monza
Country [34] 0 0
Italy
State/province [34] 0 0
Orbassano
Country [35] 0 0
Italy
State/province [35] 0 0
Parma
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Kent
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Dundee
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Hereford
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Leicester
Country [40] 0 0
United Kingdom
State/province [40] 0 0
London
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Middlesex
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Preston
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Southampton
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Swindon
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Taunton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Morphotek
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study was originally designed as a multicenter, double-blind, randomized, parallel-group study, using a placebo control or amatuximab 5 milligrams per kilogram (mg/kg), administered weekly, designed to evaluate the safety and efficacy of amatuximab in combination with pemetrexed and cisplatin in participants with unresectable Malignant Pleural Mesothelioma (MPM) who have not received prior systemic therapy.

Per a business decision made by the Sponsor, participants who were randomized to amatuximab and were still on active treatment at the time of the protocol amendment may have consented to continue to receive weekly treatment with amatuximab until disease progression or intolerable toxicity at the discretion of the principal investigator. Participants randomized to placebo or who were in follow-up at the time of the amendment have been discontinued from the study.
Trial website
https://clinicaltrials.gov/study/NCT02357147
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02357147