Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma (MPM)

NCT02357147 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: MORAb-009-2012014-004489-85
• Study Type: interventional
• Target: 124
• Locations: 6 countries
• Sites: 49

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.

Conditions

Mesothelioma, Malignant

Keywords

Amatuximab; Pemetrexed; Cisplatin; Unresectable Malignant Pleural Mesothelioma; ARTEMIS

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  AEs included both non-SAEs and SAEs and the same participant can have both SAEs and as well non-SAEs.

  Baseline up to 3 years

Study Arms (2)

Arm 1

EXPERIMENTAL

Combination Phase - Amatuximab + Pemetrexed and Cisplatin Maintenance Phase - Amatuximab

Drug: Amatuximab; Drug: Pemetrexed; Drug: Cisplatin

Arm 2

EXPERIMENTAL

Combination Phase - Placebo + Pemetrexed and Cisplatin Maintenance Phase - Placebo

Drug: Placebo; Drug: Pemetrexed; Drug: Cisplatin

Interventions

Placebo DRUG

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.

Arm 2

Amatuximab DRUG

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.

Arm 1

Pemetrexed DRUG

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

Arm 1; Arm 2

Cisplatin DRUG

Combination Phase - Cisplatin 75 mg/m\^2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles.

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are at least 18 years of age at the time of informed consent
• 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
• 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
• Have other significant medical conditions well-controlled and stable in the opinion of the investigator for at least 30 days prior to Day 1
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 at Screening
• Have a life expectancy of at least 3 months, as estimated by the investigator
• 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

You may not qualify if:

• 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
• Currently have mesothelioma of the sarcomatous type, mixed histologic disease, or have malignant peritoneal mesothelioma
• Have confirmed presence of central nervous system metastases
• Active viral hepatitis or active human immunodeficiency virus infection
• 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
• 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)
• 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)
• Have known intolerance to the Test Article (ie, documented hypersensitivity AE to prior monoclonal antibody therapy, or to amatuximab or any of its excipients)
• 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
• Have any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
• Are scheduled for debulking surgery during the study
• 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
• Participants previously randomized to placebo

Sponsors & Collaborators

• Morphotek: lead

Study Sites (49)

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La Jolla, California, United States

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Newark, Delaware, United States

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Bethesda, Maryland, United States

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Rochester, Minnesota, United States

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Philadelphia, Pennsylvania, United States

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Dallas, Texas, United States

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Spokane, Washington, United States

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Camperdown, New South Wales, Australia

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Auchenflower, Queensland, Australia

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Richmond, Victoria, 3121, Australia

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Perth, Western Australia, Australia

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Caen, France

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Créteil, France

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La Tronche, France

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Lille, France

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Lyon, France

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Marseille, France

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Rennes, France

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Toulouse, France

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Berlin, Germany

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Esslingen am Neckar, Germany

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Frankfurt am Main, Germany

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Gauting, Germany

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Hamburg, Germany

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Hanover, Germany

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Löwenstein, Germany

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Ulm, Germany

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Wöhrendamm, Germany

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Rozzano, Milano, Italy

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Pisa, Paradisa 2, 56124, Italy

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Alessandria, Italy

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Aviano, Italy

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Bari, Italy

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Bergamo, Italy

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Genoa, Italy

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Genova, Italy

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Monza, Italy

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Orbassano, Italy

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Parma, Italy

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Maidstone, Kent, United Kingdom

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Dundee, United Kingdom

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Hereford, United Kingdom

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Leicester, United Kingdom

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London, United Kingdom

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Middlesex, United Kingdom

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Preston, United Kingdom

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Southampton, United Kingdom

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Swindon, United Kingdom

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Taunton, United Kingdom

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MeSH Terms

Conditions

Mesothelioma, Malignant; Severe combined immunodeficiency with sensitivity to ionizing radiation

Interventions

amatuximab; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

The study was terminated due to business decision. No safety concerns involved in decision to terminate this study.

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2015
• First Posted: February 6, 2015
• Study Start: November 3, 2015
• Primary Completion: November 30, 2018
• Study Completion: November 30, 2018
• Last Updated: March 17, 2020
• Results First Posted: March 17, 2020

Record last verified: 2017-02

Locations

US (7); IT (11); AU (4); DE (9); FR (8); GB (10)