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

NCT ID: NCT02357147

Last Updated: 2020-03-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-03
• Study Completion Date: 2018-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm 1

Combination Phase - Amatuximab + Pemetrexed and Cisplatin

Maintenance Phase - Amatuximab

Group Type: EXPERIMENTAL

Amatuximab

Intervention Type: 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.

Pemetrexed

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Arm 2

Combination Phase - Placebo + Pemetrexed and Cisplatin

Maintenance Phase - Placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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.

Pemetrexed

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Pemetrexed

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Morphotek

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

La Jolla, California, United States

Newark, Delaware, United States

Bethesda, Maryland, United States

Rochester, Minnesota, United States

Philadelphia, Pennsylvania, United States

Dallas, Texas, United States

Spokane, Washington, United States

Camperdown, New South Wales, Australia

Auchenflower, Queensland, Australia

Richmond, Victoria, Australia

Perth, Western Australia, Australia

Caen, , France

Créteil, , France

La Tronche, , France

Lille, , France

Lyon, , France

Marseille, , France

Rennes, , France

Toulouse, , France

Berlin, , Germany

Esslingen am Neckar, , Germany

Frankfurt am Main, , Germany

Gauting, , Germany

Hamburg, , Germany

Hanover, , Germany

Löwenstein, , Germany

Ulm, , Germany

Wöhrendamm, , Germany

Rozzano, Milano, Italy

Pisa, Paradisa 2, Italy

Alessandria, , Italy

Aviano, , Italy

Bari, , Italy

Bergamo, , Italy

Genoa, , Italy

Genova, , Italy

Monza, , Italy

Orbassano, , Italy

Parma, , Italy

Maidstone, Kent, United Kingdom

Dundee, , United Kingdom

Hereford, , United Kingdom

Leicester, , United Kingdom

London, , United Kingdom

Middlesex, , United Kingdom

Preston, , United Kingdom

Southampton, , United Kingdom

Swindon, , United Kingdom

Taunton, , United Kingdom

Countries

United States; Australia; France; Germany; Italy; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-004489-85

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MORAb-009-201

Identifier Type: -

Identifier Source: org_study_id