Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Pemetrexed

Cisplatin

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Combination Phase - Amatuximab + Pemetrexed and Cisplatin

Maintenance Phase - Amatuximab

Combination Phase - Placebo + Pemetrexed and Cisplatin

Maintenance Phase - 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.

Placebo

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.

Amatuximab

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

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

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.

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

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

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

Morphotek

Deaths that happened anytime during the study (including those during the treatment and after treatment discontinuation) are reported in this section.

During Combination Treatment Phase, participants received amatuximab 5 mg/kg, infusion, intravenously, once weekly in 21-day cycles and pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2, infusion, intravenously, on Day 1 of each 21-day cycle for 6 cycles.

Combination Treatment Phase:Amatuximab + Pemetrexed +Cisplatin

During Combination Treatment Phase, participants received placebo matched to amatuximab infusion, intravenously, once weekly in 21-day cycles and pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2, infusion, intravenously, on Day 1 of each 21-day cycle for 6 cycles.

Combination Treatment Phase: Placebo + Pemetrexed + Cisplatin

Following completion of the Combination Treatment Phase, participants who had not progressed entered the Maintenance Phase and continued to receive amatuximab 5 mg/kg, infusion, intravenously, once weekly until disease progression.

Maintenance Treatment Phase: Amatuximab

Following completion of the Combination Treatment Phase, participants who had not progressed entered the Maintenance Phase and received placebo matched to amatuximab infusion, intravenously, once weekly until disease progression.

Maintenance Treatment Phase: Placebo

During Combination Treatment Phase, participants received amatuximab 5 mg/kg, infusion, intravenously, once weekly in 21-day cycles and pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2, infusion, intravenously, on Day 1 of each 21-day cycle for 6 cycles. Following completion of the Combination Treatment Phase, participants who had not progressed entered the Maintenance Phase and continued to receive amatuximab 5 mg/kg, infusion, intravenously, once weekly until disease progression.

Amatuximab + Pemetrexed + Cisplatin

During Combination Treatment Phase, participants received placebo matched to amatuximab infusion, intravenously, once weekly in 21-day cycles and pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2, infusion, intravenously, on Day 1 of each 21-day cycle for 6 cycles. Following completion of the Combination Treatment Phase, participants who had not progressed entered the Maintenance Phase and received placebo matched to amatuximab infusion, intravenously, once weekly until disease progression.

Placebo + Pemetrexed + Cisplatin

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The safety analysis set was defined as all randomized participants who received at least 1 dose of study drug.

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

Eisai Medical Information

SAEs

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

During Combination Treatment Phase, participants received amatuximab 5 milligram per kilogram (mg/kg), infusion, intravenously, once weekly in 21-day cycles and pemetrexed 500 milligram per square meter (mg/m\^2) and cisplatin 75 mg/m\^2, infusion, intravenously, on Day 1 of each 21-day cycle for 6 cycles. Following completion of the Combination Treatment Phase, participants who had not progressed entered the Maintenance Phase and continued to receive amatuximab 5 mg/kg, infusion, intravenously, once weekly until disease progression.

Combination Treatment Phase

Maintenance Treatment Phase

Alisertib administered by mouth at 50 mg twice a day for 7 days in each treatment cycle, followed by a 14-day, treatment-free period.

50 mg twice a day on Days 1-7 of each 21-day study cycle.

Alisertib

Anne S. Tsao, MD

Objectives:

Objectives

The primary objective of this study is to:

To assess 4-month disease control rate (DCR) in pre-treated patients with unresectable malignant pleural mesothelioma (MPM) treated with alisertib

The secondary objectives of this study are to:

To assess the response rate (confirmed and unconfirmed complete + partial responses) To assess the progression-free survival. To assess overall survival. To evaluate the side effects and toxicities associated with this treatment regimen.

To collect archival tissue, blood, pleural effusion fluid and plasma for correlative studies.

Exploratory Objectives:

To collect archival or new tissue, blood and pleural effusion fluid for correlative studies. Tissue biomarkers to be evaluated include aurora kinase pathway and c-myc gene amplification.

Next generation sequencing (NGS) will be conducted on adequate tumor tissue specimens.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take alisertib tablets by mouth 2 times each day on Days 1-7 of each 21-day study cycle. You must take your doses of alisertib at least 6 hours apart with 1 cup (about 8 ounces) of water.

If you miss or vomit a dose of alisertib, do not retake that dose. Wait and take the next dose as scheduled.

Study Visits:

On Day 1 of Cycles 1-3 and then every odd-numbered cycle after that (Cycles 5, 7, 9 and so on):

* You will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests.

Every 6 weeks while you are on study, you will have a PET-CT scan of your chest, abdomen, and pelvis to check the status of the disease.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on this study will be over after you have completed follow-up.

Follow up:

Your study doctor or study team will follow you up 30 days after your last dose by reviewing your medical chart or calling you to see if the side effects are resolved. After that, you will continue to be followed up at 3 months, 6 months and every 6 months beyond that.

The study doctor can explain how the study drug is designed to work.

Up to 58 participants will be enrolled in this study. All will take part at MD Anderson.

Phase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma

Patients who are free of disease progression at 4 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Overall Survival is defined as the time from the date of randomization to the date of death due to any cause.

PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease (PD) or date of death, whichever occurs first. Progression is defined using modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions or RECIST 1.1 if mRECIST cannot be used.

Millennium Pharmaceuticals, Inc.

M.D. Anderson Cancer Center

Alisertib was administered PO at 50 mg BID for 7 days in each treatment cycle, followed by a 14-day, treatment-free period, for a 21-day cycle.

Age, Categorical

United States

Region of Enrollment

Number of Participants with Prior Systemic Therapies

Dr. Anne Tsao, MD- VP, Academic Affairs, CAO Office

1 patient did not complete one cycle of treatment and 25 patients were evaluable for efficacy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma (MPM)	NCT02357147	Mesothelioma, M...	Placebo Amatuximab Pemetrexed Cisplatin	18 Years -	Morphotek
Phase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma	NCT02293005	Lung Cancer Mesothelioma	Alisertib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for unresectable malignant pleural mesothelioma