AMG 102, Pemetrexed Disodium, and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma - Full Text View

Purpose

This phase II trial is studying how well giving AMG 102 together with pemetrexed disodium and cisplatin works in treating patients with malignant pleural mesothelioma. Monoclonal antibodies, such as AMG 102, can block tumor growth in different ways. Some block the ability of tumor cells to grow or spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AMG 102 together with pemetrexed disodium and cisplatin may kill more tumor cells

Condition	Intervention	Phase
Advanced Malignant Mesothelioma Epithelial Mesothelioma Recurrent Malignant Mesothelioma Sarcomatous Mesothelioma	Biological: rilotumumab Drug: cisplatin Drug: pemetrexed disodium Other: laboratory biomarker analysis	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Trial of AMG 102 in Combination With Pemetrexed and Cisplatin in Patients With Malignant Pleural Mesothelioma

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Mesothelioma

Drug Information available for: Cisplatin Pemetrexed Pemetrexed disodium

Genetic and Rare Diseases Information Center resources: Malignant Mesothelioma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival [ Time Frame: From registration to clinical evidence of disease progression or death without progression, assessed up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity defined as a grade 4 hemorrhagic event or a grade 5 event [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
Graded using the NCI CTCAE.


Enrollment:	0
Study Start Date:	April 2010
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (rilotumumab, cisplatin, pemetrexed disodium) Patients receive anti-HGF monoclonal antibody AMG 102 (AMG 102) IV over 1 hour, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients without disease progression may continue AMG 102 IV over 1 hour on day 1, every 3 weeks, as maintenance therapy in the absence of disease progression.	Biological: rilotumumab Given IV Other Names: AMG 102 anti-HGF monoclonal antibody AMG 102 Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Drug: pemetrexed disodium Given IV Other Names: ALIMTA LY231514 MTA Other: laboratory biomarker analysis Correlative studies

Arms

Assigned Interventions

Experimental: Treatment (rilotumumab, cisplatin, pemetrexed disodium)

Patients receive anti-HGF monoclonal antibody AMG 102 (AMG 102) IV over 1 hour, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients without disease progression may continue AMG 102 IV over 1 hour on day 1, every 3 weeks, as maintenance therapy in the absence of disease progression.

Biological: rilotumumab

Given IV

Other Names:

AMG 102
anti-HGF monoclonal antibody AMG 102

Drug: cisplatin

Given IV

Other Names:

CACP
CDDP
CPDD
DDP

Drug: pemetrexed disodium

Given IV

Other Names:

ALIMTA
LY231514
MTA

Other: laboratory biomarker analysis

Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival of patients with malignant pleural mesothelioma (MPM) treated with anti-HGF monoclonal antibody AMG 102 in combination with pemetrexed disodium and cisplatin.

SECONDARY OBJECTIVES:

I. To assess the toxicity associated with this regimen in these patients. II. To determine the response rate of patients treated with this regimen. III. To determine the overall survival of patients treated with this regimen. IV. To evaluate multiple potential correlative biomarkers in MPM that are relevant to this combined regimen, including serum HGF and mesothelin levels, c-met expression by IHC in tumor specimens, presence of c-met mutations in tumor, and the presence of thymidylate synthetase (TS) and excision repair cross complementing protein-1 (ERCC1) polymorphisms.

OUTLINE: This is a multicenter study.

Patients receive anti-HGF monoclonal antibody AMG 102 (AMG 102) IV over 1 hour, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients without disease progression may continue AMG 102 IV over 1 hour on day 1, every 3 weeks, as maintenance therapy in the absence of disease progression. Some patients undergo blood sample collection at baseline and periodically during study for correlative biomarker studies. Tumor samples from diagnostic tissue may also be analyzed.

After completion of study therapy, patients are followed up periodically every 3 months for 2 years and then every 6 months for 1 year.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically and cytologically confirmed malignant mesothelioma of the pleura
- All subtypes allowed
- Disease not amenable to curative surgery
Measurable disease
- Patients with disease not measurable by standard RECIST criteria (i.e., pleural rinds/thickening only) allowed
- Pleural effusions or positive bone scans are not considered measurable
No prior radiotherapy to the target lesion or measurable lesion unless the site has subsequent evidence of progression
Patients who have undergone pleurodesis allowed
- Post-pleurodesis CT scan required
No known or suspected brain metastases
ECOG performance status 0-1
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 1.5 times ULN
ALT and AST ≤ 1.5 times ULN
Albumin ≥ 2.5 g/dL
Creatinine clearance ≥ 45 mL/min OR serum creatinine ≤ 1.5 times ULN
Able to take folic acid and vitamin B12
Not pregnant or nursing
Negative pregnancy test
Fertile patients must agree to use effective contraception
No active infection or serious concomitant systemic disorder in compatible with the study
No thrombosis or vascular ischemic events within the last 12 months, including any of the following:
- Deep venous thrombosis
- Pulmonary embolism
- Transient ischemic attack
- Cerebral infarction
- Myocardial infarction
No peripheral edema ≥ grade 3
No serious or non-healing wounds
No second primary malignancy except in situ carcinoma of the cervix or breast, other in situ malignancies, adequately treated basal cell carcinoma of the skin, or other malignancy within the past 3 years with no evidence of recurrence
No concurrent antiretroviral therapy for HIV-positive patients
At least 4 weeks since prior radiotherapy
More than 30 days since major surgery procedures or > 14 days since any minor surgical procedure and recovered
- Central venous catheter placement, fine-needle aspiration, thoracentesis, or paracentesis are not considered major or minor surgical procedures
No prior systemic chemotherapy for mesothelioma
No prior intracavity cytotoxic drugs or immunomodulators (unless for the purpose of pleurodesis)
No prior anti-HGF monoclonal antibody AMG 102, other c-MET, or HGF inhibitors
No prior or concurrent anticoagulation therapy within the past 7 days
- Low-dose Coumadin-type anticoagulants or low-molecular weight heparin for prophylaxis against central venous catheter thrombosis allowed
No investigational agents within the past 4 weeks

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01105390

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	James Stevenson	Eastern Cooperative Oncology Group

More Information


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01105390 History of Changes
Other Study ID Numbers:	E1B09 NCI-2011-02068 U10CA021115 CDR0000670445
Study First Received:	April 15, 2010
Last Updated:	August 1, 2013
Health Authority:	United States: Institutional Review Board United States: Federal Government

Additional relevant MeSH terms:


Mesothelioma Lung Neoplasms Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Mesothelial Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases	Cisplatin Pemetrexed Antibodies Antibodies, Monoclonal Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 27, 2016