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AMG 102, Pemetrexed Disodium, and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma

Primary Purpose

Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Recurrent Malignant Mesothelioma

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

rilotumumab

cisplatin

pemetrexed disodium

laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Advanced Malignant Mesothelioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (rilotumumab, cisplatin, pemetrexed disodium)

Arm Description

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.

Outcomes

Primary Outcome Measures

Progression-free survival

Secondary Outcome Measures

Toxicity defined as a grade 4 hemorrhagic event or a grade 5 event

Graded using the NCI CTCAE.

Full Information

NCT ID

NCT01105390

First Posted

April 15, 2010

Last Updated

August 1, 2013

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01105390

Brief Title

AMG 102, Pemetrexed Disodium, and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma

Official Title

A Phase II Trial of AMG 102 in Combination With Pemetrexed and Cisplatin in Patients With Malignant Pleural Mesothelioma

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Withdrawn

Why Stopped

withdrawn

Study Start Date

April 2010 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatous Mesothelioma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (rilotumumab, cisplatin, pemetrexed disodium)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

rilotumumab

Other Intervention Name(s)

AMG 102, anti-HGF monoclonal antibody AMG 102

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

cisplatin

Other Intervention Name(s)

CACP, CDDP, CPDD, DDP

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

pemetrexed disodium

Other Intervention Name(s)

ALIMTA, LY231514, MTA

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

Progression-free survival

Time Frame

From registration to clinical evidence of disease progression or death without progression, assessed up to 3 years

Secondary Outcome Measure Information:

Title

Toxicity defined as a grade 4 hemorrhagic event or a grade 5 event

Description

Graded using the NCI CTCAE.

Time Frame

Up to 30 days after completion of study treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James Stevenson

Organizational Affiliation

Eastern Cooperative Oncology Group

Official's Role

Principal Investigator

12. IPD Sharing Statement

Learn more about this trial

AMG 102, Pemetrexed Disodium, and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma

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