A Study of VEGF-Antisense Oligonucleotide in Combination With Pemetrexed and Cisplatin for the Treatment of Advanced Malignant Mesothelioma

This study has been withdrawn prior to enrollment.
(Sponsor withdrew support)
Sponsor:
Collaborator:
Sponsor Name Pending
Information provided by:
University of Southern California
ClinicalTrials.gov Identifier:
NCT00668499
First received: April 25, 2008
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

This will be a single institution non-randomized phase I/II trial for patients with malignant mesothelioma stage II and above, who have not received prior chemotherapy for their disease.

The purpose of this phase is to select a dose of VEGF-AS (antiangiogenesis drug)to be given with standard doses of pemetrexed followed by cisplatin on day 1 of a 21-day cycle.


Condition Intervention Phase
Mesothelioma
Drug: VEGF-Antisense Oligonucleotide , Pemetrexed, Cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of VEGF-Antisense Oligonucleotide (VEGF-AS, Veglin) in Combination With Pemetrexed and Cisplatin for the Treatment of Advanced Malignant Mesothelioma

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • The primary endpoint of the phase II trial will be time to progression [ Time Frame: Tumor measurements every 6 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary endpoints are objective response rate and overall survival [ Time Frame: Every 6 weeks evaluations ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: April 2008
Estimated Study Completion Date: April 2011
Estimated Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: VEGF-Antisense Oligonucleotide , Pemetrexed, Cisplatin
    VEGF-AS either 100 or 200mg/m2 IV days 1-5, Pemetrexed 500mg/m2 and Cisplatin 75mg/m2 IV on day 1. Cycle repeated every 3 weeks until 6 cycles completed, unless PD or toxicities
Detailed Description:

The Study Objectives in Phase I are:

To determine the safety of the combination of VEGF-Antisense Oligonucleotide (VEGF-AS, Veglin™) plus Pemetrexed and Cisplatin in subjects with advanced Malignant Mesothelioma,.via a dose escalation protocol. To determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of VEGF-AS plus Premetrexed and Cisplatin. To determine the time to disease progression To determine the objective response rate of the combination of VEGF-AS plus Pemetrexed and Cisplatin for the treatment of advanced malignant mesothelioma

The study Objectives in Phase II are:

To further characterize the toxicity experienced by patients with malignant mesothelioma treated with VEGF-AS plus Cisplatin and Pemetrexed.

To determine median and overall survival.

The Laboratory objectives are:

To measure plasma VEGF levels before, during, and after therapy as a correlate of outcome. To determine the pharmacokinetic profile of VEGF-AS plus Pemetrexed and Cisplatin.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed malignant pleural mesothelioma, epithelial, sarcomatoid, or mixed subtype
  • Patients must have measurable disease,using RECIST criteria.Pleural effusions and ascites are not considered measurable lesions.
  • Patients with pleural mesothelioma must be IMIG stage ≥II
  • Age greater than or equal to 18 years.
  • ECOG performance status less than or equal to 2 and an estimated survival of at least 3 months
  • Patients must have adequate organ and marrow function as defined below:

Absolute neutrophil count greater than or equal to1,500 Platelets greater than or equal to 100,000 Total bilirubin less than or equal to2.0x the upper limits of institutional normal AST/ALT less than or equal to 2.0x the upper limits of institutional normal Creatinine Clearance greater than 50ml/min

  • The effects of VEGF-AS on the developing human fetus are unknown.
  • Pemetrexed may cause fetal harm when administered to a pregnant woman and is classified pregnancy category D. There are no studies of pemetrexed in pregnant women. Cisplatin is also categorized as FDA Pregnancy Category D. There is positive evidence of human fetal risk. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent.
  • Patients with history of prior cured malignancy > 5 years since the completion of treatment may be accrued provided that other eligibility criteria are met.

Exclusion Criteria:

  • Patients who have had chemotherapy for Mesothelioma prior to study entry
  • Patients who have had radiation therapy within 3 weeks prior to entering the study. All patients should have recovered from all toxicities of prior therapy.
  • Patients receiving therapy with other investigational agents at the time of study enrollment.
  • Patients with uncontrolled brain metastases
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and nursing women are excluded from this study
  • Patients who had any major surgery within 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: NCT00668499

Locations
United States, California
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
Sponsor Name Pending
Investigators
Principal Investigator: Barbara Gitlitz, MD University of Southern California
  More Information

No publications provided

Responsible Party: Dr. Barbara Gitlitz, University of Southern California
ClinicalTrials.gov Identifier: NCT00668499     History of Changes
Other Study ID Numbers: 18M-07-2
Study First Received: April 25, 2008
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Lung Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on August 19, 2014