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
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.
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.
- 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
- 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.
- 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
- 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
- Pregnant and nursing women are excluded from this study
- Patients who had any major surgery within 4 weeks