Phase I/II Trial of PTK787 and Pemetrexed With or Without Cisplatin for Lung Cancer

A Two-Cohort Phase I/II Trial of PTK787 and Pemetrexed With or Without Cisplatin in Patients With Advanced Non-Small Cell Lung Cancers and Malignant Pleural Mesotheliomas

This is an open-label, two-arm, multicenter Phase IA/II dose-escalation study of PTK787 in combination with Pemetrexed alone (Cohort 1) or Pemetrexed and Cisplatin (Cohort 2).

This study is designed to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of PTK787 when administered in combination with Pemetrexed or Pemetrexed and Cisplatin, and to characterize the safety, tolerability, biologic activity, and PK profile of PTK787 in adult patients with advanced non-small cell lung cancers and mesotheliomas.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer and Pleural Mesothelioma
• Intervention / Treatment: Drug: PTK787 and Pemetrexed with or without Cisplatin

Detailed Description

This is an open-label, two-arm, multicenter Phase IA/II dose-escalation study of PTK787 in combination with Pemetrexed alone (Cohort 1) or Pemetrexed and Cisplatin (Cohort 2).

This study is designed to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of PTK787 when administered in combination with Pemetrexed or Pemetrexed and Cisplatin, and to characterize the safety, tolerability, biologic activity, and PK profile of PTK787 in adult patients with advanced non-small cell lung cancers and mesotheliomas.

In cohort 1, PTK787 will be administered orally every 12 hours on days 2-42 of a 42-day cycle. In addition, Pemetrexed will be administered on days 1 and 22.

In cohort 2, PTK787 will be administered orally every 12 hours on days 2-42 of a 42 day cycle. In addition, Pemetrexed will be administered on days 1 and 22. Thirty minutes after Pemetrexed administration, Cisplatin will be infused on days 1 and 22.

In the current study, initially patients will be treated on Cohort 1 (Pemetrexed + PTK787). Once an MTD determination is made on this cohort (or PTK787 has been escalated to the maximum dose of 750 mg Q12h enrollment will begin on Cohort 2. At the MTD dose, both cohorts will be expanded to a minimum of 20 patients to determine additional safety of the combinations.

• Study Type: Interventional
• Enrollment: 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Nevada Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with advanced non-small cell lung cancers (non-squamous variety and advanced mesotheliomas
• Patients with advanced solid tumors who are refractory to standard treatments and/or standard treatments are not be available for the patient

Exclusion Criteria:

• Non-small cell carcinoma of squamous variety
• Patients with uncontrolled brain metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To determine the Maximum tolerated dose (MTD) and Dose Limiting toxicities (DLTs) of a combination of Pemetrexed and PTK787/ZK222584 (Cohort 1) and a combination of Pemetrexed with Cisplatin and PTK787/ZK222584 (Cohort 2) in patients

Secondary Outcome Measures

Outcome Measure
To determine the preliminary evidence of safety of the above combinations in patients with non-small cell lung cancers and/or mesotheliomas (in the expansion cohorts)
To determine the pharmacokinetics of PTK787/ZK222584 in combination with Pemetrexed and Cisplatin
To determine the pharmacokinetics of Pemetrexed in combination with PTK787/ZK 222584
To determine the effect of therapy with the combination on plasma levels of VEGF A, B, C and D and on plasma levels of soluble VEGF-R2.
To determine the relationship between PTK787/ZK 222584 and Pemetrexed pharmacokinetics and plasma levels of VEGF A, B, C, D, soluble VEGF-R2, and exploratory chemotherapeutic response biomarkers.
To determine the baseline expression of VEGF-R2 by immunohistochemistry in patients where paraffin blocks/slides are available.

Collaborators and Investigators

• Sponsor: Nevada Cancer Institute
• Investigators: Principal Investigator: Sunil Sharma, MD, Nevada Cancer Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: January 6, 2006
• First Submitted That Met QC Criteria: January 20, 2006
• First Posted (Estimate): January 24, 2006

Study Record Updates

• Last Update Posted (Estimate): March 19, 2012
• Last Update Submitted That Met QC Criteria: March 15, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Pleural Mesothelioma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Mesothelioma; Mesothelioma, Malignant; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Pemetrexed; Vatalanib
• Other Study ID Numbers: NVCI05-14