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

Purpose

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.

Condition	Intervention	Phase
Non-Small Cell Lung Cancer and Pleural Mesothelioma	Drug: PTK787 and Pemetrexed with or without Cisplatin	Phase I Phase II

MedlinePlus related topics:

Cancer Lung Cancer Mesothelioma

ChemIDplus related topics:

Cisplatin Pemetrexed disodium Pemetrexed Vatalanib Butanedioic acid, compd. with N-(4-chlorophenyl)-4-(4-pyridinylmethyl)-1-phthalazinamine (1:1)

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study

Official Title:	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

Further study details as provided by Nevada Cancer Institute:

Primary Outcome Measures:

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:

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.

Estimated Enrollment:	20
Study Start Date:	January 2006
Estimated Study Completion Date:	September 2006

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281125

Locations


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

Sponsors and Collaborators

Nevada Cancer Institute

Investigators


Principal Investigator:	Sunil Sharma, MD	Nevada Cancer Institute

More Information

Study ID Numbers:	NVCI05-14
First Received:	January 6, 2006
Last Updated:	September 6, 2006
ClinicalTrials.gov Identifier:	NCT00281125
Health Authority:	United States: Food and Drug Administration

Keywords provided by Nevada Cancer Institute:

Non-Small Cell Lung Cancer

Pleural Mesothelioma

Study placed in the following topic categories:

Thoracic Neoplasms

Non-small cell lung cancer

Carcinoma

Vatalanib

Folic Acid

Pemetrexed

Respiratory Tract Diseases

Cisplatin

Lung Neoplasms

Lung Diseases

Mesothelioma

Carcinoma, Non-Small-Cell Lung

Adenoma

Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites

Respiratory Tract Neoplasms

Antimetabolites, Antineoplastic

Neoplasms by Histologic Type

Molecular Mechanisms of Pharmacological Action

Neoplasms, Mesothelial

Antineoplastic Agents

Physiological Effects of Drugs

Enzyme Inhibitors

Folic Acid Antagonists

Protein Kinase Inhibitors

Pharmacologic Actions

Neoplasms

Neoplasms by Site

Radiation-Sensitizing Agents

Therapeutic Uses

ClinicalTrials.gov processed this record on September 04, 2008

Sponsored by:	Nevada Cancer Institute
Information provided by:	Nevada Cancer Institute
ClinicalTrials.gov Identifier:	NCT00281125