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

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

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

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Mesothelioma

Drug Information available for: Cisplatin Pemetrexed Pemetrexed disodium Vatalanib

U.S. FDA Resources

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

No publications provided

Study ID Numbers:	NVCI05-14
Study First Received:	January 6, 2006
Last Updated:	September 6, 2006
ClinicalTrials.gov Identifier:	NCT00281125 History of Changes
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:

Antimetabolites
Thoracic Neoplasms
Folate
Folinic Acid
Folic Acid Antagonists
Protein Kinase Inhibitors
Vitamin B9
Carcinoma
Vatalanib
Folic Acid
Pemetrexed

Radiation-Sensitizing Agents
Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Lung Diseases
Mesothelioma
Non-small Cell Lung Cancer
Carcinoma, Non-Small-Cell Lung
Adenoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Thoracic Neoplasms
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Neoplasms, Mesothelial
Antineoplastic Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Vatalanib
Neoplasms by Site
Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Therapeutic Uses

Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Enzyme Inhibitors
Folic Acid Antagonists
Pharmacologic Actions
Carcinoma
Pemetrexed
Neoplasms
Radiation-Sensitizing Agents
Lung Diseases
Mesothelioma
Adenoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on July 02, 2009