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

This study has been terminated.
(Suspended due to data issues revealed at DSMB meeting. Planned amendment but was never submitted. Study was then closed.)
Sponsor:
Information provided by:
Nevada Cancer Institute
ClinicalTrials.gov Identifier:
NCT00281125
First received: January 6, 2006
Last updated: March 15, 2012
Last verified: March 2012
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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
Study Completion Date: August 2008
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
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
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: 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

ClinicalTrials.gov Identifier: NCT00281125     History of Changes
Other Study ID Numbers: NVCI05-14
Study First Received: January 6, 2006
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Nevada Cancer Institute:
Non-Small Cell Lung Cancer
Pleural Mesothelioma

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

ClinicalTrials.gov processed this record on August 28, 2014