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

Non-Small Cell Lung Cancer and Pleural Mesothelioma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00281125
• Other study ID #: NVCI05-14
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: January 6, 2006
• Last updated: March 15, 2012
• Start date: January 2006
• Est. completion date: August 2008

Study information

• Verified date: March 2012
• Source: Nevada Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: August 2008
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Mesothelioma
• Non-Small Cell Lung Cancer and Pleural Mesothelioma

Intervention

Drug:
• PTK787 and Pemetrexed with or without Cisplatin

Locations

Country	Name	City	State
United States	Nevada Cancer Institute	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Nevada Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	To determine the pharmacokinetics of PTK787/ZK222584 in combination with Pemetrexed and Cisplatin
Secondary	To determine the pharmacokinetics of Pemetrexed in combination with PTK787/ZK 222584
Secondary	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.
Secondary	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.
Secondary	To determine the baseline expression of VEGF-R2 by immunohistochemistry in patients where paraffin blocks/slides are available.