PTK787 in Patients With Advanced Metastatic Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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The purpose of this research study is to find out if an experimental drug called PTK787/ZK222584 might be effective against advanced or metastatic pancreatic cancer. In order for tumors to grow and spread to other parts of the body, they need to have a growing blood supply. Tumor cells have been shown to produce substances that stimulate the abnormal growth of new blood vessels that allow the tumor to grow. In adults, blood vessel cells normally divide very rapidly. It is thought that PTK787/ZK222584 may interfere with the growth of new blood vessels. A drug that interferes with the growth of new blood vessels might stop tumor growth, and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels. Since normal blood vessel cells divide very rarely, it might be possible to stop tumor growth without harming normal tissues.

Detailed Description
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This is an open-label, phase II multi-center therapeutic trial investigating the efficacy and tolerability of PTK787/ZK222584 in patients with metastatic or advanced pancreatic cancer who failed first line gemcitabine-based therapy. The primary objective of this study is to evaluate the 6-month survival rate, time to progression, and tolerability of the regimen in pancreatic cancer patients treated with PTK787/ZK222584 as second-line therapy.

Official Title
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Phase II Trial of PTK787/ZK222584 in Patients With Advanced or Metastatic Pancreatic Adenocarcinoma Who Failed First-Line Gemcitabine Therapy.

Conditions
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Neoplasm

Intervention / Treatment
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* Drug: PTK787/ZK222584


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 Zubrod performance status of 0 - 2 Histological or cytological diagnosis of pancreatic adenocarcinoma Measurable or evaluable disease determined as per RECIST criteria Life expectancy > 12 weeks Written informed consent Patients must have failed or progressed on prior gemcitabine-based therapy for advanced or metastatic disease. Exclusion Criteria: Islet cell or neuroendocrine carcinomas of the pancreas. History or presence of central nervous system disease. Patients with a history of another primary malignancy < 5 years Prior chemo therapy < 21 days prior to registration. Prior biologic or immunotherapy < 14 days prior to registration Prior full field radiotherapy < 28 days or limited field radiotherapy < 14 days prior to registration. Major surgery < 28 days prior to registration. Patients who have received investigational drugs < 28 days prior to registration. Prior therapy with anti-VEGF agents. Pleural effusion or ascites that causes respiratory compromise. Female patients who are pregnant or breast feeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vatalanib<br>Administered orally, twice daily: after enrollment - first week 250 BID, second week 500 BID, then 750 BID thereafter. | Drug: PTK787/ZK222584<br>* One arm: administered orally, twice daily: after enrollment - first week 250 BID, second week 500 BID, then 750 BID thereafter.<br>* Other names: bevacizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the 6-month survival rate and time to progression in pancreatic cancer patients treated with PTK787/ZK222584. | The Data Safety Monitoring Board met twice yearly while the study was active (2006-2008) to review data and each of the primary and secondary objectives. Safety Issue: the only endpoint/outcome measure that was a safety issue was the second one (safety and tolerability of PTK) | DSMC Schedule | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the response rates of patients treated with PTK787/ZK222584. | The Data Safety Monitoring Board met twice yearly while the study was active (2006-2008) to review data and each of the primary and secondary objectives. | DSMC Schedule | 
| To evaluate DCE-MRI as a surrogate of response to PTK787/ZK222584 therapy in pancreatic cancer patients. | The Data Safety Monitoring Board met twice yearly while the study was active (2006-2008) to review data and each of the primary and secondary objectives. | DSMC Schedule | 
| To perform analysis of tissue, blood and plasma markers that may be helpful in assessing the likelihood of benefit from PTK787/ZK222584 therapy. | The Data Safety Monitoring Board met twice yearly while the study was active (2006-2008) to review data and each of the primary and secondary objectives. | DSMC Schedule | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreas, adenocarcinoma, cancer, metastatic, advanced cancer, Phase II, growth factor, VEGF, angiogenesis