Phase I/II PTK787/ZK 222584 and Gemcitabine in Advanced Pancreatic Cancer

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
George Albert Fisher, Stanford University
ClinicalTrials.gov Identifier:
NCT00185588
First received: September 12, 2005
Last updated: November 6, 2012
Last verified: October 2011
  Purpose

The purpose of the study is to determine the optimal safe and tolerable dose of gemcitabine in combination with once daily or twice daily dose of PTK/ZK in patients with unresectable pancreatic cancer. The Phase II part of this trial plans to determine the antitumor activity of this regimen and its effectiveness of preventing tumor growth and spread.


Condition Intervention Phase
Pancreatic Cancer
Drug: PTK787/ZK 222584
Drug: Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of the VEGF Receptor Tyrosine Kinase Inhibitor PTK787/ZK 222584 and Gemcitabine in Patients With Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Optimal safe and tolerable dose (MTD) of gemcitabine in combination with the 1250 mg continuous once daily dose of PTK/ZK. [ Time Frame: unknown ] [ Designated as safety issue: Yes ]
  • Efficacy, as reflected in objective response rate, of the PTK/ZK and gemcitabine combination in patients with advanced pancreatic cancer. [ Time Frame: unknown ] [ Designated as safety issue: No ]
  • Efficacy, as reflected in time to progression, of the PTK/ZK and gemcitabine combination in patients with advanced pancreatic cancer. [ Time Frame: unknown ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy, as reflected in overall survival, of the PTK/ZK and gemcitabine combination in patients with advanced pancreatic cancer. [ Time Frame: unknown ] [ Designated as safety issue: No ]
  • Effect of the PTK/ZK and gemcitabine combination on DCE-MRI determinants of tumor perfusion. [ Time Frame: unknown ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: October 2004
Study Completion Date: December 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: -1 Chemotherapy multiple agents systemic
Phase I: Gem 700 mg/m2 + PTK 1000 mg daily
Drug: PTK787/ZK 222584
250 mg PO Q12 x 7 days, 8th day forward 500 mg PO Q12
Other Name: Vatalanib
Drug: Gemcitabine
850 mg/m2
Other Name: Gemcitabine
Experimental: -2 Chemotherapy multiple agents systemic
Phase I: Gem 500 mg/m2 + PTK 1000 mg daily
Drug: PTK787/ZK 222584
250 mg PO Q12 x 7 days, 8th day forward 500 mg PO Q12
Other Name: Vatalanib
Drug: Gemcitabine
850 mg/m2
Other Name: Gemcitabine
Experimental: -3 Chemotherapy multiple agents systemic
Phase I: Gem 500 mg/m2 + PTK 750 mg daily
Drug: PTK787/ZK 222584
250 mg PO Q12 x 7 days, 8th day forward 500 mg PO Q12
Other Name: Vatalanib
Drug: Gemcitabine
850 mg/m2
Other Name: Gemcitabine
Experimental: 0 Chemotherapy multiple agents systemic
Phase I: Gem 700 mg/m2 + PTK 1250 mg daily
Drug: PTK787/ZK 222584
250 mg PO Q12 x 7 days, 8th day forward 500 mg PO Q12
Other Name: Vatalanib
Drug: Gemcitabine
850 mg/m2
Other Name: Gemcitabine
Experimental: 1 Chemotherapy multiple agents systemic
1 Phase I: Gem 850 mg/m2 + PTK 1250 mg
Drug: PTK787/ZK 222584
250 mg PO Q12 x 7 days, 8th day forward 500 mg PO Q12
Other Name: Vatalanib
Drug: Gemcitabine
850 mg/m2
Other Name: Gemcitabine
Experimental: 2 Chemotherapy multiple agents systemic
Phase I: Gem 850 mg/m2 + PTK 250 mg Q12 hours x 1 week then 500 mg Q12 hours thereafter
Drug: PTK787/ZK 222584
250 mg PO Q12 x 7 days, 8th day forward 500 mg PO Q12
Other Name: Vatalanib
Drug: Gemcitabine
850 mg/m2
Other Name: Gemcitabine
Experimental: 2-1 Registration
Phase II: dose TBD in Phase I
Drug: PTK787/ZK 222584
250 mg PO Q12 x 7 days, 8th day forward 500 mg PO Q12
Other Name: Vatalanib
Drug: Gemcitabine
850 mg/m2
Other Name: Gemcitabine

  Eligibility

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

Inclusion Criteria:- Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas. The site of the primary lesion should be confirmed endoscopically, radiologically, or surgically to be in the pancreas.

  • Patients must be deemed unresectable due to involvement of critical vasculature, adjacent organ invasion, or presence of metastasis.
  • Patients with a history of pancreatic adenocarcinoma treated by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic pancreatic adenocarcinoma if there is substantial clinical ambiguity regarding the nature or source of apparent metastases.
  • Patients must have a primary or metastatic lesion measurable in at least one dimension by Modified RECIST criteria (see Section 4.2) within 4 weeks prior to entry of study
  • Patients must have WHO performance status of 0-2
  • Patients must be >= 18 years of age
  • Laboratory values <= 2 weeks prior to randomization:
  • Absolute Neutrophil Count (ANC) >= 1.5 x 10^9/L (>= 1500/mm3)
  • Platelets (PLT) >= 100 x 10^9/L (>=100,000/mm3)
  • Hemoglobin (Hgb) >= 9 g/dL
  • Serum creatinine <= 1.5 ULN
  • Serum bilirubin <= 1.5 ULN
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <= 3.0 x ULN (<= 5 x ULN if liver metastases present). Note: ERCP or percutaneous stenting may be used to normalize the liver function tests.
  • Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein <= 500 mg and measured creatinine clearance (CrCl) >= 50 mL/min from a 24-hour urine collection
  • Life expectancy >= 12 weeks
  • Ability to give written informed consent according to local guidelines

Exclusion Criteria:- For the phase I portion of the study, patients receiving prior gemcitabine will be excluded from enrollment. For the phase II portion of the study, patients receiving any prior chemotherapy (except for low-dose 5-fluorouracil as a radiosensitizer) will be excluded from enrollment. Patients must have recovered from all therapy-related toxicities.

  • Prior full field radiotherapy <= 4 weeks or limited field radiotherapy <= 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.
  • Prior biologic or immunotherapy <= 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
  • Prior therapy with anti-VEGF agents
  • History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis)
  • Patients with a history of another primary malignancy <= 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin
  • Major surgery (e.g. laparotomy) <= 4 weeks prior to enrollment. Minor surgery <= 2 weeks prior to enrollment. Insertion of a vascular access device is not considered major or minor surgery. Patients must have recovered from all surgery-related toxicities.
  • Concurrent use of other investigational agents and patients who have received investigational drugs <= 4 weeks prior to enrollment.
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial in both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of study treatment. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
  • Pre-existing peripheral sensory neuropathy with functional impairment >= CTCAE grade 2 neuropathy.
  • Pleural effusion or ascites that causes respiratory compromise (>= CTCAE grade 2 dyspnea)
  • QTc > 450 ms (male) or > 470 ms (female)
  • Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
  • Unstable angina pectoris
  • Symptomatic congestive heart failure
  • Myocardial infarction <= 6 months prior to registration and/or randomization
  • Serious uncontrolled cardiac arrhythmia
  • Uncontrolled diabetes
  • Active or uncontrolled infection
  • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • Chronic renal disease
  • Acute or chronic liver disease (e.g., hepatitis, cirrhosis)
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK/ZK (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets)
  • Patients with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if he/she feels that 1) a potential drug interaction between PTK/ZK and any of the patient's anti-HIV medications could influence the efficacy of the anti-HIV medication, or 2) it may place the patient at risk due to the pharmacologic activity of PTK/ZK. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
  • Patients who are taking therapeutic warfarin sodium (Coumadin) or similar oral anticoagulants that are metabolized by the cytochrome P450 system. Heparin is allowed. Please refer to appendix for a list of examples of substrates of human liver microsomal P450 enzymes
  • Patients unwilling to or unable to comply with the protocol
  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: NCT00185588

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
George Albert Fisher
Novartis
Investigators
Principal Investigator: George Albert Fisher M.D. Ph.D. Stanford University
  More Information

No publications provided

Responsible Party: George Albert Fisher, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00185588     History of Changes
Other Study ID Numbers: PANC0002, 95533, CPTK787AUS08, 6999
Study First Received: September 12, 2005
Last Updated: November 6, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Vatalanib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014