Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy Study of PTK787/ZK222584 to Treat Metastatic Neuroendocrine Tumors (PTK787)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00590343
Recruitment Status : Completed
First Posted : January 10, 2008
Last Update Posted : June 29, 2011
Sponsor:
Collaborator:
Novartis
Information provided by:
Louisiana State University Health Sciences Center in New Orleans

Tracking Information
First Submitted Date  ICMJE December 26, 2007
First Posted Date  ICMJE January 10, 2008
Last Update Posted Date June 29, 2011
Study Start Date  ICMJE November 2004
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 9, 2008)
Change in biochemical markers. [ Time Frame: Quarterly= every 3 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00590343 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2008)
Tumor response per triphasic CT scan. [ Time Frame: Quarterly= every 3 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of PTK787/ZK222584 to Treat Metastatic Neuroendocrine Tumors
Official Title  ICMJE An Open-label Phase II Study Evaluating the Safety and Efficacy of PTK787/ZK222584 in Patients With Metastatic Neuroendocrine Tumors That Have Evidence of Progressive Disease or an Increase in Disease Related Syndrome Symptoms.
Brief Summary The purpose of this study is to examine if PTK787/ZK222584 (vatalanib) will stabilize or decrease rising biochemical markers along with progressive disease or syndrome symptoms in patients with metastatic neuroendocrine tumors.
Detailed Description This is an open-label, phase II study evaluating the safety and efficacy of PTK787/ZK222584 administered daily in subjects with neuroendocrine tumors that are experiencing progressive disease and/or whose tumor-related syndrome symptoms (flushing and diarrhea) are considered inadequately controlled despite optimal doses of octreotide therapy. Inadequate control is defined as a minimum of 2 flushing episodes or 6 bowel movements per day for 7 consecutive days. Subjects who meet all inclusion and exclusion criteria and have completed all baseline and screening testing will receive an initial dose of PTK787/ZK222584 1,250 mg once daily and subjects will also remain on the scheduled doses of Sandostatin LAR 30 mg every 4 weeks. Both drugs will be dosed on a flat schedule of mg, not by weight or body surface area. The PTK787/ZK222584 medication will be taken orally with daily dosing. Each tablet of PTK787/ZK 222584 is 250 mg. The subject will take five tablets of study medication per day 2 tabs am and 3 tabs pm. Subjects may continue to receive therapy as long as they do not experience unacceptable toxicities or evidence of disease progression as defined by RECIST criteria. Subjects will be evaluated with a daily log to assess the degree of symptom control (flushing and diarrhea) and subjects will be monitored every 2 weeks for 3 months then monthly for biochemical control and every three months for tumor response. Subjects will be monitored by the Investigator every two weeks for 3 months then monthly for safety and efficacy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Neuroendocrine Tumors
Intervention  ICMJE Drug: vatalanib
Subjects who meet all inclusion and exclusion criteria will receive an initial dose of PTK787/ZK222584 1,250mg once daily, and subjects will remain on the scheduled doses of Sandostatin LAR 30mg every 4 weeks.
Study Arms  ICMJE Experimental: 1
Intervention=Patients will receive treatment with PTK787/ZK222584 daily. A treatment cycle will be defined as a 28-day period. Subjects will continue on their present treatment regimen of receiving Sandostatin LAR 30mg IM every 4 weeks.
Intervention: Drug: vatalanib
Publications * Drevs J, Müller-Driver R, Wittig C, Fuxius S, Esser N, Hugenschmidt H, Konerding MA, Allegrini PR, Wood J, Hennig J, Unger C, Marmé D. PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res. 2002 Jul 15;62(14):4015-22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 28, 2011)
23
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2008)
35
Actual Study Completion Date  ICMJE October 2010
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Biopsy-proven metastatic neuroendocrine tumors (which extent is disease is determined by CT scan or MRI) and biochemical evidence of disease.
  • Evidence of progressive disease or inadequate controlled disease related syndrome symptoms.
  • Must be receiving Sandostatin LAR 30mg every 4 weeks
  • Age >or= to 18 years old
  • Karnofsky Performance Status > or = 60
  • Measurable lesion(s) as per the modified RECIST criteria
  • Laboratory values <or= 2 weeks prior to randomization: ANC >or= 1.5 x 10(9)/L, Platelets >or= 100 x 10 (9), Hemoglobin >or= 9g/dL, Serum creatinine <or= 1.5 ULN, Serum bilirubin <or= 1.5 ULN, Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <or= 3.0 x ULN (<or= 5 x ULN if liver metastases present), Negative for proteinuria based on dip stick reading OR documentation of 1+ result for protein on dip stick reading, then total urinary protein <or= 500mg and measured creatinine clearance >or= 50ml/min from a 24 hour urine collection.
  • Life expectancy >or= 12 weeks.
  • Written informed consent obtained according to local guidelines.

Exclusion Criteria:

  • Had previous radiolabeled somatostatin analog therapy within the last 6 months.
  • Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease)
  • Undergone cryoablation of hepatic metastasis within the last 2 months.
  • History or presence of central nervous system (CNS) disease (ie:primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis)
  • History of another primary malignancy <or= 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin.
  • Prior chemotherapy <or= 3 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities.
  • Prior biologic or immunotherapy <or= 2 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities.
  • Prior full field radiotherapy <or= 4 weeks or limited field radiotherapy <or= 2 weeks prior to randomization. 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.
  • Major surgery (ie:laparotomy) <or= 4 weeks prior to randomization. Minor surgery <or= 2 weeks prior to randomization. Insertion of a vascular access device is not considered major or minor surgery in this regard. Patients must have recovered from all surgery-related toxicities.
  • Patients who have received investigational drugs <or= 4 weeks prior to registration.
  • Prior therapy with anti-VEGF agents
  • Pleural effusion or ascites that causes respiratory compromise (>or= CTC grade 2 dyspnea)
  • 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, 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.
  • 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 <or= 6 months prior to registration
  • Active or uncontrolled infection
  • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • Chronic renal disease
  • Subjects at risk of significant cardiac arrythmias
  • Uncontrolled diabetes
  • Acute or chronic liver disease (eg:hepatitis, cirrhosis)
  • Impairment of gastrointestinal function or GI disease that may significantly alter absorption (ie:ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets.)
  • Confirmed diagnosis of human immunodeficiency syndrome (HIV) infection are excluded at the investigator's discretion.
  • Patients taking therapeutic warfarin sodium (Coumadin) or similar oral anticoagulants that are metabolized by the cytochrome P450 system. Heparin is allowed.
  • Patients unwilling or unable to comply with the protocol.
  • Known symptomatic gallstones
  • Received glucocorticoid therapy within the past 6 months, or who are currently receiving any chemotherapeutic agents, insulin sensitizers (eg:metformin, pioglitazone, rosiglitazone), or exogenous growth hormones.
  • Subjects with unacceptable concomitant diagnoses, or who have received medication and/or therapies (ie:illness or therapies that would place patient at increased risk, or would, in the opinion of the investigator, interfere with the evaluation of efficacy or safety.)
  • Exhibit symptoms indicative of intolerance of Sandostatin LAR.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00590343
Other Study ID Numbers  ICMJE PTK787/ZK222584
LSU IRB-6355
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lowell Anthony, MD, Louisiana State University Health Sciences Center-New Orleans
Study Sponsor  ICMJE Louisiana State University Health Sciences Center in New Orleans
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: Lowell B Anthony, MD Lousiana State University Health Sciences Center-NO
PRS Account Louisiana State University Health Sciences Center in New Orleans
Verification Date June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP