The Safety and Efficacy of CPTK787/ZK222584 in Patients With Metastatic Neuroendocrine Tumors

Neuroendocrine Tumors Clinical Trial

— CPTK787  

Official title:

An Open Label Phase II Study Evaluating the Safety and Efficacy of CPTK787/ZK222584 in Patients With Metastatic Neuroendocrine Tumors That Have Evidence of Progressive Disease or an Increase in Disease Related Syndrome Symptoms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00627198
• Other study ID #: CPTK787/ZK222584
• Status: Completed
• Phase: Phase 2
• First received: February 20, 2008
• Last updated: December 1, 2010
• Start date: December 2006
• Est. completion date: November 2010

Study information

• Verified date: December 2010
• Source: University of Iowa
• 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, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion:

• Biopsy-proven metastatic neuroendocrine tumors and biochemical evidence of disease

• Evidence of progressive disease with measurable lesion(s) or inadequate controlled disease syndrome.

• Receiving Sandostatin LAR 30 mg q 4 weeks

• Age equal to or greater than 18 years

• Karnofsky Performance Status equal to or greater than 60

• Lab values within 2 weeks prior to randomization:

• Absolute Neutrophil Count equal to or greater than 1.5 x 109/L

• Platelets equal to or greater than 100 x 109/L

• Hemoglobin equal to or greater than 9 g/dL

• Serum creatinine & bilirubin equal to or less than 1.5 ULN

• AST & ALT equal to or less than 3.0 x ULN equal to or less than 5 x ULN if liver metastases present

• Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein equal to or less than 500 mg and measured creatinine clearance equal to or greater than 50 mL/min from a 24-hour urine collection

• Life expectancy 12 weeks or more

• Written informed consent obtained according to local guidelines

Exclusion:

• Previous radiolabeled somatostatin analog therapy within 6 months

• Hepatic artery embolization within 6 months (1 month if there are other sites of measurable disease)

• Cryoablation of hepatic metastasis within 2 months

• History or presence of CNS disease

• History of another primary malignancy equal to or less than 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin

• Prior chemotherapy within 3 weeks prior to randomization.

• Prior biologic or immunotherapy within 2 weeks prior to randomization.

• Prior full field radiotherapy or major surgery within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization.

• Must have recovered from all therapy-related toxicities.

• Minor surgery within 2 weeks prior to randomization.

• Any investigational drugs within 4 weeks prior to randomization

• Prior therapy with anti-VEGF agents

• Pleural effusion or ascites that causes respiratory compromise equal to or greater than 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. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to study treatment.

• 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 within 6 months prior to randomization

• Active or uncontrolled infection

• Interstitial pneumonia or extensive & symptomatic interstitial fibrosis of the lung

• Chronic renal disease

• Subjects at risk of significant cardiac arrhythmias

• Uncontrolled diabetes

• Acute or chronic liver disease

• Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of PTK787/ZK 222584

• A confirmed diagnosis of human immunodeficiency virus infection are excluded at the investigator's discretion

• If you are taking therapeutic warfarin sodium or similar oral anticoagulants. Heparin is allowed.

• If you are unwilling to or unable to comply with the protocol

• If you have symptomatic gallstones

• If you have received glucocorticoid therapy within 6 months, or who are currently receiving any chemotherapeutic agents, insulin sensitizers, or exogenous growth hormones

• If you have unacceptable concomitant diagnoses, or who have received medication and/or therapies that would place the patient at increase risk, or would in the opinion of the investigator, interfere with the evaluation of efficacy and safety

• If you exhibit symptoms indicative of intolerance of Sandostatin LAR

Study Design

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

Related Conditions & MeSH terms

• Carcinoid Tumor
• Neuroendocrine Tumors

Intervention

Drug:
• PTK787/ZK222584 - Experimental
250mg tablets; 500mg (2 tablets) in the am and 750mg (3 tablets) in the pm.

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
University of Iowa	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the efficacy of PTK787/ZK 222584 in subjects with metastatic neuroendocrine tumors that have evidence of progressive disease or an increase in disease related syndrome symptoms as evidence by changes in biochemical markers.		Until disease progression	Yes
Secondary	To assess the safety and tolerability of PTK787/ZK222584 in subjects with metastatic neuroendocrine disease who are receiving octreotide therapy.		Until disease progression	Yes