Phase 1-2 Vatalanib and Gemcitabine in Advanced Pancreatic Cancer

NCT ID: NCT00185588

Last Updated: 2014-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2009-12-31

Brief Summary

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 study planned to determine the antitumor activity of this regimen and its effectiveness of preventing tumor growth and spread.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stage 1 Dose Exploration 0 - Gemcitabine 700 + vatalanib 1250

Gemcitabine 700 mg/m2 + vatalanib 1250 mg daily

Group Type: EXPERIMENTAL

Vatalanib

Intervention Type: DRUG

Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours

Gemcitabine

Intervention Type: DRUG

850 mg/m2

Stage 1 Dose Exploration 1 - Gemcitabine 850 + vatalanib 1250

Gemcitabine 850 mg/m2 + vatalanib 1250 mg

Group Type: EXPERIMENTAL

Vatalanib

Intervention Type: DRUG

Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours

Gemcitabine

Intervention Type: DRUG

850 mg/m2

Stage 1 Dose Explrtion2 - Gemcitabine850+vatalanib 2x250/2x500

Gemcitabine 850 mg/m2 + vatalanib 250 mg Q12 hours x 1 week then 500 mg Q12 hours thereafter

Group Type: EXPERIMENTAL

Vatalanib

Intervention Type: DRUG

Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours

Gemcitabine

Intervention Type: DRUG

850 mg/m2

Stage 2 Dose Expansion - Gemcitabine850+vatalanib 2x250/2x500

Gemcitabine 850 mg/m2 + vatalanib 250 mg Q12 hours x 1 week then 500 mg Q12 hours thereafter

Group Type: EXPERIMENTAL

Vatalanib

Intervention Type: DRUG

Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours

Gemcitabine

Intervention Type: DRUG

850 mg/m2

Interventions

Vatalanib

Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours

Intervention Type: DRUG

Gemcitabine

850 mg/m2

Intervention Type: DRUG

Other Intervention Names

PTK787; ZK 222584; PTK787/ZK 222584; Gemzar

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Unresectable (due to involvement of critical vasculature, adjacent organ invasion, or presence of metastasis)
• If > 5 years between the primary surgery and the development of metastatic disease, then separate histological or cytological confirmation of metastatic disease
• Primary or metastatic lesion within 4 weeks prior to entry of study
• WHO performance status of 0 to 2
• ≤ 18 years of age
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 10e9/L (>= 1500/mm3)
• Platelets (PLT) ≥ 100 x 10^9/L (≥ 100,000/mm3)
• Hemoglobin (Hgb) ≥ 9 g/dL
• Serum creatinine ≤ 1.5 upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 ULN
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase

• (ALT/SGPT) ≤ 3.0 x ULN OR
• ≤ 5 x ULN if liver metastases present
• Proteinuria:

• Negative for proteinuria based on dip stick reading OR
• If dip stick reading is +1 result, 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

Exclusion Criteria

• For the "phase 1" portion of the study: prior gemcitabine will be therapy.
• For the "phase 2" portion of the study: any prior chemotherapy {except for low-dose 5-fluorouracil (5-FU)as a radiosensitizer]
• Radiotherapy (RT). The site of previous RT must have progressive disease if the only site of disease).

• Prior full field radiotherapy ≤ 4 weeks prior to enrollment OR
• Limited field radiotherapy ≤ 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities.
• Prior biologic or immunotherapy ≤ 2 weeks prior to registration.
• Prior therapy with anti-VEGF agents
• History or presence of central nervous system (CNS) disease
• Patients with a history of another primary malignancy ≤ 5 years (Exception: inactive basal or squamous cell carcinoma of the skin)
• Major surgery ≤ 4 weeks prior to enrollment. (Exception: insertion of a vascular access device)
• Minor surgery ≤ 2 weeks prior to enrollment. (Exception: insertion of a vascular access device)
• Concurrent use of other investigational agents and patients who have received investigational drugs ≤ 4 weeks prior to enrollment.
• Pregnant, or breast-feeding, not employing an effective method of birth control.
• Pre-existing peripheral sensory neuropathy with functional impairment (≥ CTCAE grade 2 neuropathy)
• Respiratory compromise due to pleural effusion or ascites (≥ CTCAE grade 2 dyspnea)
• QTc > 450 ms (male) or > 470 ms (female)
• Uncontrolled high blood pressure
• History of labile hypertension
• History of poor compliance with an antihypertensive regimen
• Unstable angina pectoris
• Symptomatic congestive heart failure
• Myocardial infarction ≤ 6 months prior to registration / randomization
• Serious uncontrolled cardiac arrhythmia
• Uncontrolled diabetes
• Active or uncontrolled infection
• Interstitial pneumonia
• Extensive and symptomatic interstitial fibrosis of the lung
• Chronic renal disease
• Acute or chronic liver disease
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of vatalanib
• Human immunodeficiency virus (HIV) infection (confirmed), if there is potential for interaction between vatalanib and any anti-HIV medication
• HIV infection (confirmed) judged to increase subject risk due to the pharmacologic activity of vatalanib
• Receiving warfarin sodium (Coumadin) or similar. Heparin is allowed.
• Unwilling to or unable to comply with

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

George Albert Fisher

OTHER

Sponsor Role: lead

Responsible Party

George Albert Fisher

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

George Albert Fisher M.D. Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

95533

Identifier Type: OTHER

Identifier Source: secondary_id

CPTK787AUS08

Identifier Type: OTHER

Identifier Source: secondary_id

PANC0002

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-06999

Identifier Type: -

Identifier Source: org_study_id