Phase 1-2 Vatalanib and Gemcitabine in Advanced Pancreatic Cancer

A Phase 1-2 Study of the VEGF Receptor Tyrosine Kinase Inhibitor PTK787/ZK 222584 <Vatalanib> and Gemcitabine in Patients With Advanced Pancreatic Cancer

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Vatalanib; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1 Dose Exploration 0 - Gemcitabine 700 + vatalanib 1250; Gemcitabine 700 mg/m2 + vatalanib 1250 mg daily	Drug: Vatalanib; Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours; Other Names: PTK787/ZK 222584; PTK787; ZK 222584; Drug: Gemcitabine; 850 mg/m2; Other Names: Gemzar
Experimental: Stage 1 Dose Exploration 1 - Gemcitabine 850 + vatalanib 1250; Gemcitabine 850 mg/m2 + vatalanib 1250 mg	Drug: Vatalanib; Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours; Other Names: PTK787/ZK 222584; PTK787; ZK 222584; Drug: Gemcitabine; 850 mg/m2; Other Names: Gemzar
Experimental: 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	Drug: Vatalanib; Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours; Other Names: PTK787/ZK 222584; PTK787; ZK 222584; Drug: Gemcitabine; 850 mg/m2; Other Names: Gemzar
Experimental: 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	Drug: Vatalanib; Vatalanib 250 mg PO Q12 hours x 7 days, 8th day forward 500 mg PO Q12 hours; Other Names: PTK787/ZK 222584; PTK787; ZK 222584; Drug: Gemcitabine; 850 mg/m2; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Treatment Failure (Intent-To-Treat Analysis)	For the purposes of an Intent-to-Treat (ITT) analysis, Time-to-Treatment Failure (TTF) was defined as the time from treatment initiation to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, lost-to-follow-up, or death. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Progression, Evaluable Patients	Represents the evaluable subset of subjects that terminated from the study due to disease progression (endpoint). Does not include any other form of treatment failure, nor lost-to-follow-up.	12 months

Collaborators and Investigators

• Sponsor: George Albert Fisher
• Collaborators: Novartis

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 16, 2005

Study Record Updates

• Last Update Posted (Estimate): September 15, 2014
• Last Update Submitted That Met QC Criteria: September 10, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Vatalanib
• Other Study ID Numbers: IRB-06999; 95533 (Other Identifier: Stanford University Alternate IRB Number); CPTK787AUS08 (Other Identifier: Novartis); PANC0002 (Other Identifier: OnCore)