Phase 1-2 Vatalanib 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: September 10, 2014
Last verified: September 2014
  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 study planned to determine the antitumor activity of this regimen and its effectiveness of preventing tumor growth and spread.


Condition Intervention Phase
Pancreatic Cancer
Drug: Vatalanib
Drug: Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1-2 Study of the VEGF Receptor Tyrosine Kinase Inhibitor PTK787/ZK 222584 <Vatalanib> and Gemcitabine in Patients With Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Time-to-Treatment Failure (Intent-To-Treat Analysis) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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).



Secondary Outcome Measures:
  • Time-to-Progression, Evaluable Patients [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.


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: 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:
  • Vatalanib
  • PTK787
  • ZK 222584
  • PTK787/ZK 222584
Drug: Gemcitabine
850 mg/m2
Other Names:
  • Gemcitabine
  • 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:
  • Vatalanib
  • PTK787
  • ZK 222584
  • PTK787/ZK 222584
Drug: Gemcitabine
850 mg/m2
Other Names:
  • Gemcitabine
  • 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:
  • Vatalanib
  • PTK787
  • ZK 222584
  • PTK787/ZK 222584
Drug: Gemcitabine
850 mg/m2
Other Names:
  • Gemcitabine
  • 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:
  • Vatalanib
  • PTK787
  • ZK 222584
  • PTK787/ZK 222584
Drug: Gemcitabine
850 mg/m2
Other Names:
  • Gemcitabine
  • Gemzar

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: IRB-06999, 95533, CPTK787AUS08, PANC0002
Study First Received: September 12, 2005
Results First Received: July 30, 2014
Last Updated: September 10, 2014
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 September 30, 2014