Phase 1-2 Vatalanib and Gemcitabine in Advanced Pancreatic Cancer

• Status: Completed
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: George Albert Fisher
• Collaborator: Novartis
• Treatments: Gemcitabine; Vatalanib

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