Study of PXD101 Alone and in Combination With 5-Fluorouracil (5-FU) in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a study to assess the combination of PXD101 and 5-Fluorouracil (5-FU)in patients with advanced solid tumors. The primary goal of the study is to understand the safety, anti-tumor activity, and how the study drug behaves within the body when given with 5-Fluorouracil (5-FU).

Official Title
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A Phase I Safety, Pharmacodynamic, Anti-Tumor Activity, and Pharmacokinetic Study of PXD101 Alone and in Combination With 5-Fluorouracil in Patients With Advanced Solid Tumors

Conditions
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Tumor

Intervention / Treatment
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* Drug: belinostat
* Drug: 5-Fluorouracil (5-FU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed solid tumors Advanced colorectal cancer or other adenocarcinomas Tumor progression after standard chemotherapy, or where none yet approved At least one unidimensionally measurable lesion Karnofsky performance >= 70% Life expectancy of at least 3 months Age >= 18 years Signed, written Institutional Review Board (IRB)-approved informed consent Acceptable liver function: Bilirubin <= 1.5 x upper limit of normal (ULN) AST (SGOT) and ALT (SGPT) <= 2.5 x ULN, OR AST (SGOT) and ALT (SGPT) <= 5 x ULN if liver metastasis Acceptable renal function: Serum creatinine within normal limits, OR Calculated creatinine clearance of >= 60 mL/min/1.73 m2 for certain patients Acceptable hematologic status: Absolute neutrophil count (ANC) >= 1500 cells/mm3 Platelet count >= 100,000 (plt/mm3) Hemoglobin >= 9 g/dL Urinalysis: No clinically significant abnormalities Acceptable coagulation status: Prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits, OR For patients on anticoagulation therapy, status within therapeutic range For men and women of child-producing potential, use of effective contraception Tumors accessible for needle biopsy Exclusion Criteria: Significant cardiovascular disease. A marked baseline prolongation of QT/QTc interval Long QT syndrome Required use of medication on dosing days that may cause torsade de pointes. Infections requiring intravenous (IV) systemic therapy Pregnant or nursing women Treatment with chemotherapy or investigational therapy < 4 weeks (28 days) prior to study entry (6 weeks for nitrosoureas, mitomycin C, or Avastin). Treatment with radiation therapy or surgery either within 2 weeks prior to study entry, or not yet recovered if 2-4 weeks prior to study entry. Unwillingness or inability to comply with protocol procedures. Known active uncontrolled infection with HIV, hepatitis B, or hepatitis C Serious nonmalignant disease (e.g. hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor Concurrent use of other investigational agent(s) Serious concurrent medical illness

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-arm dose escalation<br> | Drug: belinostat<br>* 300, 600, or 1000 mg/m2 belinostat IV for 5 days every 21 days starting with cycle 1<br>* Other names: PXD101;Drug: 5-Fluorouracil (5-FU)<br>* 250, 500, 750, or 1000 mg/m2/d of 5-FU starting with cycle 2 onwards in combination with belinostat. Starting on day 2, 5-FU is administered as a continuous 96 hour infusion.<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to determine the maximum tolerated dose of PXD101 administered in combination with 5-FU |  | throughout the study | 
| to determine whether PXD101 alone can down-regulate thymidylate synthase in patient tumors |  | throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid tumor, Adenosarcoma, Androgen-independent prostate cancer, belinostat, bladder cancer, bladder neoplasms, Breast cancer, Carcinoma, Bronchogenic, Carcinoma, Non-Small-Cell Lung, Carcinoma, Small Cell, Carcinosarcoma, Chondrosarcoma, Coin Lesion, Pulmonary, colorectal cancer, Esophageal Neoplasms, Facial Neoplasms, Fibrosarcoma, head and neck cancer, Hemangiosarcoma, Histiocytoma, Malignant Fibrous, kidney cancer, Leiomyosarcoma, Liposarcoma, lung cancer, lung neoplasms, Lymphangiosarcoma, mesothelioma, mesothelioma, cystic, Mixed Tumor, Mesodermal, Mouth Neoplasms, Myosarcoma, Myxosarcoma, Osteosarcoma, Otorhinolaryngologic Neoplasms, Ovarian cancer, Pancoast's Syndrome, Parathyroid Neoplasms, Phyllodes Tumor, Pulmonary Sclerosing Hemangioma, sarcoma, thyroid cancer, Thyroid Neoplasms, Tracheal Neoplasms, PXD101