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

• ClinicalTrials.gov Identifier: NCT00413322
• Recruitment Status: Completed
• First Posted: December 19, 2006
• Last Update Posted: July 8, 2015
• Sponsor: Onxeo
• Information provided by (Responsible Party): Onxeo

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Tumor	Drug: belinostat; Drug: 5-Fluorouracil (5-FU)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2005
• Actual Primary Completion Date: March 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single-arm dose escalation	Drug: belinostat; 300, 600, or 1000 mg/m2 belinostat IV for 5 days every 21 days starting with cycle 1; Other Name: PXD101; Drug: 5-Fluorouracil (5-FU); 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.; Other Name: 5-FU

Outcome Measures

Primary Outcome Measures :

1. to determine the maximum tolerated dose of PXD101 administered in combination with 5-FU [ Time Frame: throughout the study ]
2. to determine whether PXD101 alone can down-regulate thymidylate synthase in patient tumors [ Time Frame: throughout the study ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Arizona

Scottsdale, Arizona, United States, 85259

United States, Nebraska

University of Nebraska

Omaha, Nebraska, United States, 68198-7680

United States, New Hampshire

Portsmouth Regional Hospital Hematology/Oncology Clinic

Portsmouth, New Hampshire, United States, 03801

Sponsors and Collaborators

Onxeo

Investigators

• Study Chair: Topotarget A/S; Onxeo

More Information

• Responsible Party: Onxeo
• ClinicalTrials.gov Identifier: NCT00413322
• Other Study ID Numbers: PXD101-CLN-4
• First Posted: December 19, 2006
• Last Update Posted: July 8, 2015
• Last Verified: July 2015

Keywords provided by Onxeo:

mesothelioma; mesothelioma, cystic; 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; Mixed Tumor, Mesodermal; Mouth Neoplasms

Additional relevant MeSH terms:

Neoplasms; Fluorouracil; Belinostat; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Histone Deacetylase Inhibitors; Enzyme Inhibitors