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

NCT ID: NCT00413322

Last Updated: 2015-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2008-06-30

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).

Conditions

Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single-arm dose escalation

Group Type: EXPERIMENTAL

belinostat

Intervention Type: DRUG

300, 600, or 1000 mg/m2 belinostat IV for 5 days every 21 days starting with cycle 1

5-Fluorouracil (5-FU)

Intervention Type: DRUG

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.

Interventions

belinostat

300, 600, or 1000 mg/m2 belinostat IV for 5 days every 21 days starting with cycle 1

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

PXD101; 5-FU

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Valerio Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Topotarget A/S

Role: STUDY_CHAIR

Valerio Therapeutics

Locations

Mayo Clinic Arizona

Scottsdale, Arizona, United States

University of Nebraska

Omaha, Nebraska, United States

Portsmouth Regional Hospital Hematology/Oncology Clinic

Portsmouth, New Hampshire, United States

Countries

United States

Other Identifiers

PXD101-CLN-4

Identifier Type: -

Identifier Source: org_study_id