Study of PXD101 Alone and in Combination With 5-Fluorouracil (5-FU) in Patients With Advanced Solid Tumors
This study has been completed.
Sponsor:
TopoTarget A/S
Information provided by (Responsible Party):
TopoTarget A/S
ClinicalTrials.gov Identifier:
NCT00413322
First received: December 18, 2006
Last updated: November 8, 2012
Last verified: December 2009
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Tumor |
Drug: belinostat Drug: 5-Fluorouracil (5-FU) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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 |
Resource links provided by NLM:
Further study details as provided by TopoTarget A/S:
Primary Outcome Measures:
- to determine the maximum tolerated dose of PXD101 administered in combination with 5-FU [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]
- to determine whether PXD101 alone can down-regulate thymidylate synthase in patient tumors [ Time Frame: throughout the study ] [ Designated as safety issue: No ]
| Enrollment: | 35 |
| Study Start Date: | September 2005 |
| Study Completion Date: | June 2008 |
| Primary Completion Date: | March 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413322
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
TopoTarget A/S
More Information
No publications provided
| Responsible Party: | TopoTarget A/S |
| ClinicalTrials.gov Identifier: | NCT00413322 History of Changes |
| Other Study ID Numbers: | PXD101-CLN-4 |
| Study First Received: | December 18, 2006 |
| Last Updated: | November 8, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by TopoTarget A/S:
|
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 |
Additional relevant MeSH terms:
|
Fluorouracil Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic |
Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 22, 2013