Clinical trial NCT00413322: Study of PXD101 Alone and in Combination With 5-Fluorouracil (5-FU) in Patients With Advanced Solid Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tumor
Keywords: 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
Lead sponsor: Valerio Therapeutics
Sponsor class: INDUSTRY
First posted: 2006-12-19
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: to determine the maximum tolerated dose of PXD101 administered in combination with 5-FU
timeFrame: throughout the study
measure: to determine whether PXD101 alone can down-regulate thymidylate synthase in patient tumors
timeFrame: throughout the study
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Portsmouth
country: United States
facility: Portsmouth Regional Hospital Hematology/Oncology Clinic
state: New Hampshire
Study officials:
affiliation: Valerio Therapeutics
name: Topotarget A/S
role: STUDY_CHAIR
References: