FAU in Treating Patients With Advanced Solid Tumors or Lymphoma - Full Text View

Sponsors and Collaborators:	Barbara Ann Karmanos Cancer Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00769288

Purpose

RATIONALE: Drugs used in chemotherapy, such as FAU, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of FAU in treating patients with advanced solid tumors or lymphoma.

Condition	Intervention	Phase
Lymphoma Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: FAU Procedure: gene expression analysis Procedure: high performance liquid chromatography Procedure: immunohistochemistry staining method Procedure: laboratory biomarker analysis Procedure: mass spectrometry Procedure: pharmacogenomic studies Procedure: pharmacological study Procedure: polymerase chain reaction Procedure: polymorphism analysis Procedure: positron emission tomography Procedure: protein expression analysis Procedure: western blotting	Phase I

MedlinePlus related topics: Cancer Fungal Infections Hodgkin's Disease Intestinal Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Uracil

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of Intravenously Administered FAU (1-(2'-Deoxy-2'-Fluoro-β-D-Arabinofuranosyl) Uracil, NSC# 678515) in Patients With Advanced Solid Tumors

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Dose-limiting toxicity of FAU as assessed by NCI CTCAE version 3.0 [ Designated as safety issue: Yes ]
Maximum tolerated dose of FAU [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response [ Designated as safety issue: No ]
Pharmacokinetics of FAU [ Designated as safety issue: No ]
Relationship between pre- and post-treatment 18F-FAU PET standardized uptake value levels and time to tumor progression [ Designated as safety issue: No ]
Comparison of protein levels of thymidylate synthase (TS) in archival tumor tissue samples with thymidine kinase (TK) and TS protein levels and TK and TS mRNA levels in fresh tumor tissue samples [ Designated as safety issue: No ]
Relationship between genetic polymorphisms of TS and tumor 18F-FAU uptake [ Designated as safety issue: No ]

Estimated Enrollment:	49
Study Start Date:	May 2007
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To assess the safety and tolerability of FAU in patients with advanced solid tumors or lymphoma.
To determine the dose-limiting toxicity and maximum tolerated dose (MTD) of FAU in these patients.

Secondary

To observe the clinical response in patients treated with FAU.
To characterize the pharmacokinetics of FAU in these patients.
To explore whether an association exists between pre-treatment ^18F-FAU PET standardized uptake value levels and time to tumor progression after treatment with unlabeled FAU.
To estimate the protein levels of thymidylate synthase (TS) in archival tumor tissue samples and to compare them with thymidine kinase (TK) and TS protein levels and TK and TS mRNA levels in fresh tumor tissue samples from patients treated at the MTD.
To explore the relationship between genetic polymorphisms of TS and tumor ^18F-FAU uptake.

OUTLINE: This is a multicenter study.

Patients receive FAU IV over 1 hour on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood and urine samples are collected periodically for pharmacokinetic studies using high performance liquid chromatography with tandem mass spectrometry. Archival tumor tissue samples are obtained for pharmacodynamic and pharmacogenomic studies, including analysis of thymidylate synthase (TS) polymorphisms by PCR and polyacrylamide gel electrophoresis and analysis of TS expression by IHC. Patients treated with FAU at the maximum tolerated dose also undergo tumor tissue biopsies for additional pharmacodynamic studies, including analysis of thymidine kinase (TK) and TS expression (protein and mRNA expression) by western blotting and PCR and analysis of TK and TS enzyme activity by assay.

Patients undergo PET imaging with ^18F-FAU at baseline and on day 1 of course 1 (after the first infusion of unlabeled FAU) for correlative imaging studies.

After completion of study therapy, patients are followed for 30 days.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed malignant solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- Solid hematologic malignancies (e.g., Hodgkin or non-Hodgkin lymphoma) allowed provided bone marrow biopsy has been performed within the past 6 weeks
Metastatic or unresectable disease
Measurable disease by CT scan and/or MRI
Archival tumor tissue sample available for correlative pharmacodynamic and pharmacogenomic studies
Accessible tumor tissue available (for patients enrolled in the expanded maximum tolerated dose [MTD] cohort)
No known active brain metastases
- Previously treated brain metastases allowed

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 12 weeks
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if liver metastases are present)
Alkaline phosphatase ≤ 2.0 times ULN (≤ 5 times ULN if bone or liver metastases are present)
Bilirubin normal
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Willing to undergo tumor biopsies for correlative pharmacodynamic studies (for patients enrolled in the expanded MTD cohort)
Able to lie still for PET scan
Weight ≤ 300 lbs.
No uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situation that would preclude compliance with study requirements
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to FAU

PRIOR CONCURRENT THERAPY:

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin C, or bleomycin), immunotherapy, or experimental therapy and recovered
More than 3 weeks since prior radiotherapy to ≤ 5% of total marrow volume
More than 4 weeks since prior radiotherapy to > 5% of total marrow volume
No prior radiotherapy to ≥ 50% of total marrow volume
No other concurrent anticancer therapy (e.g., cytotoxic therapy, biologic therapy, radiotherapy, or hormonal therapy)
- Concurrent hormone replacement therapy allowed
- Concurrent megestrol acetate or bisphosphonates allowed provided they were started 1 month prior to study enrollment
- Concurrent luteinizing hormone-releasing hormone agonists to maintain castrate levels of testosterone allowed for patients with prostate cancer
No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00769288

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Patricia M. LoRusso, DO

Barbara Ann Karmanos Cancer Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000615651, WSU-2007-005
Study First Received:	October 8, 2008
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00769288
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific
recurrent adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma

stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage III mycosis fungoides/Sezary syndrome
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma

Study placed in the following topic categories:

Sezary syndrome
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Ileal Diseases
Lymphoma, large-cell, immunoblastic
Duodenal Neoplasms
Lymphomatoid granulomatosis
Mycoses
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Anaplastic
Hodgkin Disease
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders

Digestive System Neoplasms
Leukemia, B-cell, chronic
Waldenstrom Macroglobulinemia
B-cell lymphomas
Leukemia, T-Cell
Gastrointestinal Neoplasms
Anaplastic large cell lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Hodgkin's disease
Gastrointestinal Diseases
Cutaneous T-cell lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Sezary Syndrome

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Immune System Diseases
Jejunal Diseases

ClinicalTrials.gov processed this record on January 15, 2009