FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

January 6, 2014 updated by: National Cancer Institute (NCI)

A Phase I Study of Intravenously Administered FAU (1-(2'-Deoxy-2'-Fluoro-B-D-arabinofuranosyl) Uracil, NSC#678515) in Patients With Advanced Solid Tumors

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

Study Overview

Status

Completed

Conditions

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of FAU in patients with advanced solid tumors or lymphoma.

II. To determine the dose-limiting toxicity and maximum tolerated dose (MTD) of FAU in these patients.

SECONDARY OBJECTIVES:

I. To observe the clinical response in patients treated with FAU. II. To characterize the pharmacokinetics of FAU in these patients. III. 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.

IV. 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.

V. 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.

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

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Michigan
      • Detroit, Michigan, United States, 48202
        • Wayne State University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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 but previously treated brain metastases allowed
  • ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
  • 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
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin C, or bleomycin), immunotherapy, or experimental therapy and recovered
  • More than 4 weeks since prior radiotherapy to > 5% of total marrow volume
  • No prior radiotherapy to >= 50% of total marrow volume
  • More than 3 weeks since prior radiotherapy to =< 5% of total marrow volume
  • No other concurrent investigational agents
  • ANC >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Life expectancy > 12 weeks
  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: I
Patients will receive a 1-hour infusion of FAU on days 1-5.
Correlative studies
Correlative studies
Other Names:
  • pharmacological studies
Correlative studies
Other Names:
  • Pharmacogenomic Study
Given IV
Other Names:
  • FAU
Correlative studies
Other Names:
  • PET
  • FDG-PET
  • PET scan
  • tomography, emission computed

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose, defined as the dose at which no more than 1/6 patients develops dose-limiting toxicity, graded by NCI CTCAE version 4.0
Time Frame: Up to 28 days
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical response to FAU, evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
Time Frame: Up to 30 days
Response will be described by point estimates and exact confidence intervals.
Up to 30 days
Pharmacokinetics of FAU, including Cmax, Tmax, AUC 0-last, AUC 0-infinity, CL, t1/2, and Vss
Time Frame: Days 1 and 22 of course 1 at pre-treatment; at the end of infusion; and following the end of infusion at 15 and 30 minutes and 1, 2, 4, 8, and 24 hours
All pharmacokinetic parameters will be summarized with standard descriptive statistics.
Days 1 and 22 of course 1 at pre-treatment; at the end of infusion; and following the end of infusion at 15 and 30 minutes and 1, 2, 4, 8, and 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

October 8, 2008

First Submitted That Met QC Criteria

October 8, 2008

First Posted (Estimate)

October 9, 2008

Study Record Updates

Last Update Posted (Estimate)

January 7, 2014

Last Update Submitted That Met QC Criteria

January 6, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00248 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA022453 (U.S. NIH Grant/Contract)
  • U01CA062487 (U.S. NIH Grant/Contract)
  • CDR0000615651
  • WSU#2007-005
  • WSU-2007-005 (Other Identifier: Wayne State University)
  • 7916 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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