Brief Title
FAU in Treating Patients With Advanced Solid Tumors or Lymphoma
Official Title
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
Brief Summary
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.
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
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
Secondary Outcome
Clinical response to FAU, evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
Condition
Adult Grade III Lymphomatoid Granulomatosis
Intervention
2'-F-ara-deoxyuridine
Study Arms / Comparison Groups
I
Description: Patients will receive a 1-hour infusion of FAU on days 1-5.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
12
Start Date
July 2009
Primary Completion Date
December 2013
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Patricia LoRusso, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00769288
Organization ID
NCI-2009-00248
Secondary IDs
NCI-2009-00248
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Patricia LoRusso, Principal Investigator, Wayne State University
Verification Date
January 2014