FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00769288
• Other study ID #: NCI-2009-00248
• Secondary ID: NCI-2009-00248CD
• Status: Completed
• Phase: Phase 1
• First received: October 8, 2008
• Last updated: January 6, 2014
• Start date: July 2009

Study information

• Verified date: January 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Grade III Lymphomatoid Granulomatosis
• Adult Nasal Type Extranodal NK/T-cell Lymphoma
• Anaplastic Large Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Burkitt Lymphoma
• Cutaneous B-cell Non-Hodgkin Lymphoma
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Hodgkin Disease
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Extranodal NK-T-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphomatoid Granulomatosis
• Mycoses
• Mycosis Fungoides
• Nodal Marginal Zone B-cell Lymphoma
• Recurrent Adult Burkitt Lymphoma
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Adult Diffuse Mixed Cell Lymphoma
• Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
• Recurrent Adult Grade III Lymphomatoid Granulomatosis
• Recurrent Adult Hodgkin Lymphoma
• Recurrent Adult Immunoblastic Large Cell Lymphoma
• Recurrent Adult Lymphoblastic Lymphoma
• Recurrent Adult T-cell Leukemia/Lymphoma
• Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
• Recurrent Grade 1 Follicular Lymphoma
• Recurrent Grade 2 Follicular Lymphoma
• Recurrent Grade 3 Follicular Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Marginal Zone Lymphoma
• Recurrent Mycosis Fungoides/Sezary Syndrome
• Recurrent Small Lymphocytic Lymphoma
• Sezary Syndrome
• Small Intestine Lymphoma
• Splenic Marginal Zone 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 Adult T-cell Leukemia/Lymphoma
• Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
• 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 Mycosis Fungoides/Sezary Syndrome
• 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
• Stage IV Adult Hodgkin Lymphoma
• Stage IV Adult Immunoblastic Large Cell Lymphoma
• Stage IV Adult Lymphoblastic Lymphoma
• Stage IV Adult T-cell Leukemia/Lymphoma
• Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
• Stage IV Grade 1 Follicular Lymphoma
• Stage IV Grade 2 Follicular Lymphoma
• Stage IV Grade 3 Follicular Lymphoma
• Stage IV Mantle Cell Lymphoma
• Stage IV Marginal Zone Lymphoma
• Stage IV Mycosis Fungoides/Sezary Syndrome
• Stage IV Small Lymphocytic Lymphoma
• Syndrome
• Unspecified Adult Solid Tumor, Protocol Specific
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• 2'-F-ara-deoxyuridine
Given IV

Other:
• positron emission tomography
Correlative studies
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies
• pharmacogenomic studies
Correlative studies

Locations

Country	Name	City	State
United States	Wayne State University	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Up to 28 days	Yes
Secondary	Clinical response to FAU, evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee	Response will be described by point estimates and exact confidence intervals.	Up to 30 days	No
Secondary	Pharmacokinetics of FAU, including Cmax, Tmax, AUC 0-last, AUC 0-infinity, CL, t1/2, and Vss	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	No