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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Adult Grade III Lymphomatoid Granulomatosis, Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, 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, 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, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

Up to 28 days

Safety Issue:

Yes

Principal Investigator

Patricia LoRusso

Investigator Role:

Principal Investigator

Investigator Affiliation:

Wayne State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00248

NCT ID:

NCT00769288

Start Date:

July 2009

Completion Date:

Related Keywords:

  • Adult Grade III Lymphomatoid Granulomatosis
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • 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
  • 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
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Neoplasms
  • Lymphoma, Mantle-Cell

Name

Location

Wayne State UniversityDetroit, Michigan  48202