Clinical trial NCT00769288: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-10-09
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
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
timeFrame: Up to 28 days
Secondary outcomes:
measure: Clinical response to FAU, evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
timeFrame: Up to 30 days
measure: Pharmacokinetics of FAU, including Cmax, Tmax, AUC 0-last, AUC 0-infinity, CL, t1/2, and Vss
timeFrame: 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
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
Study officials:
affiliation: Wayne State University
name: Patricia LoRusso
role: PRINCIPAL_INVESTIGATOR
References: