FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

Phase 1

Completed

• Conditions: Adult Nasal Type Extranodal NK/T-cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Anaplastic Large Cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma
• Interventions: Drug: 2'-F-ara-deoxyuridine; Other: positron emission tomography; Other: laboratory biomarker analysis; Other: pharmacological study; Other: pharmacogenomic studies

• Registration Number: NCT00769288
• Lead Sponsor: National Cancer Institute (NCI)

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 Timeline

• Study First Submitted: 2008-10-08
• Study First Submitted QC: 2008-10-08
• Study First Posted: 2008-10-09
• Study Start: 2009-07
• Primary Completion: 2013-12
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-06
• Last Update Posted: 2014-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
I	2'-F-ara-deoxyuridine	Patients will receive a 1-hour infusion of FAU on days 1-5.
I	positron emission tomography	Patients will receive a 1-hour infusion of FAU on days 1-5.
I	laboratory biomarker analysis	Patients will receive a 1-hour infusion of FAU on days 1-5.
I	pharmacological study	Patients will receive a 1-hour infusion of FAU on days 1-5.
I	pharmacogenomic studies	Patients will receive a 1-hour infusion of FAU on days 1-5.

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
Clinical response to FAU, evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee	Up to 30 days	Response will be described by point estimates and exact confidence intervals.
Pharmacokinetics of FAU, including Cmax, Tmax, AUC 0-last, AUC 0-infinity, CL, t1/2, and Vss	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.

Trial Locations

Locations (1)

Wayne State University; 🇺🇸 Detroit, Michigan, United States