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FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

Primary Purpose

Adult Grade III Lymphomatoid Granulomatosis, Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

2'-F-ara-deoxyuridine

positron emission tomography

laboratory biomarker analysis

pharmacological study

pharmacogenomic studies

About this trial

This is an interventional treatment trial for Adult Grade III Lymphomatoid Granulomatosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Wayne State University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Patients will receive a 1-hour infusion of FAU on days 1-5.

Outcomes

Primary Outcome Measures

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 Measures

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.

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.

Full Information

NCT ID

NCT00769288

First Posted

October 8, 2008

Last Updated

January 6, 2014

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00769288

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2014

Overall Recruitment Status

Completed

Study Start Date

July 2009 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Patients will receive a 1-hour infusion of FAU on days 1-5.

Intervention Type

Drug

Intervention Name(s)

2'-F-ara-deoxyuridine

Other Intervention Name(s)

FAU

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

positron emission tomography

Other Intervention Name(s)

FDG-PET, PET, PET scan, tomography, emission computed

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

pharmacological study

Other Intervention Name(s)

pharmacological studies

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

pharmacogenomic studies

Other Intervention Name(s)

Pharmacogenomic Study

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

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

Time Frame

Up to 28 days

Secondary Outcome Measure Information:

Title

Clinical response to FAU, evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee

Description

Response will be described by point estimates and exact confidence intervals.

Time Frame

Up to 30 days

Title

Pharmacokinetics of FAU, including Cmax, Tmax, AUC 0-last, AUC 0-infinity, CL, t1/2, and Vss

Description

All pharmacokinetic parameters will be summarized with standard descriptive statistics.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Patricia LoRusso

Organizational Affiliation

Wayne State University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wayne State University

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

12. IPD Sharing Statement

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FAU in Treating Patients With Advanced Solid Tumors or Lymphoma

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