NB1011 Administered by Continuous Infusion in Cancers That Overexpress Thymidylate Synthase (TS) - Full Text View

Purpose

The purpose of this trial is to assess the tolerability and safety of NB1011 in the treatment of patients with cancers that overexpress TS, such as ovarian, gastrointestinal, colorectal, bladder, breast, and lung cancers.

Condition	Intervention	Phase
Tumors	Drug: NB1011	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Study of NB1011 Administered Intravenously by Continuous Infusion in an Every Second Week Regimen With Open-label Continuation in Cancers That Overexpress the Enzyme Thymidylate Synthase

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Cancer Lung Cancer

U.S. FDA Resources

Further study details as provided by Kiadis Pharma:

Primary Outcome Measures:

Safety/tolerability of NB1011 infusions
Determination of maximum tolerated dose (MTD)

Secondary Outcome Measures:

Pharmacokinetics of NB1011 and its metabolite
Clinical activity as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Assessment of TS overexpression

Estimated Enrollment:	155
Study Start Date:	September 2005

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Advanced, recurrent, or metastatic solid tumors
TS overexpression (> 4 by reverse transcription polymerase chain reaction [RT-PCR]) in archival and fresh samples
Suitable for experimental monotherapy
Measurable disease

Exclusion Criteria:

Tumors that cannot be biopsied or with low level of TS expression
Requirement for concomitant anticancer therapy
Treatment with another investigational product within 30 days of study entry
Pregnant or lactating women
Active or uncontrolled serious bacterial, viral, fungal, or parasitic infection.
HIV infection
Clinically apparent meningeal or central nervous system (CNS) metastases or carcinomatous meningitis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00248404

Locations

United States, California
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 30033
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

Kiadis Pharma

More Information

Publications:

Pegram M, Yeon CH, Ku N, Gottlieb C, Sheppard M, Cossum P, John E, Iqbal S, Garcia A, Lenz HJ. Enzyme Catalyzed Therapeutic Activation of NB1011 Selectively Targets Thymidylate Synthase-overexpressing Tumor Cells: Phase I Results. ASCO Meeting, New Orleans, June 4-8, 2004 (abstract 3144)

Neuteboom ST, Karjian PL, Boyer CR, Beryt M, Pegram M, Wahl GM, Shepard HM. Inhibition of cell growth by NB1011 requires high thymidylate synthase levels and correlates with p53, p21, bax, and GADD45 induction. Mol Cancer Ther. 2002 Apr;1(6):377-84.

Salonga D, Danenberg KD, Johnson M, Metzger R, Groshen S, Tsao-Wei DD, Lenz HJ, Leichman CG, Leichman L, Diasio RB, Danenberg PV. Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. Clin Cancer Res. 2000 Apr;6(4):1322-7.

Lenz HJ, Leichman CG, Danenberg KD, Danenberg PV, Groshen S, Cohen H, Laine L, Crookes P, Silberman H, Baranda J, Garcia Y, Li J, Leichman L. Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol. 1996 Jan;14(1):176-82.

ClinicalTrials.gov Identifier:	NCT00248404 History of Changes
Obsolete Identifiers:	NCT00255736
Other Study ID Numbers:	CR-TSC-001
Study First Received:	November 3, 2005
Last Updated:	September 26, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada

Keywords provided by Kiadis Pharma:

colorectal cancer
ovarian cancer
lung cancer
breast cancer

small bowel cancer
Advanced, recurrent, or metastatic solid tumors of any type
TS overexpression confirmed by fresh biopsy (RTPCR)
Suitable for experimental monotherapy

ClinicalTrials.gov processed this record on June 17, 2013