NB1011 Administered by Continuous Infusion in Cancers That Overexpress Thymidylate Synthase (TS)

Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00248404
• Other study ID #: CR-TSC-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2005
• Est. completion date: December 12, 2007

Study information

• Verified date: May 2022
• Source: Kiadis Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Other known NCT identifiers

• NCT00255736

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: December 12, 2007
• Est. primary completion date: December 12, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Tumors

Intervention

Drug:
• NB1011

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Kiadis Pharma

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

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. — View Citation

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. — View Citation

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 Orlean

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety/tolerability of NB1011 infusions
Primary	Determination of maximum tolerated dose (MTD)
Secondary	Pharmacokinetics of NB1011 and its metabolite
Secondary	Clinical activity as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Secondary	Assessment of TS overexpression