Clinical trial NCT00248404: NB1011 Administered by Continuous Infusion in Cancers That Overexpress Thymidylate Synthase (TS)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Tumors
Keywords: 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
Lead sponsor: Kiadis Pharma
Sponsor class: INDUSTRY
First posted: 2005-11-04
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Safety/tolerability of NB1011 infusions
measure: Determination of maximum tolerated dose (MTD)
Secondary outcomes:
measure: Pharmacokinetics of NB1011 and its metabolite
measure: Clinical activity as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
measure: Assessment of TS overexpression
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
References:
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.
citation: 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.
citation: 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. doi: 10.1200/JCO.1996.14.1.176.
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 Orleans, June 4-8, 2004 (abstract 3144)