Clinical trial NCT00466583: Phase 1 Study of EZN-2968 Weekly in Adult Patients With Advanced Solid Tumors or Lymphoma
Official title: A Phase 1, Open-Label, Dose Escalation Study Evaluating the Safety and Tolerability of EZN-2968, a Locked Nucleic Acid Antisense Oligonucleotide Against Hypoxia-Inducible Factor-1α, Administered as a Weekly 2-Hour Intravenous Infusion in Adult Patients With Advanced Solid Tumors or Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma
Lymphoma
Keywords: Carcinoma, Lymphoma
Lead sponsor: Enzon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2007-04-27
Enrollment: 52
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: This is a Phase 1, open-label, non-randomized, dose-escalation study to determine the maximum tolerated dose (MTD), safety, tolerance, and pharmacologic profile of EZN-2968, a locked nucleic acid antisense oligonucleotide against hypoxia-inducible factor 1α administered as a 2-hour intravenous (i.v.) infusion weekly for 3 weeks per 6-week cycle. In patients treated at a recommended Phase 2 dose of EZN-2968, dose intensification will proceed by maintaining the dose, but gradually increasing the number of doses per 6-week cycle. Up to 3 intensification cohorts will receive the recommended Phase 2 dose of EZN-2968.

Detailed description: This is a Phase 1, open-label, non-randomized, dose-escalation study to determine the maximum tolerated dose (MTD), safety, tolerance, and pharmacologic profile of EZN-2968, a locked nucleic acid antisense oligonucleotide against hypoxia-inducible factor 1α (anti-HIF-1α LNA AS ODN) administered as a 2-hour intravenous (i.v.) infusion weekly for 3 weeks per 6-week cycle. In patients treated at a recommended Phase 2 dose of EZN-2968, dose intensification will proceed by maintaining the dose, but gradually increasing the number of doses per 6-week cycle. Up to 3 intensification cohorts will receive the recommended Phase 2 dose of EZN-2968.

Eligibility criteria: Inclusion Criteria: Patients must meet all of the following criteria to be eligible for enrollment into the study.

* Histologically or cytologically confirmed diagnosis of advanced and/or metastatic solid tumor or lymphoma (Hodgkin's or non-Hodgkin's)
* Patients who have failed standard therapy and have no known effective therapy available to them
* Patients may have a tumor amenable to biopsy
* Measurable or evaluable disease.
* Age 18 years or older

Exclusion Criteria: Patients meeting any of the following exclusion criteria will not be eligible for enrollment.

* Concurrent serious medical illness
* Known, clinically suspected, or history of central nervous system (CNS) tumor involvement
* Prior chemotherapy, immunotherapy, investigational agent, or other therapy used to treat the cancer within 4 weeks (6 weeks for prior treatment with mitomycin C or nitrosoureas) before the scheduled administration of EZN-2968. Luteinizing hormone-releasing hormone (LHRH) agonist therapy is permitted for patients with hormone refractory prostate cancer.

Primary outcomes:
measure: Determine the maximum tolerated dose (MTD) of EZN-2968.
timeFrame: January 2011
Secondary outcomes:
measure: Determine the pharmacokinetic (PK) profile; Determine the PD profile.
timeFrame: June 2011
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
Study officials:
affiliation: Fox Chase Cancer Center
name: Anthony Olszanski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Herbert Hurwitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Joe Arrington Cancer Center
name: Jose Figueroa, MD
role: PRINCIPAL_INVESTIGATOR
References: