Phase 1 Study of EZN-2968 Weekly in Adult Patients With Advanced Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Carcinoma, Lymphoma

Intervention / Treatment
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* Drug: Intravenous EZN-2968 (anti-HIF-1α LNA AS-ODN)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Intravenous EZN-2968 (anti-HIF-1α LNA AS-ODN)|IV infusion of EZN 2968 given in 6 week cycles for (3 weeks on 3 weeks off) until recommended phase 2 dose identified. Up to 3 intensification cohorts will receive the recommended Phase 2 dose of EZN-2968.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose (MTD) of EZN-2968. |  | January 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the pharmacokinetic (PK) profile; Determine the PD profile. |  | June 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Lymphoma