Status:
COMPLETED
EZN-2208 (Pegylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors
Lead Sponsor:
National Cancer Institute (NCI)
Conditions:
Neoplasms
Eligibility:
All Genders
18-120 years
Phase:
PHASE1
Brief Summary
Background: \- The anticancer drug bevacizumab works by reducing the formation of new blood vessels in tumors, which can slow or stop the growth of cancer cells and supporting blood vessels. The expe...
Detailed Description
Background One reason postulated for the limited efficacy of anti-angiogenic or anti-VEGF agents such as bevacizumab is that they cause intra-tumoral hypoxia, resulting in the induction and up-regula...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- Patients must have histologically confirmed (by the Laboratory of Pathology, NCI) solid tumors that are metastatic or unresectable and for which standard therapies do not exist or are no longer effective.
- There are no restrictions on prior therapy.
- Age greater than or equal to18 years. Because no dosing or adverse event data are currently available on the use of EZN-2208 in combination with bevacizumab in patients less than 18 years of age, children are excluded from this study, but will be eligible for future pediatric Phase I combination trials.
- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%
- Life expectancy of greater than 3 months.
- Patients must have normal organ and marrow function as defined below:
- leukocytes greater than or equal to 3,000/mcL
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin less than or equal to 1.5 times the institutional upper limit of normal
- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times the institutional upper limit of normal
- creatinine less than or equal to 1.5 times the institutional upper limit of normal
- OR
- creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
- The effects of EZN-2208 on the developing human fetus are unknown. For this reason and because bevacizumab is known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months after completion of study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
- Disease amenable to biopsy, and willingness to undergo biopsies.
- EXCLUSION CRITERIA:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients must be (Bullet) 2 weeks since receiving study drug as a participant in a Phase 0 study (also referred to as an early Phase I study where a subtherapeutic dose of drug is administered).
- Patients may not be receiving any other investigational agents.
- Patients with a diagnosis of colorectal cancer, who have previously failed treatment with a topoisomerase I inhibitor. Patients with all other types of malignancies will be considered for eligibility regardless of prior exposure to topoisomerase 1 inhibitors.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to EZN-2208 or bevacizumab.
- Uncontrolled intercurrent illness including, but not limited to, clinically significant cardiovascular disease as defined below, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because bevacizumab is an antiangiogenic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with EZN-2208, breastfeeding should be discontinued if the mother is treated with EZN-2208.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with EZN-2208. In addition, these patients are at increased risk of lethal infections when treated with marrowsuppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Urine protein should be screened by urine analysis. If protein is 2+ or higher, 24-hour urine protein should be obtained and the level should be \<1000 mg for patient enrollment.
- Serious or non-healing wound, ulcer, or bone fracture. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
- Invasive procedures defined as follows:
- Major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days.
- Anticipation of need for major surgical procedures during the course of the study.
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months.
- Known CNS disease except for treated brain metastasis. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (MRI or CT). Patients receiving EIAED anticonvulsants will not be eligible to participate (Appendix B). Patients on non-EIAED may be enrolled at the discretion of the PI. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent), or a combination as deemed appropriate by the treating physician.
- Patients with clinically significant cardiovascular disease are excluded:
- Inadequately controlled hypertension (systolic blood pressure \>160 mm Hg and/or diastolic blood pressure \>90 mm Hg despite antihypertensive medication)
- History of stroke/cerebrovascular accident within 6 months
- Myocardial infarction or unstable angina within 6 months
- New York Heart Association grade II or greater congestive heart failure
- Serious and inadequately controlled cardiac arrhythmia
- Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)
- Clinically significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic anticoagulation will be excluded.
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
Exclusion
Key Trial Info
Start Date :
November 15 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 23 2014
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT01251926
Start Date
November 15 2010
End Date
April 23 2014
Last Update
November 15 2019
Active Locations (1)
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1
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892