EZN-2208 (Pegylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors

Completed · Phase 1

Conditions studied: Neoplasms

In brief

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 experimental drug EZN-2208 works by limiting how well cancer cells can divide. Drugs similar to EZN-2208 also work by turning off the production of the HIF protein, which otherwise can help cancer cells to grow even when blood supply is limited. Researchers are interested in determining if EZN-2208 turns off HIF in patient tumors, and whether combining it with bevacizumab is an effective treatment for cancers that have not responded to standard treatment. Objectives: \- To assess the safety and effectiveness of the combination of EZN-2208 and bevacizumab for solid tumors that have not responded to standard treatment. Eligibility: \- Individuals at least 18 years of age who have solid tumors that have not responded to standard treatment. Design: * Participants will be screened with a full physical examination and medical history, blood and urine samples, and tumor imaging studies. * Participants will receive EZN-2208 and bevacizumab intravenously on an outpatient basis in 4-week cycles (with the exception of the first cycle, which will be 5 weeks). * Cycle 1: Participants will receive EZN-2208 once a week for 3 weeks in a row (days 1, 8, and 15), followed by 1 week without the drug. Participants will receive bevacizumab 1 week before EZN-2208 (day - 7) and then 3 weeks later (day 15). * Subsequent cycles: Participants will receive EZN-2208 once a week for 3 weeks in a row (days 1, 8, and 15), followed by 1 week without the drug. Participants will receive bevacizumab every 2 weeks (days 1 and 15). * Participants will have clinic visits with physical examinations and blood tests in the first 3 weeks of each cycle. Clinic visits may also include tumor imaging studies and tumor biopsies as directed by the study researchers. * Participants will continue to take the study drugs for as long as the tumor shrinks or does not grow, and as long as they do not experience intolerable or unsafe side effects from the drugs.

Key facts

Study ID: NCT01251926
Run by: National Cancer Institute (NCI)
People needed: 12
Starts: 2010-11-15
Expected to finish: 2014-04-23
Last updated by the study team: 2019-11-15

Who can join

Age: 18 and older, up to 120. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

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.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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