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A Pilot Study of Weekly EZN-2208 (PEGylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors

18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Pilot Study of Weekly EZN-2208 (PEGylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors



- Determine the modulation of HIF-1α protein (by ELISA) in patients with refractory solid
tumors after treatment with bevacizumab and
polyethyleneglycol-7-ethyl-10-hydroxycamptothecin (EZN-2208).


- Determine the safety and tolerability of bevacizumab and EZN-2208 in these patients.

- Perform correlative studies (DCE-MRI and soluble markers) to assess changes in
angiogenesis in tumor tissue. (exploratory)

- Evaluate antitumor responses as determined by RECIST.

OUTLINE: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 (day -7 of
course 1 only) and polyethyleneglycol-7-ethyl-10-hydroxycamptothecin IV over 60 minutes on
days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Patients undergo blood sample collection and tumor biopsies at baseline and during study for
HIF-1α protein expression and other correlative studies.

After completion of study therapy, patients are followed up for 28 days.

Inclusion Criteria


- Histologically confirmed solid tumors

- Metastatic or unresectable disease for which standard therapies do not exist or
are no longer effective

- No known CNS disease

- Treated brain metastasis not requiring steroids and with no evidence of
progression or hemorrhage after treatment for ≥ 3 months, as ascertained by
clinical examination and brain imaging (MRI or CT scan), allowed

- 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


- ECOG performance status 0-2 (Karnofsky 60-100%)

- Life expectancy > 3 months

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Urine protein: proteinuria 2+ OR < 1,000 mg on 24-hour urine collection

- Fertile patients must use effective contraception (hormonal, barrier method of birth
control, or abstinence) prior to, during, and for 3 months after completion of study

- Not pregnant or nursing

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to polyethyleneglycol-7-ethyl-10-hydroxycamptothecin (EZN-2208)
or bevacizumab

- No uncontrolled intercurrent illness including, but not limited to, any of the

- Clinically significant cardiovascular disease

- Inadequately controlled hypertension (systolic BP > 160 mm Hg and/or
diastolic BP > 90 mm Hg despite antihypertensive medication)

- History of stroke and/or cerebrovascular accident within the past 6 months

- Myocardial infarction or unstable angina within the past 6 months

- NYHA grade II-IV congestive heart failure

- Serious and inadequately controlled cardiac arrhythmia

- Significant vascular disease (e.g., aortic aneurysm, history of aortic

- Clinically significant peripheral vascular disease

- Psychiatric illness/social situations that would limit compliance with study

- No serious or non-healing wound, ulcer, or bone fracture

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 6 months

- No significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
recent peripheral arterial thrombosis) within the past 6 months

- No evidence of bleeding diathesis or coagulopathy

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies


- More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas
or mitomycin C) and recovered

- There are no restrictions on prior therapy

- At least 2 weeks since receiving study drug as a participant in a phase 0 study
(or early phase I)

- No major surgical procedure, open biopsy, or significant traumatic injury within the
past 28 days, and no anticipation of need for major surgical procedures during the
course of the study

- No other concurrent investigational agents

- No other concurrent chemotherapy

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent enzyme-inducing anti-epileptic drugs (EIAED)

- Patients on non-EIAED allowed at the discretion of principal investigator

- No concurrent anticoagulation therapy

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients whose expression of HIF-1α protein declines by 50% compared to baseline

Safety Issue:


Principal Investigator

Shivaani Kummar, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Medical Oncology Branch



Study ID:




Start Date:

November 2010

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms



NCI - Developmental Therapeutics ClinicBethesda, Maryland  20892