Bevacizumab and Polyethyleneglycol-7-Ethyl-10-Hydroxycamptothecin in Treating Patients With Refractory Solid Tumors

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01301547
First received: February 18, 2011
Last updated: NA
Last verified: February 2011
History: No changes posted

February 18, 2011
February 18, 2011
November 2010
September 2011   (final data collection date for primary outcome measure)
Proportion of patients whose expression of HIF-1α protein declines by 50% compared to baseline [ Designated as safety issue: No ]
Same as current
No Changes Posted
  • Safety and tolerability of bevacizumab and EZN-2208 [ Designated as safety issue: Yes ]
  • Response to bevacizumab and EZN-2208 [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Bevacizumab and Polyethyleneglycol-7-Ethyl-10-Hydroxycamptothecin in Treating Patients With Refractory Solid Tumors
A Pilot Study of Weekly EZN-2208 (PEGylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as polyethyleneglycol-7-ethyl-10-hydroxycamptothecin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with polyethyleneglycol-7-ethyl-10-hydroxycamptothecin may be an effective treatment for solid tumors.

PURPOSE: This clinical trial is studying how well giving bevacizumab together with polyethyleneglycol-7-ethyl-10-hydroxycamptothecin works in treating patients with refractory solid tumors.

OBJECTIVES:

Primary

  • 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).

Secondary

  • 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.

Interventional
Not Provided
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • Biological: bevacizumab
  • Drug: polyethyleneglycol-7-ethyl-10-hydroxycamptothecin
  • Genetic: protein expression analysis
  • Other: laboratory biomarker analysis
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
Not Provided
September 2011   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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 following:

    • 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 dissection)
      • Clinically significant peripheral vascular disease
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • 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

PRIOR CONCURRENT THERAPY:

  • 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
Both
18 Years and older
No
Not Provided
United States
 
NCT01301547
CDR0000690319, NCIDTC-P9592
Not Provided
Shivaani Kummar, NCI - Developmental Therapeutics Clinic
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Shivaani Kummar, MD NCI - Medical Oncology Branch
National Cancer Institute (NCI)
February 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP