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
  Purpose

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.


Condition Intervention
Unspecified Adult Solid Tumor, Protocol Specific
Biological: bevacizumab
Drug: polyethyleneglycol-7-ethyl-10-hydroxycamptothecin
Genetic: protein expression analysis
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Weekly EZN-2208 (PEGylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients whose expression of HIF-1α protein declines by 50% compared to baseline [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of bevacizumab and EZN-2208 [ Designated as safety issue: Yes ]
  • Response to bevacizumab and EZN-2208 [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2010
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01301547

Locations
United States, Maryland
NCI - Developmental Therapeutics Clinic Recruiting
Bethesda, Maryland, United States, 20892
Contact: Shivaani Kummar, MD    301-435-5402      
Sponsors and Collaborators
Investigators
Principal Investigator: Shivaani Kummar, MD NCI - Medical Oncology Branch
  More Information

No publications provided

Responsible Party: Shivaani Kummar, NCI - Developmental Therapeutics Clinic
ClinicalTrials.gov Identifier: NCT01301547     History of Changes
Other Study ID Numbers: CDR0000690319, NCIDTC-P9592
Study First Received: February 18, 2011
Last Updated: February 18, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
10-hydroxycamptothecin
Camptothecin
Irinotecan
Bevacizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014