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Study of Bevacizumab/Doxil in Treatment of Platinum-Resistant/Refractory Ovarian Cancer (CA)

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
New York University School of Medicine
Information provided by (Responsible Party):
New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier:
NCT00945139
First received: July 21, 2009
Last updated: July 6, 2015
Last verified: July 2015
  Purpose
The purpose of this research study is to test the safety, tolerability, and effectiveness of two chemotherapy drugs, pegylated liposomal doxorubicin (Doxil) and bevacizumab (Avastin). How Doxil is metabolized and excreted from the body will also be studied.

Condition Intervention Phase
Ovarian Cancer
Drug: Doxil
Drug: Avastin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Bevacizumab and Doxil in the Treatment of Platinum-Resistant or Refractory Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by New Mexico Cancer Care Alliance:

Primary Outcome Measures:
  • Progression Free Survival (PFS) by RECIST Criteria [ Time Frame: Up to 25 months ] [ Designated as safety issue: No ]
    Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by hysical exam and/or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  • Progression Free Survival (PFS) by GCIC Criteria [ Time Frame: Up to 25 months ] [ Designated as safety issue: No ]
    Using GCIC criteria, progression is defined as CA-125 levels greater than, or equal to, 2 times the upper limit of a reference range on 2 occasions and at least 1 week apart.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    The time from treatment initiation to death by any cause

  • Overall Response Rate (ORR) by RECIST [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    ORR is the sum of the percentages of patients achieving complete and partial responses. Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0)

  • Clinical Benefit Rate (by RECIST) [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    Clinical Benefit Rate (CBR) is the sum of the percentages of patients achieving complete response, partial response, and stable disease. Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam and/or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  • Overall Response Rate (ORR) by GCIC Criteria [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    A response according to GCIC criteria has occurred if there is at least a 50% reduction in CA 125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they have a pretreatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment.


Enrollment: 46
Study Start Date: March 2007
Study Completion Date: August 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm: Doxil and Avastin
Patients receive both agents, doxil and Avastin.
Drug: Doxil
Open label study of Doxil given as 30 mg/m2 every three weeks by itself in cycle 1
Other Name: Doxorubicin
Drug: Avastin
First agent (Doxil) will be following by Avastin 15 mg/kg on cycle 2 and every cycle thereafter until disease progression
Other Name: Bevacizumab

Detailed Description:

Avastin:

Avastin is a humanized monoclonal antibody (a type of protein that is normally made by the immune system to help defend the body from infection and cancer). Avastin has been approved for the treatment of colorectal cancer and lung cancer. Avastin is investigational for the treatment of ovarian cancer and has not been approved by the United States Food and Drug Administration (FDA) for this use.

Avastin is thought to work by attaching to a protein called vascular endothelial growth factor (VEGF) to block its action. VEGF plays a role in the formation of both normal and abnormal blood vessels. It is present in normal tissues, but is produced in excess by most solid cancers (tumors). In cancer, VEGF helps blood vessels bring nutrients to tumor cells, allowing the tumor cells to grow. In laboratory studies with human cancer cells grown in animals, Avastin has been shown to prevent or slow the growth of different types of cancer cells by blocking the effects of VEGF.

Doxorubicin:

Doxorubicin is a type of antibiotic that is only used in cancer chemotherapy. It slows or stops the growth of cancer. Doxorubicin has been approved by the FDA to treat cancers of the head, neck, cervix, vagina, testes, prostate, uterus and Ewing's tumor.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be platinum resistant
  • Patients will be included in the study based on the following criteria:

    • No prior anthracycline use
    • PS less or equal 2
    • Lab values within certain limits (ANC greater 1000, platelets greater 100,000; ALT, AST 2 time ULN, creatinine less 2.0)
    • No more than 3 prior chemotherapy regimens, only 2 of which can have included platinum-containing regimens
    • Use of effective means of contraception in subjects of child-bearing potential

Exclusion Criteria:

  1. Disease-Specific Exclusions:

    • Evidence of complete or partial bowel obstruction
    • Need for IV hydration or TPN
    • Greater 2 prior abdominal surgeries
    • History of gastrointestinal perforation
    • Gastrointestinal perforation due to any other cause within the last 6 months
  2. General Medical Exclusions:

    • Inability to comply with study and/or follow-up procedures
    • Life expectancy of less than 12 weeks
    • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study
  3. Avastin-Specific Exclusions

    • Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or diastolic blood pressure greater 100 mmHg on antihypertensive medications)
    • Any prior history of hypertensive crisis or hypertensive encephalopathy
    • New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
    • History of myocardial infarction or unstable angina within 6 months prior to study enrollment
    • History of stroke or transient ischemic attack within 6 months prior to study enrollment
    • Known CNS disease
    • Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
    • Symptomatic peripheral vascular disease
    • Evidence of bleeding diathesis or coagulopathy
    • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
    • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
    • History of abdominal fistula, or intra-abdominal abscess within 6 months prior to study enrollment
    • Serious, non-healing wound, ulcer, or bone fracture
    • Proteinuria at screening as demonstrated by either:

      • Urine protein:creatinine (UPC) ratio 1.0 at screening OR
      • Urine dipstick for proteinuria greater or equal 2plus (patients discovered to have greater or equal 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate less or equal 1g of protein in 24 hours to be eligible)
    • Known hypersensitivity to any component of Avastin
    • Pregnant (positive pregnancy test) or lactating. No effective means of contraception (men and women) in subjects of child-bearing potential
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00945139

Locations
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87106
New Mexico Cancer Care Associates
Santa Fe, New Mexico, United States, 87505
United States, New York
New York University Cancer Institute
New York City, New York, United States, 10016
Sponsors and Collaborators
New Mexico Cancer Care Alliance
Genentech, Inc.
New York University School of Medicine
Investigators
Principal Investigator: Claire F. Verschraegen, M.D. University of New Mexico
Study Director: Franco Muggia, MD New York University Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier: NCT00945139     History of Changes
Other Study ID Numbers: INST AVF3911s  NCI-2011-02890 
Study First Received: July 21, 2009
Results First Received: June 30, 2014
Last Updated: July 6, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Bevacizumab
Liposomal doxorubicin
Doxorubicin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016