Clinical trial NCT00945139: Study of Bevacizumab/Doxil in Treatment of Platinum-Resistant/Refractory Ovarian Cancer (CA)
Official title: Phase II Study of Bevacizumab and Doxil in the Treatment of Platinum-Resistant or Refractory Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Lead sponsor: New Mexico Cancer Research Alliance
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: NYU Langone Health
First posted: 2009-07-23
Enrollment: 46
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Progression Free Survival (PFS) by RECIST Criteria
timeFrame: Up to 25 months
measure: Progression Free Survival (PFS) by GCIC Criteria
timeFrame: Up to 25 months
Secondary outcomes:
measure: Overall Survival
timeFrame: 4 years
measure: Overall Response Rate (ORR) by RECIST
timeFrame: 3 years
measure: Clinical Benefit Rate (by RECIST)
timeFrame: 3 years
measure: Overall Response Rate (ORR) by GCIC Criteria
timeFrame: 3 years
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Santa Fe
country: United States
facility: New Mexico Cancer Care Associates
state: New Mexico
city: New York City
country: United States
facility: New York University Cancer Institute
state: New York
Study officials:
affiliation: University of New Mexico
name: Claire F. Verschraegen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: New York University Cancer Institute
name: Franco Muggia, MD
role: STUDY_DIRECTOR
References:
citation: Verschraegen CF, Czok S, Muller CY, Boyd L, Lee SJ, Rutledge T, Blank S, Pothuri B, Eberhardt S, Muggia F. Phase II study of bevacizumab with liposomal doxorubicin for patients with platinum- and taxane-resistant ovarian cancer. Ann Oncol. 2012 Dec;23(12):3104-3110. doi: 10.1093/annonc/mds172. Epub 2012 Jul 31.