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

Phase II Study of Bevacizumab and Doxil in the Treatment of Platinum-Resistant or Refractory Ovarian Cancer

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Doxil; Drug: Avastin

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • New Mexico Cancer Care Associates
  • New York
    • New York City, New York, United States, 10016
      • New York University Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: Bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by RECIST Criteria	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	Up to 25 months
Progression Free Survival (PFS) by GCIC Criteria	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.	Up to 25 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time from treatment initiation to death by any cause	4 years
Overall Response Rate (ORR) by RECIST	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)	3 years
Clinical Benefit Rate (by RECIST)	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	3 years
Overall Response Rate (ORR) by GCIC Criteria	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.	3 years

Collaborators and Investigators

• Sponsor: New Mexico Cancer Care Alliance
• Collaborators: Genentech, Inc.; NYU Langone Health
• Investigators: Principal Investigator: Claire F. Verschraegen, M.D., University of New Mexico; Study Director: Franco Muggia, MD, New York University Cancer Institute

Publications and helpful links

General Publications

• 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.

Helpful Links

• University of New Mexico Cancer Center
• New Mexico Cancer Care Alliance

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: July 21, 2009
• First Submitted That Met QC Criteria: July 22, 2009
• First Posted (Estimate): July 23, 2009

Study Record Updates

• Last Update Posted (Estimate): July 31, 2015
• Last Update Submitted That Met QC Criteria: July 6, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Bevacizumab; Doxorubicin
• Other Study ID Numbers: INST AVF3911s; NCI-2011-02890 (Registry Identifier: NCI CTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No