Cediranib Maleate in Treating Patients With Persistent, Recurrent, or Refractory Advanced Ovarian Epithelial, Peritoneal Cavity, or Fallopian Tube Cancer

A Phase 2 Study of AZD2171 in Recurrent or Persistent Ovarian, Peritoneal, or Fallopian Tube Cancer

This phase II trial is studying how well cediranib maleate works in treating patients with persistent, recurrent, or refractory advanced ovarian epithelial, peritoneal cavity, or fallopian tube cancer. Cediranib maleate may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

Study Overview

• Status: Completed
• Conditions: Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Fallopian Tube Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: cediranib maleate

Detailed Description

PRIMARY OBJECTIVES:

I. Objective tumor response rate (complete plus partial response plus stable disease > 16 weeks as defined by the Response Evaluation Criteria in Solid Tumors [RECIST] criteria) in women with recurrent or refractory advanced ovarian or primary peritoneal cancer.

SECONDARY OBJECTIVES:

I. Time to disease progression, median survival time, and duration of overall cancer antigen (CA)-125 response.

OUTLINE:

Patients receive cediranib maleate orally (PO) once daily (QD) every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months thereafter.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario At Kingston General Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Centre-South Street
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90033
      • University of Southern California/Norris Cancer Center
    • Pasadena, California, United States, 91105
      • City of Hope Medical Group Inc
    • Sacramento, California, United States, 95817
      • University of California at Davis Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Evanston, Illinois, United States, 60201
      • Evanston Hospital CCOP
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Peoria, Illinois, United States, 61603
      • Peoria Gynecologic Oncology
    • Peoria, Illinois, United States, 61615-7828
      • Oncology/Hematology Associates
    • Springfield, Illinois, United States, 60702
      • Central Illinois Hematology Oncology Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0944
      • University of Michigan Comprehensive Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates PLLC
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Saint John's Mercy Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has recurred or is refractory to initial therapy; patients must have received platinum-based chemotherapy before entry into this protocol
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan OR patients must have evidence of progression based on an elevated CA-125 (defined as a value of > 2 x upper limit of normal [ULN] documented on two separate determinations made > 2 weeks apart) if the physical exam is normal and CT scan of the chest/abdomen/pelvis, has a disease volume < 1 cm in maximum diameter
• Patients may have received no more than one prior chemotherapy regimen (i.e. initial first-line chemotherapy only)
• Life expectancy of greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 8 g/dL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy, radiotherapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients with borderline tumors or tumors of low malignant potential
• Patients with current bowel obstruction
• Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 30 days
• Patients with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171 (cediranib maleate)
• Mean corrected QT (QTc) > 470 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome
• Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
• Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study, breastfeeding should be discontinued if the mother is treated with AZD2171
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Any significant abnormality noted in the electrocardiogram (ECG) within 14 days of treatment
• A New York Heart Association classification of III or IV (NOTE: patients classified as class II controlled with treatment may continue with increase monitoring)
• Conditions requiring concurrent use of drugs or biologics with proarrythmic potential; these drugs are prohibited during studies with AZD2171

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: Treatment (cediranib maleate); Patients receive cediranib maleate PO QD every 4 weeks in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: cediranib maleate; 30mg given PO, daily; Other Names: AZD2171; Recentin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Benefit (Complete Response or Partial Response or Stable Disease) Based on the RECIST/Rustin Criteria	Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response(OR) = CR+PR	After 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Disease Progression	Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.	Up to 4 years
Overall Survival (OS) (Discontinued as of 4/25/2014)	The Kaplan-Meier method will be used to estimate OS. Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.	From date of radomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 32 months.
Progression-free Survival (PFS)	The Kaplan-Meier method will be used to estimate PFS. Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 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.	Time from start of treatment to time of progression, assessed up to 6 months
Duration of Overall CA-125 Response	Confirmed response on CA125 - defined as reduction in level of pre-treatment sample by > 50%.	Up to 4 years
Incidence of Toxicity Graded According to National Cancer Institution Common Terminology Criteria for Adverse Events Version 3.0		Up to 4 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Holger Hirte, Princess Margaret Hospital Phase 2 Consortium

Publications and helpful links

General Publications

• Hirte H, Lheureux S, Fleming GF, Sugimoto A, Morgan R, Biagi J, Wang L, McGill S, Ivy SP, Oza AM. A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the Princess Margaret, Chicago and California Phase II Consortia. Gynecol Oncol. 2015 Jul;138(1):55-61. doi: 10.1016/j.ygyno.2015.04.009. Epub 2015 Apr 17.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): January 15, 2018

Study Registration Dates

• First Submitted: January 16, 2006
• First Submitted That Met QC Criteria: January 16, 2006
• First Posted (Estimate): January 18, 2006

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Recurrence; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Cediranib
• Other Study ID Numbers: NCI-2012-03027 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM62201 (U.S. NIH Grant/Contract); N01CM62203 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); NCI-7129; PMH-PHL-037; PHL-037 (Other Identifier: Princess Margaret Hospital Phase 2 Consortium); 7129 (Other Identifier: CTEP)