Cediranib Maleate in Treating Patients With Recurrent or Persistent Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01132820
First received: May 27, 2010
Last updated: June 11, 2013
Last verified: March 2013
  Purpose

This phase II trial is studying the side effects and how well cediranib maleate works in treating patients with persistent or recurrent endometrial cancer. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor


Condition Intervention Phase
Endometrial Adenocarcinoma
Endometrial Adenosquamous Cell Carcinoma
Endometrial Clear Cell Carcinoma
Endometrial Papillary Serous Carcinoma
Recurrent Endometrial Carcinoma
Drug: cediranib maleate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Cediranib (Recentin; AZD2171, IND# 72740, NSC# 732208) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
  • Objective tumor response according to RECIST v. 1.1. [ Time Frame: Within 6 months ] [ Designated as safety issue: No ]
  • Adverse effects as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • PFS according to RECIST v. 1.1 [ Time Frame: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Response without regard to the time of documented response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: June 2010
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cediranib maleate)
Patients receive oral cediranib maleate once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate
Given PO
Other Names:
  • AZD2171
  • Recentin
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the response at 6 months of patients with persistent or recurrent endometrial carcinoma treated with cediranib maleate.

II. To determine the progression-free survival at 6 months of patients treated with this regimen.

III. To determine the frequency and degree of toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival of patients treated with this regimen.

II. To determine the duration of overall survival of patients treated with this regimen.

III. To estimate the probability of response without restriction on the duration of response documentation of these patients since study enrollment.

TERTIARY OBJECTIVES:

I. To determine whether the response to cediranib maleate correlates with high-expression of its receptor targets (e.g., VEGFR [1, 2, 3] and PDGFR).

II. To determine whether the response to cediranib maleate correlates with high endogenous circulating plasma levels of VEGFA, low-levels of its endogenous inhibitor, sFlt-1 (the truncated, circulating portion of VEGFR-1), or circulating Tissue Factor (TF) or circulating Par-4, both potential markers of tumor progression.

III. To determine whether a high-expression of VEGFA on pre-treatment tumor specimens correlates with response to this regimen.

IV. To determine whether expression of phosphorylated ERK1 and 2, c-Jun, Stat3, PKC, and p70S6 kinase correlates with resistance or sensitivity to cediranib maleate.

OUTLINE: This is a multicenter study.

Patients receive oral cediranib maleate once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker and other analysis.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed primary endometrial carcinoma including any of the following epithelial cell types:

    • Endometrioid adenocarcinoma
    • Serous adenocarcinoma
    • Undifferentiated carcinoma
    • Clear cell adenocarcinoma
    • Mixed epithelial carcinoma
    • Adenocarcinoma not otherwise specified
    • Mucinous adenocarcinoma
    • Squamous cell carcinoma
    • Transitional cell carcinoma
  • Recurrent or persistent disease

    • Refractory to curative therapy or established treatments
  • Measurable disease defined as >= 1 lesion that can be accurately measured in >= 1 dimension (longest diameter to be recorded)

    • Lesion must be >= 10 mm by CT scan, MRI, or caliper measurement by clinical exam OR >= 20 mm by chest x-ray
    • Lymph nodes must be > 15 mm in short axis by CT scan or MRI
  • Patient must have >= 1 "target lesion" to assess response as defined by RECIST v. 1.1

    • Tumors within a previous irradiated field are designated as non-target lesions unless progression is documented OR a biopsy is obtained to confirm persistence of disease >= 90 days after completion of radiotherapy
  • Patient must not be eligible for a higher priority GOG protocol, if one exists
  • Must have had 1 prior chemotherapeutic regimen for management of endometrial cancer that may include 1 of the following:

    • Chemotherapy
    • Chemotherapy and radiotherapy

      • Chemotherapy in conjunction with primary radiotherapy as a radio-sensitizer will be counted as a systemic chemotherapy regimen
    • Consolidation and/or maintenance therapy
  • No CNS disease, including primary brain tumor or brain metastases
  • GOG performance status (PS) 0-2 (for patients who received 1 prior therapeutic regimen) OR GOG PS 0-1 (for patients who received 2 prior regimens)
  • ANC >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Creatinine =< 1.5 times upper limit of normal (ULN) OR creatinine clearance >= 60 mL/min
  • Urine protein: creatinine (UPC) ratio < 1.0 g
  • Bilirubin =< 1.5 times ULN
  • AST =< 2.5 times ULN
  • Alkaline phosphatase =< 2.5 times ULN
  • INR =< 1.5 times ULN (between 2 and 3 for patients on stable dose of therapeutic warfarin)
  • PTT =< 1.5 times ULN
  • Amylase and lipase normal
  • Thyroid stimulation hormone (TSH) and free thyroxine (Free T4) normal
  • Peripheral neuropathy (sensory and motor) =< grade 1
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No active infection requiring antibiotics

    • Uncomplicated urinary tract infection allowed
  • No invasive malignancies within the past 3 years except nonmelanoma skin cancer or curatively treated localized cancer of the breast, head and neck, or skin
  • No serious non-healing wound, ulcer, or bone fracture, including the following:

    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No active bleeding or pathological conditions that carry high-risk of bleeding, including the following:

    • Known bleeding disorder
    • Coagulopathy disorder
    • Tumor involving major vessels
  • No uncontrolled seizures with standard medical therapy
  • No clinically significant cardiovascular disease including, but not limited to, any of the following:

    • Uncontrolled hypertension (defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 100 mm Hg despite optimized antihypertensive therapy)
    • Myocardial infarction or unstable angina within the past 6 months
    • New York Heart Association (NYHA) grade II-IV congestive heart failure or serious cardiac arrhythmia requiring medication

      • Patients who received prior anthracycline treatment, including doxorubicin hydrochloride and/or liposomal doxorubicin, and have an ejection fraction < normal are not eligible for this study
    • Peripheral vascular disease >= grade 2 as assessed by NCI CTCAE
    • History of cerebrovascular accident (CVA, stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
    • Mean QTc > 500 msec or history of familial long QT syndrome
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • No concurrent amifostine or other protective reagents
  • Recovered from recent surgery, radiotherapy, or chemotherapy
  • At least 1 week since prior hormonal therapy directed at the malignant tumor
  • At least 3 weeks since any other prior anticancer therapy
  • One prior cytotoxic regimen for management of recurrent or persistent disease allowed

    • Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
  • No prior non-cytotoxic chemotherapy for management of recurrent or persistent disease

    • Prior hormonal therapy allowed
  • No prior cediranib maleate or other VEGF pathway-targeted therapy
  • No prior cancer treatment that contraindicates this protocol therapy
  • No prior radiotherapy to any portion of the abdominal cavity or pelvis within the past 3 years other than treatment for endometrial cancer

    • Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed provided it was completed > 3 years and patient remains free of recurrent or metastatic disease
  • No prior chemotherapy for any abdominal or pelvic tumor other than for endometrial cancer within the past 5 years

    • Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years and patient remains free of recurrent or metastatic disease
  • No major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days
  • No anticipation of major surgical procedure during the course of the study
  • No minor surgical procedures, fine needle aspirates, or core biopsies within the past 7 days
  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: NCT01132820

  Hide Study Locations
Locations
United States, California
Providence Saint Joseph Medical Center
Burbank, California, United States, 91505
Palo Alto Medical Foundation-Gynecologic Oncology
Mountain View, California, United States, 94040
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102
The Hospital of Central Connecticut
New Britain, Connecticut, United States, 06050
United States, Florida
Sarasota Memorial Hospital
Sarasota, Florida, United States, 34239
United States, Georgia
Central Georgia Gynecologic Oncology
Macon, Georgia, United States, 31201
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sudarshan K Sharma MD Limted-Gynecologic Oncology
Hinsdale, Illinois, United States, 60521
United States, Indiana
Saint Vincent Oncology Center
Indianapolis, Indiana, United States, 46260
United States, Iowa
Mercy Cancer Center-West Lakes
Clive, Iowa, United States, 50325
Medical Oncology and Hematology Associates-West Des Moines
Clive, Iowa, United States, 50325
Iowa Oncology Research Association CCOP
Des Moines, Iowa, United States, 50309
Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Medical Oncology and Hematology Associates
Des Moines, Iowa, United States, 50314
Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa, United States, 50309
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
Mercy Medical Center-West Lakes
West Des Moines, Iowa, United States, 50266
Methodist West Hospital
West Des Moines, Iowa, United States, 50266-7700
United States, Kansas
Cancer Center of Kansas - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas - El Dorado
El Dorado, Kansas, United States, 67042
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, United States, 66701
Cancer Center of Kansas-Independence
Independence, Kansas, United States, 67301
Cancer Center of Kansas-Kingman
Kingman, Kansas, United States, 67068
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Cancer Center of Kansas-Liberal
Liberal, Kansas, United States, 67901
Cancer Center of Kansas - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas - Pratt
Pratt, Kansas, United States, 67124
Cancer Center of Kansas - Salina
Salina, Kansas, United States, 67401
Cancer Center of Kansas - Wellington
Wellington, Kansas, United States, 67152
Wichita CCOP
Wichita, Kansas, United States, 67214
Associates In Womens Health
Wichita, Kansas, United States, 67208
Cancer Center of Kansas-Wichita Medical Arts Tower
Wichita, Kansas, United States, 67208
Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Cancer Center of Kansas - Main Office
Wichita, Kansas, United States, 67214
Cancer Center of Kansas - Winfield
Winfield, Kansas, United States, 67156
United States, Maine
Maine Medical Center-Bramhall Campus
Portland, Maine, United States, 04102
United States, Maryland
Franklin Square Hospital Center
Baltimore, Maryland, United States, 21237
Greater Baltimore Medical Center
Baltimore, Maryland, United States, 21204
United States, Michigan
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
Borgess Medical Center
Kalamazoo, Michigan, United States, 49001
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
University of Missouri - Ellis Fischel
Columbia, Missouri, United States, 65203
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
Springfield, Missouri, United States, 65802
Cox Medical Center
Springfield, Missouri, United States, 65807
Saint John's Hospital
Springfield, Missouri, United States, 65804
United States, Nebraska
Methodist Estabrook Cancer Center
Omaha, Nebraska, United States, 68114
United States, Nevada
Women's Cancer Center of Nevada
Las Vegas, Nevada, United States, 89169
United States, New Jersey
Cooper Hospital University Medical Center
Camden, New Jersey, United States, 08103
The Women's Institute for Gynecologic Cancer and Special Pelvic Surgery
Phillipsburg, New Jersey, United States, 08865
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
Kettering Medical Center
Kettering, Ohio, United States, 45429
Lake University Ireland Cancer Center
Mentor, Ohio, United States, 44060
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Cancer Care Associates-Yale
Tulsa, Oklahoma, United States, 74136-1929
United States, Pennsylvania
Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
United States, Rhode Island
Women and Infants Hospital
Providence, Rhode Island, United States, 02905
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
PeaceHealth Medical Group PC
Bellingham, Washington, United States, 98226
Harrison Medical Center
Bremerton, Washington, United States, 98310
Harrison Bremerton Hematology and Oncology
Bremerton, Washington, United States, 98310
Providence Regional Cancer Partnership
Everett, Washington, United States, 98201
Skagit Valley Hospital Regional Cancer Care Center
Mount Vernon, Washington, United States, 98274
Harrison Poulsbo Hematology and Oncology
Poulsbo, Washington, United States, 98370
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
University of Washington Medical Center
Seattle, Washington, United States, 98195
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Group Health Cooperative
Seattle, Washington, United States, 98112
Northwest Hospital
Seattle, Washington, United States, 98133
Pacific Gynecology Specialists
Seattle, Washington, United States, 98104
Swedish Medical Center-First Hill
Seattle, Washington, United States, 98122-4307
Olympic Medical Cancer Care Center
Sequim, Washington, United States, 98384
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Rockwood Cancer Treatment Center
Spokane, Washington, United States, 99204
Tacoma General Hospital
Tacoma, Washington, United States, 98405
Saint Joseph Medical Center
Tacoma, Washington, United States, 98405
Providence Saint Mary Regional Cancer Center
Walla Walla, Washington, United States, 99362
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801
Sponsors and Collaborators
Investigators
Principal Investigator: David Bender Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01132820     History of Changes
Other Study ID Numbers: NCI-2011-02043, GOG-0229J, U10CA027469
Study First Received: May 27, 2010
Last Updated: June 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Adenosquamous
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Cystadenocarcinoma, Serous
Endometrial Neoplasms
Uterine Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Maleic acid
Cediranib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 19, 2014