Cediranib Maleate in Treating Patients With Recurrent or Persistent Endometrial Cancer

NCT01132820 | Completed Phase 2 Results DMC

• 5 other identifiers: NCI-2011-02043GOG-0229JCDR0000674008U10CA180868U10CA027469
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 87

Brief Summary

This phase II trial studies the side effects and how well cediranib maleate works in treating patients with endometrial cancer that has failed to respond to initial chemotherapy or has come back after surgery, radiation therapy, or other forms of treatment. Cediranib maleate may stop the growth of tumor cells by blocking proteins made by tumors that can stimulate growth of tumor cells as well as blood vessels in and around tumors.

Conditions

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

Outcome Measures

Primary Outcomes (3)

• Incidence of Adverse Effects as Assessed by the National Cancer Institute CTCAE v. 4.0

  Adverse Events (Grade 3 or higher)

  Up to 5 years

• Tumor Response

  Complete and Partial Tumor Response by RECIST 1.1. 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.

  For diesease evaluated by physical examination, response was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle from enrollment until stopping study therapy. The average time on study is 3 mnths

• Progression-free Survival (PFS) = > 6 Months

  Number of participants who survived for at least 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.0) 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.

  For disease evaluated by physical examination, progression was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle. Evaluated from time of enrollment until progression or death, up to 5 years

Secondary Outcomes (3)

• Overall Survival

  From study entry to death or last contact, up to 5 years.

• Progression Free Survival

  Disease that can be assessed by physical exam should be evaluated every cycle. disease assessed by imaging should be evaluated every other cycle. Time frame to determine the date of progression is from the date of enrollment up to 5 years after enrollment

• Response Without Regard to the Time of Documented Response

  Tumor responses with time restriction starts at enrollment and goes to 6 months after enrollment or until pt. off study therapy,whichever occurs first. Without time restriction starts at enrollment,lasts until off study therapy, median duration = 2.63 mth

Other Outcomes (4)

• Expression of Phosphorylated ERK1 and 2, c-Jun, Stat3, PKC, and p70S6 Kinase

  Baseline

• Levels of Receptor Targets Such as VEGFR (1, 2, 3) and PDGFR

  Baseline

• Plasma Levels of Endogenous Circulating VEGFA, Levels of Its Endogenous Inhibitor, sFlt-1 (the Truncated, Circulating Portion of VEGFR-1), Circulating TF, and Circulating Par-4

  Up to 5 years

Study Arms (1)

Treatment (cediranib maleate)

EXPERIMENTAL

Patients receive cediranib maleate PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cediranib Maleate; Other: Laboratory Biomarker Analysis

Interventions

Cediranib Maleate DRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

Treatment (cediranib maleate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cediranib maleate)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required
• Patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma
• All patients must have measurable disease; measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be \>= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or \>= 20 mm when measured by chest x-ray; lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI
• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population
• Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2; patients who have received two prior regimens must have a GOG performance status of 0 or 1
• Recovery from effects of recent surgery, radiotherapy, or chemotherapy
• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection \[UTI\])
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
• Any other prior therapy directed at the malignant tumor must be discontinued at least three weeks prior to registration
• Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen
• Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition: 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
• Note: Patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent disease, as defined above; however, due to the novel nature of biologic compounds, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy
• Patients must have NOT received any non-cytotoxic chemotherapy for management of recurrent or persistent disease; prior hormonal therapy is allowed
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

You may not qualify if:

• Patients who have had prior therapy with cediranib (AZD 2171) or other VEGF pathway-targeted therapy
• Patient with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the first date of cediranib (AZD 2171) therapy
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases
• Patients with clinically significant cardiovascular disease; this includes:
• Uncontrolled hypertension defined as systolic \> 150 mmHg or diastolic \> 100 mmHg despite optimized antihypertensive therapy
• Myocardial infarction or unstable angina within 6 months of the first date of cediranib (AZD 2171) therapy
• New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication; women who have received prior treatment with an anthracycline (including doxorubicin and/or liposomal doxorubicin) and have an ejection fraction \< institutional lower limit of normal (LLN) will be excluded from the study
• CTCAE grade 2 or greater peripheral vascular disease
• History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of cediranib (AZD 2171) therapy
• Mean corrected QT interval (QTc) \> 500 msec or history of familial long QT syndrome
• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NRG Oncology: collaborator

Study Sites (87)

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Palo Alto Medical Foundation-Gynecologic Oncology

Mountain View, California, 94040, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

Central Georgia Gynecologic Oncology

Macon, Georgia, 31201, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Sudarshan K Sharma MD Limted-Gynecologic Oncology

Hinsdale, Illinois, 60521, United States

Location

Saint Vincent Oncology Center

Indianapolis, Indiana, 46260, United States

Location

Medical Oncology and Hematology Associates-West Des Moines

Clive, Iowa, 50325, United States

Location

Mercy Cancer Center-West Lakes

Clive, Iowa, 50325, United States

Location

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Iowa-Wide Oncology Research Coalition NCORP

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates-Laurel

Des Moines, Iowa, 50314, United States

Location

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Methodist West Hospital

West Des Moines, Iowa, 50266-7700, United States

Location

Mercy Medical Center-West Lakes

West Des Moines, Iowa, 50266, United States

Location

Cancer Center of Kansas - Chanute

Chanute, Kansas, 66720, United States

Location

Cancer Center of Kansas - Dodge City

Dodge City, Kansas, 67801, United States

Location

Cancer Center of Kansas - El Dorado

El Dorado, Kansas, 67042, United States

Location

Cancer Center of Kansas - Fort Scott

Fort Scott, Kansas, 66701, United States

Location

Cancer Center of Kansas-Independence

Independence, Kansas, 67301, United States

Location

Cancer Center of Kansas-Kingman

Kingman, Kansas, 67068, United States

Location

Lawrence Memorial Hospital

Lawrence, Kansas, 66044, United States

Location

Cancer Center of Kansas-Liberal

Liberal, Kansas, 67901, United States

Location

Cancer Center of Kansas - Newton

Newton, Kansas, 67114, United States

Location

Cancer Center of Kansas - Parsons

Parsons, Kansas, 67357, United States

Location

Cancer Center of Kansas - Pratt

Pratt, Kansas, 67124, United States

Location

Cancer Center of Kansas - Salina

Salina, Kansas, 67401, United States

Location

Cancer Center of Kansas - Wellington

Wellington, Kansas, 67152, United States

Location

Associates In Womens Health

Wichita, Kansas, 67208, United States

Location

Cancer Center of Kansas-Wichita Medical Arts Tower

Wichita, Kansas, 67208, United States

Location

Cancer Center of Kansas - Main Office

Wichita, Kansas, 67214, United States

Location

Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

Wichita NCI Community Oncology Research Program

Wichita, Kansas, 67214, United States

Location

Cancer Center of Kansas - Winfield

Winfield, Kansas, 67156, United States

Location

Maine Medical Center-Bramhall Campus

Portland, Maine, 04102, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

MedStar Franklin Square Medical Center/Weinberg Cancer Institute

Baltimore, Maryland, 21237, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

University of Missouri - Ellis Fischel

Columbia, Missouri, 65212, United States

Location

Cancer Research for the Ozarks NCORP

Springfield, Missouri, 65804, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

CoxHealth South Hospital

Springfield, Missouri, 65807, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Women's Cancer Center of Nevada

Las Vegas, Nevada, 89169, United States

Location

Cooper Hospital University Medical Center

Camden, New Jersey, 08103, United States

Location

Saint Luke's Hospital-Warren Campus

Phillipsburg, New Jersey, 08865, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Lake University Ireland Cancer Center

Mentor, Ohio, 44060, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, 74146, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

PeaceHealth Medical Group PC

Bellingham, Washington, 98226, United States

Location

Harrison HealthPartners Hematology and Oncology-Bremerton

Bremerton, Washington, 98310, United States

Location

Harrison Medical Center

Bremerton, Washington, 98310, United States

Location

Providence Regional Cancer Partnership

Everett, Washington, 98201, United States

Location

Skagit Valley Hospital Regional Cancer Care Center

Mount Vernon, Washington, 98273, United States

Location

Harrison HealthPartners Hematology and Oncology-Poulsbo

Poulsbo, Washington, 98370, United States

Location

Pacific Gynecology Specialists

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Group Health Cooperative-Seattle

Seattle, Washington, 98112, United States

Location

Swedish Medical Center-First Hill

Seattle, Washington, 98122-4307, United States

Location

Northwest Hospital

Seattle, Washington, 98133, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Olympic Medical Cancer Care Center

Sequim, Washington, 98384, United States

Location

Cancer Care Northwest - Spokane South

Spokane, Washington, 99202, United States

Location

Rockwood Cancer Treatment Center-DHEC-Downtown

Spokane, Washington, 99204, United States

Location

MultiCare Tacoma General Hospital

Tacoma, Washington, 98405, United States

Location

Saint Joseph Medical Center

Tacoma, Washington, 98405, United States

Location

Providence Saint Mary Regional Cancer Center

Walla Walla, Washington, 99362, United States

Location

Wenatchee Valley Hospital and Clinics

Wenatchee, Washington, 98801, United States

Location

MeSH Terms

Interventions

cediranib

Results Point of Contact

• Title: Linda Gedeon for Michael Sill, PhD
• Organization: NRG Oncology /GOG

lgedeon@gogstats.org

716 845-1169

Study Officials

• David Bender

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2010
• First Posted: May 28, 2010
• Study Start: June 1, 2010
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: August 8, 2019
• Results First Posted: August 28, 2017

Record last verified: 2019-08

Locations

US (87)