Cediranib Maleate in Treating Patients With Recurrent or Persistent Endometrial Cancer

Endometrial Adenocarcinoma Clinical Trial

Official title:

A Phase II Evaluation of Cediranib (Recentin; AZD2171, IND#72740, NSC# 732208) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01132820
• Other study ID #: NCI-2011-02043
• Secondary ID: NCI-2011-02043GO
• Status: Completed
• Phase: Phase 2
• Start date: June 2010
• Est. completion date: January 2016

Study information

• Verified date: August 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. To assess the activity of cediranib (cediranib maleate) in patients with either persistent or recurrent endometrial carcinoma.

II. To determine the frequency and degree of toxicity of cediranib as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0 in this cohort of patients.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival and overall survival. II. To estimate the probability of response without restriction on the duration of response documentation since study enrollment.

TERTIARY OBJECTIVES:

I. To determine if the response to cediranib correlates with high-expression of its receptor targets (e.g., vascular endothelial growth factor receptor [VEGFR] [1, 2, 3] and platelet derived growth factor receptor [PDGFR]).

II. To determine if the response to cediranib correlates with high endogenous circulating plasma levels of VEGFA, low-levels of its endogenous inhibitor, soluble fms-related tyrosine kinase 3 (sFlt-1) (the truncated, circulating portion of VEGFR-1), or circulating tissue factor (TF) or circulating prostate apoptosis response-4 (Par-4), both potential markers of tumor progression.

III. To determine if a high-expression of VEGFA on pre-treatment tumor specimens correlates with response to cediranib.

IV. To determine if expression of phosphorylated mitogen activated protein kinase (ERK) 1 and 2, c-Jun, signal transducer and activator of transcription 3 (Stat3), protein kinase C (PKC), and phosphorylated ribosomal protein S6 (p70S6) kinase correlates with resistance or sensitivity to cediranib.

OUTLINE:

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

• Platelets greater than or equal to 100,000/mcl

• Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) or creatinine (Cr) clearance >= 60 ml/min

• Bilirubin less than or equal to 1.5 x upper limit of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 2.5 x ULN

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Neuropathy (sensory and motor) less than or equal to grade 1

• Urine protein creatinine (UPC) ratio must be < 1.0 gm

• If UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN

• Patients must have an amylase and lipase =< ULN

• Patients must have a thyroid stimulating hormone (TSH) level and a free thyroxine (free T4) level within the institutional normal limits

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

• Patients must meet pre-entry requirements as specified

• Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception

Exclusion Criteria:

• 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

• Patients undergoing invasive procedures as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of cediranib (AZD 2171) therapy

• Major surgical procedure anticipated during the course of the study

• Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of cediranib (AZD2171) therapy

• Patients who are pregnant or nursing

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Adenosquamous
• Endometrial Adenocarcinoma
• Endometrial Adenosquamous Carcinoma
• Endometrial Clear Cell Adenocarcinoma
• Endometrial Serous Adenocarcinoma
• Recurrent Uterine Corpus Carcinoma
• Uterine Neoplasms

Intervention

Drug:
• Cediranib Maleate
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	PeaceHealth Medical Group PC	Bellingham	Washington
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Duke University Medical Center	Durham	North Carolina
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Hartford Hospital	Hartford	Connecticut
United States	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Saint Vincent Oncology Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Central Georgia Gynecologic Oncology	Macon	Georgia
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Skagit Valley Hospital Regional Cancer Care Center	Mount Vernon	Washington
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Saint Luke's Hospital-Warren Campus	Phillipsburg	New Jersey
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Northwest Hospital	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Olympic Medical Cancer Care Center	Sequim	Washington
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Main Office	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Expression of Phosphorylated ERK1 and 2, c-Jun, Stat3, PKC, and p70S6 Kinase		Baseline
Other	Levels of Receptor Targets Such as VEGFR (1, 2, 3) and PDGFR		Baseline
Other	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
Other	VEGFA Expression on Pre-treatment Tumor Specimens	High vs low expression.	Baseline
Primary	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
Primary	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
Primary	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	Overall Survival	The observed length of life from entry into the study to death or the date of last contact.	From study entry to death or last contact, up to 5 years.
Secondary	Progression Free Survival	Time until disease progression, death, or date of last contact.	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
Secondary	Response Without Regard to the Time of Documented Response	Complete and partial tumor response by RECIST 1.1	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