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

  Show 87 Study Locations
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
Endometrial Neoplasms
Carcinoma
Carcinoma, Adenosquamous
Cystadenocarcinoma, Serous
Uterine Neoplasms
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Cediranib
Maleic acid
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014