Cediranib Maleate in Treating Patients With Recurrent or Metastatic Kidney Cancer That Cannot Be Removed By Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00227760
First received: September 26, 2005
Last updated: April 7, 2014
Last verified: December 2013
  Purpose

This phase II trial studies how well cediranib maleate works in treating patients with recurrent or metastatic kidney cancer that cannot be removed by surgery. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: cediranib maleate
Other: laboratory biomarker analysis
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD2171 in Progressive Unresectable, Recurrent or Metastatic Renal Cell Carcinoma (RCC)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Incidence of durable stable disease, evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Objective response, evaluated using RECIST [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: Time from start of treatment to progression, death or last contact, or last tumor assessment before the start of further antitumor therapy, assessed up to 6.5 years ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: December 2005
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cediranib maleate)
Patients receive cediranib maleate PO QD on days 1-28. Courses repeat 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
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Correlative studies
Other Name: DCE-MRI
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the clinical benefit rate (objective response rate and rate of stable disease for at least 4 months) of AZD2171 (cediranib maleate) given to patients with progressive unresectable or, recurrent or metastatic renal cell carcinoma (RCC).

II. To assess the duration of response or stable disease, progression free, median and overall survival rates, and safety and tolerability of AZD2171.

III. To measure baseline and post treatment levels of soluble markers of angiogenic growth factors and receptors as well as levels of circulating endothelial cells, and correlate these with clinical outcome.

IV. To assess changes in blood flow and vessel permeability using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) pre and post treatment and to correlate these changes with clinical outcome.

OUTLINE:

Patients receive cediranib maleate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days 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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed renal cell cancer that is locally recurrent or metastatic and is not considered curable by standard therapy
  • 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; bone lesions are not considered to be measurable; all radiology must be performed within 28 days prior to registration
  • Previous therapy:

    • Surgery: Previous surgery is permissible; patients must be >= 4 weeks since any major surgery
    • Chemotherapy: No previous systemic chemotherapy
    • Immunotherapy: No previous therapy permitted
    • Gene/investigational therapy: No prior therapy is permitted
    • Radiation: Patients may have had radiation therapy but must have recovered from acute toxic effects prior to registration; at least 4 weeks must have elapsed since last dose of radiation before registration (exceptions may be made for low-dose, non-myelosuppressive radiotherapy); if the sole site of measurable disease is in a radiation field, there must have been documented progression at that site for patient to be eligible
  • Life expectancy of greater than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1.5 x10^9/L
  • Platelets >= 100 x10^9/L
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 × institutional ULN
  • Creatinine =< 1.5 x ULN OR creatinine clearance >= 60 mL/min/1.73 m^2
  • AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on vascular endothelial growth factor (VEGF) signaling; for this reason, 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 radiotherapy, or major surgery within 4 weeks prior to entering the study or those who have not recovered from adverse events of these therapies
  • Patients may not be receiving any other investigational agents nor have participated in an investigational trial
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171
  • Mean corrected QT interval (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 because AZD2171 is a VEGF inhibitor with known abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD2171, breastfeeding should be discontinued if the mother is treated with AZD2171
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • 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 proarrhythmic potential; these drugs are prohibited during studies with AZD2171
  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: NCT00227760

Locations
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
Ottawa, Ontario, Canada, K1Y 4E9
University Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Srikala Sridhar Princess Margaret Hospital Phase 2 Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00227760     History of Changes
Other Study ID Numbers: NCI-2013-01072, NCI-2013-01072, CDR0000446080, PHL-039, 7128, N01CM62203
Study First Received: September 26, 2005
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014