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AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00243061
Recruitment Status : Completed
First Posted : October 21, 2005
Results First Posted : June 23, 2015
Last Update Posted : August 27, 2018
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE October 20, 2005
First Posted Date  ICMJE October 21, 2005
Results First Submitted Date  ICMJE July 9, 2014
Results First Posted Date  ICMJE June 23, 2015
Last Update Posted Date August 27, 2018
Study Start Date  ICMJE January 2006
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2015)
  • Objective Tumor Response (Partial or Complete Response) According to RECIST [ Time Frame: Up to 6 years ]
    Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [J Nat Cancer Inst 92(3):205-216, 2000]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions, assessed by CT or 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."
  • Prolonged Stable Disease According to RECIST [ Time Frame: Up to 6 months ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00243061 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2018)
  • Median Survival Time [ Time Frame: Up to 6 years ]
  • Survival Rate [ Time Frame: At 1 year ]
  • Response Duration [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 6 years ]
  • Stable Disease Duration [ Time Frame: From the start of the treatment until the criteria for progression are met, assessed up to 6 years ]
  • Highest Toxicity Grade Assessed by NCI CTCAE Version 3.0 [ Time Frame: Up to 6 years after completion of treatment ]
  • Time to Disease Progression [ Time Frame: Up to 6 years ]
  • Clinical Benefit Response [ Time Frame: Up to 6 years ]
  • Changes in Levels of Soluble Angiogenic Factors [ Time Frame: From baseline to up to 6 years ]
  • Change in Vessel Permeability and Blood Flow by DCE-MRI [ Time Frame: From baseline to up to 28 days after starting daily oral dosing ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma
Official Title  ICMJE A Phase II Study of AZD2171 in Previously Untreated Patients With Metastatic or Recurrent Malignant Melanoma
Brief Summary This phase II trial is studying how well AZD2171 works in treating patients with recurrent or stage IV melanoma. AZD2171 may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.
Detailed Description


I. To assess the objective tumor response rate of AZD2171 administered to patients with recurrent or metastatic malignant melanoma.

II. To assess the toxicity, median survival time, 1-year survival rate, response or stable disease duration, time to disease progression and clinical benefit response of AZD2171 administered to patients with recurrent or metastatic malignant melanoma.

III. To measure baseline and post-treatment levels of angiogenic growth factors and receptors, as well as circulating endothelial cells, and to explore the relationship between these potential correlative endpoints and 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 explore the relationship between these potential imaging endpoints and clinical outcome.

V. To look for polymorphisms of kdr/flk-1, and other genes in this pathway, by performing pharmacogenetic analysis of pbmc's, and correlate genotype with VEGF levels and response to therapy.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral AZD2171 once daily 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 for survival.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acral Lentiginous Malignant Melanoma
  • Ciliary Body and Choroid Melanoma, Medium/Large Size
  • Ciliary Body and Choroid Melanoma, Small Size
  • Extraocular Extension Melanoma
  • Intraocular Melanoma
  • Iris Melanoma
  • Lentigo Maligna Malignant Melanoma
  • Recurrent Melanoma
  • Stage, Intraocular Melanoma
  • Stage IV Melanoma
  • Superficial Spreading Malignant Melanoma
Intervention  ICMJE Drug: cediranib maleate
Given orally
Other Name: AZD2171
Study Arms  ICMJE Experimental: Treatment (cediranib maleate)
Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Drug: cediranib maleate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 1, 2015)
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically/cytologically confirmed recurrent/metastatic malignant melanoma (stage IV acral lentiginous, lentigo maligna, superficial spreading or ocular malignant melanoma)
  • Measurable disease- at least 1 lesion accurately measured in at least 1 dimension (longest diameter) as >=20mm with conventional techniques or >=10mm with spiral CT scan

    • Previously irradiated lesions not considered measurable unless they demonstrated progression prior to study entry
  • No prior chemotherapy (including regional therapy); prior adjuvant immunotherapy permitted if completed >3 months prior to study entry; patients may have received prior radiation therapy if completed >=4 weeks prior to study entry

    • Previous surgery permissible if performed >=4 weeks prior to study entry
  • Life expectancy >12 weeks
  • ECOG performance status=< 2 (Karnofsky>=60%)
  • Leukocytes>=3,000/mcL
  • Absolute neutrophil count>=1,500/mcL
  • Platelets>=100,000/mcL
  • Hemoglobin>=8g/dL
  • Total bilirubin<1.5x institutional ULN (IULN)
  • AST/ALT=<3 x IULN (5xULN if liver metastases)
  • Creatinine within IULN
  • Creatinine within IULN OR
  • Creatinine clearance>=60mL/min/m^2 if creatinine levels above IULN
  • Baseline blood pressure <140/90mmHg; may be taking antihypertensive medications
  • AZD2171 has shown to terminate fetal development in rat as expected for process dependent on VEGF signaling; women of childbearing potential must have negative pregnancy test prior to study entry; women of childbearing potential/men must agree to use adequate contraception (hormonal/barrier method of birth control; abstinence) prior to study entry and for duration of study
  • Ability to understand/willingness to sign written informed consent

Exclusion Criteria:

  • Any previous chemotherapy or immunotherapy for recurrent/metastatic disease; patients who have had radiotherapy or major surgery within 4 weeks prior to entering study or those who have not recovered from AEs due to treatment received more than 4 weeks earlier
  • May not be concurrently receiving other investigational agents nor have participated in an investigational trial of bio-, chemo- or immunotherapy agents
  • Known brain metastases because of their poor prognosis and because patients often develop progressive neurologic dysfunction that would confound evaluation of neurologic and other AEs
  • History of allergic reactions attributed to compounds of similar chemical/biologic composition to AZD2171
  • Mean QTc>470msec (Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome
  • >+1 proteinuria on 2 consecutive dipsticks taken no less than 1 week apart
  • Uncontrolled intercurrent illness including but not limited to hypertension, ongoing/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 excluded from study because AZD2171 is a VEGF inhibitor with known abortifacient effects; breastfeeding should be discontinued if mother is treated with AZD2171
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of potential for PK interactions with AZD2171; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Any significant abnormality noted in ECG within 14 days of treatment
  • A NYHA 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/biologics with proarrhythmic potential; these drugs are prohibited during studies with AZD2171
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries United States
Administrative Information
NCT Number  ICMJE NCT00243061
Other Study ID Numbers  ICMJE NCI-2012-03026
PHL-038 ( Other Grant/Funding Number: N01CM62203 )
N01CM62203 ( U.S. NIH Grant/Contract )
N01CM62201 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Elaine McWhirter Princess Margaret Hospital Phase 2 Consortium
PRS Account National Cancer Institute (NCI)
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP