AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00243061
First received: October 20, 2005
Last updated: June 1, 2015
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: cediranib maleate
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 Study of AZD2171 in Previously Untreated Patients With Metastatic or Recurrent Malignant Melanoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective Tumor Response (Partial or Complete Response) According to RECIST [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median Survival Time [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Survival Rate [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Stable Disease Duration [ Time Frame: From the start of the treatment until the criteria for progression are met, assessed up to 6 years ] [ Designated as safety issue: No ]
  • Toxicity as Assessed by NCI CTCAE Version 3.0 [ Time Frame: Up to 6 years after completion of treatment ] [ Designated as safety issue: Yes ]
  • Time to Disease Progression [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Clinical Benefit Response [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Changes in Levels of Soluble Angiogenic Factors [ Time Frame: From baseline to up to 6 years ] [ Designated as safety issue: No ]
  • Change in Vessel Permeability and Blood Flow by DCE-MRI [ Time Frame: From baseline to up to 28 days after starting daily oral dosing ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: January 2006
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: cediranib maleate
Given orally
Other Name: AZD2171

Detailed Description:

PRIMARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00243061

Locations
Canada, Ontario
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Elaine McWhirter Princess Margaret Hospital Phase 2 Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00243061     History of Changes
Other Study ID Numbers: NCI-2012-03026, PHL-038, N01CM62203, N01CM62201
Study First Received: October 20, 2005
Results First Received: July 9, 2014
Last Updated: June 1, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hutchinson's Melanotic Freckle
Melanoma
Uveal Neoplasms
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Uveal Diseases
Cediranib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015