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: May 7, 2013
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 IV Intraocular Melanoma
Stage IV Melanoma
Superficial Spreading Malignant Melanoma
Drug: cediranib maleate
Other: laboratory biomarker analysis
Procedure: dynamic contrast-enhanced magnetic resonance imaging
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 ]
  • 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: 33
Study Start Date: January 2006
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 Names:
  • AZD2171
  • Recentin
Other: laboratory biomarker analysis
Correlative studies
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Correlative studies
Other Name: DCE-MRI

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:

  • Patients must have histologically or cytologically confirmed recurrent or metastatic malignant melanoma (stage IV acral lentiginous, lentigo maligna, superficial spreading or ocular malignant melanoma)
  • 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 CT scan

    • Previously irradiated lesions are not considered measurable, unless they have demonstrated progression prior to study entry
  • Patients must not have had any prior chemotherapy (including regional therapy); prior adjuvant immunotherapy is 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 is permissible, if performed >= 4 weeks prior to study entry
  • Life expectancy of greater than 12 weeks
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8 g/dL
  • Total bilirubin < 1.5 x institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal (5 x ULN if liver metastases)
  • Creatinine within institutional normal limits
  • Creatinine within institutional normal limits OR
  • Creatinine clearance >= 60 mL/min/m^2 for patients with creatinine levels above institutional normal
  • Baseline blood pressure must be < 140/90mmHg; patients may be taking antihypertensive medications
  • AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on 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 any previous chemotherapy, or immunotherapy for recurrent/metastatic disease; 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 due to treatment received more than 4 weeks earlier
  • Patients may not be concurrently receiving any other investigational agents nor have participated in an investigational trial of bio-, chemo- or immunotherapy agents
  • Patients with known brain metastases will 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 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; breastfeeding should be discontinued if the mother is treated with AZD2171
  • 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 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: 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
Last Updated: May 7, 2013
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 October 30, 2014