Know Cancer

forgot password

A Phase II Study of AZD2171 in Previously Untreated Patients With Metastatic or Recurrent Malignant Melanoma

Phase 2
18 Years
Not Enrolling
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

Thank you

Trial Information

A Phase II Study of AZD2171 in Previously Untreated Patients With Metastatic or Recurrent Malignant Melanoma


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

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.

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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective tumor response (partial or complete response) according to RECIST

Outcome Time Frame:

Up to 6 years

Safety Issue:


Principal Investigator

Elaine McWhirter

Investigator Role:

Principal Investigator

Investigator Affiliation:

Princess Margaret Hospital Phase 2 Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

January 2006

Completion Date:

Related Keywords:

  • 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
  • Lentigo
  • Melanoma
  • Hutchinson's Melanotic Freckle
  • Uveal Neoplasms