Clinical trial NCT00243061: AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma
Official title: A Phase II Study of AZD2171 in Previously Untreated Patients With Metastatic or Recurrent Malignant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-10-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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: 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 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

Primary outcomes:
measure: Objective Tumor Response (Partial or Complete Response) According to RECIST
timeFrame: Up to 6 years
measure: Prolonged Stable Disease According to RECIST
timeFrame: Up to 6 months
Secondary outcomes:
measure: Median Survival Time
timeFrame: Up to 6 years
measure: Survival Rate
timeFrame: At 1 year
measure: Response Duration
timeFrame: 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
measure: Stable Disease Duration
timeFrame: From the start of the treatment until the criteria for progression are met, assessed up to 6 years
measure: Highest Toxicity Grade Assessed by NCI CTCAE Version 3.0
timeFrame: Up to 6 years after completion of treatment
measure: Time to Disease Progression
timeFrame: Up to 6 years
measure: Clinical Benefit Response
timeFrame: Up to 6 years
measure: Changes in Levels of Soluble Angiogenic Factors
timeFrame: From baseline to up to 6 years
measure: Change in Vessel Permeability and Blood Flow by DCE-MRI
timeFrame: From baseline to up to 28 days after starting daily oral dosing
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Hospital Phase 2 Consortium
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital Phase 2 Consortium
name: Elaine McWhirter
role: PRINCIPAL_INVESTIGATOR
References: