S0509 - AZD2171 in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed By Surgery

Phase 2

Completed

Conditions: Advanced Malignant Mesothelioma
Recurrent Malignant Mesothelioma
Sarcomatous Mesothelioma
Epithelial Mesothelioma

Interventions: Drug: cediranib maleate
Other: laboratory biomarker analysis

Registration Number: NCT00243074

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is study how well AZD2171 works in treating patients with malignant pleural mesothelioma that cannot be removed by surgery. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor

Detailed Description: PRIMARY OBJECTIVES:

I. Determine the objective confirmed, complete, and partial response rates in patients with unresectable malignant pleural mesothelioma treated with AZD2171.

SECONDARY OBJECTIVES:

I. Determine the clinical benefit, in terms of objective response and stable disease rates, in patients treated with this drug.

II. Determine the 1-year median overall survival and progression-free survival in patients treated with this drug.

III. Determine the frequency and severity of toxic effects in patients treated with this drug.

IV. Correlate, preliminarily, pre- and post-treatment plasma vascular endothelial growth factor and soluble vascular cell adhesion molecule with clinical outcomes in patients treated with this drug.

V. Correlate, preliminarily, circulating endothelial cells with clinical outcomes in patients treated with this drug.

VI. Correlate variants of genes in the pathway targeted by this drug and variants of genes involved in the development of hypertension with the antiangiogenic property of this drug in these patients.

OUTLINE:

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 periodically for up to 5 years from study entry.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

Inclusion Criteria

Histologically confirmed epithelial, sarcomatous, or biphasic malignant pleural mesothelioma
- Unresectable disease
  - Residual disease after prior cytoreductive surgery allowed
Measurable disease by CT scan or MRI
Prior treatment with platinum-based chemotherapy required
No known CNS metastasis
Performance status
- Zubrod 0-2
WBC >= 3,000/mm^3
Absolute neutrophil count >= 1,500/mm^3
Platelet count >= 100,000/mm^3
AST or ALT =< 1.5 times upper limit of normal (ULN)
Bilirubin normal
Creatinine =< 1.5 times ULN OR
Creatinine clearance >= 50 mL/min
Proteinuria =< 1+ by 2 consecutive dipstick tests taken >= 1 week apart
No history of familial long QT syndrome
Mean QTc =< 470 msec
Systolic BP =< 150 mm Hg AND diastolic BP =< 100 mm Hg
Must have New York Heart Association class I or II disease
- Class II must be controlled with treatment
Able to swallow and/or receive enteral medications via gastrostomy feeding tube
Not requiring IV alimentation
No active peptic ulcer
No intractable nausea or vomiting
Not pregnant or nursing
Fertile patients must use effective contraception
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in remission
No history of hypersensitivity reaction to compounds of similar chemical or biological composition to the study drug
Prior monoclonal antibody therapy targeting vascular endothelial growth factor (VEGF), VEGF receptor 1(VEGFR1) or VEGF receptor 2 (VEGFR2) allowed
No other prior immunotherapy or biologic therapy
No prior thymidine kinase inhibitor against VEGFR1 or VEGFR2
No concurrent drugs or biologics with proarrhythmic potential
No more than 1 prior chemotherapy regimen
At least 28 days since prior chemotherapy (42 days for nitrosoureas or mitomycin) and recovered
At least 21 days since prior radiotherapy and recovered
At least 28 days since prior major surgery (e.g., thoracotomy or laparotomy) and recovered
No prior surgery that would affect absorption
Stable antihypertensive therapy allowed provided blood pressure (BP) parameters are met
Concurrent enrollment on SWOG-S9925 allowed
No concurrent combination antiretroviral therapy for HIV-positive patients

Exclusion Criteria

Not provided

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (cediranib maleate)	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.
Treatment (cediranib maleate)	laboratory biomarker analysis	Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	Disease assessments for response were performed every 8 weeks for as long as the patient remained on protocol treatment, up to 5 years.	confirmed complete and partial responses per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.".

Secondary Outcome Measures

Name	Time	Method
Adverse Event Rates	Daily during protocol treatment	Adverse events per the NCI Common Toxicity Criteria version 3.0 that were possibly, probably or definitely related to protocol treatment. See adverse event tables for specific details.
Adverse Events	Patients were assessed for adverse events every day for as long as they remained on protocol treatment, up to 5 years.	Only adverse events that are possibly, probably or definitely related to study drug are reported.
Progression-free Survival	Every 8 weeks until disease progression or death, up to 5 years.	From the date of enrollment until the date of disease progression (as determined by standard RECIST), symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at the date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Disease Control Rate	Every 8 weeks until disease progression progression, up to 5 years.	The percentage of patients with a best of response of stable disease or better per standard RECIST. That is, patients whose best response was not increasing disease or death.
Overall Survival	Daily during protocol treatment; then every 8 weeks until progression; then every 6 months for up to 3 years.	From the date of enrollment until the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.
Objective Response Rate Per Modified RECIST for Pleural Tumors	Disease assessments for response were performed every 8 weeks as long as the patient remained on protocol treatment, up to 5 years.	The sum of 6 pleural thickness measurements is added to sum of the longest diameters of all non-pleural measurable lesions. The resulting values are evaluated using RECIST.

Trial Locations

Locations (1): Southwest Oncology Group
🇺🇸
San Antonio, Texas, United States

S0509 - AZD2171 in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed By Surgery

Recruitment & Eligibility

Study & Design

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