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

• ClinicalTrials.gov Identifier: NCT00243074
• Recruitment Status: Completed
• First Posted: October 21, 2005
• Results First Posted: October 21, 2015
• Last Update Posted: January 23, 2018
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: October 20, 2005
• First Posted Date: October 21, 2005
• Results First Submitted Date: October 30, 2012
• Results First Posted Date: October 21, 2015
• Last Update Posted Date: January 23, 2018
• Study Start Date: November 2005
• Actual Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2015)

Overall Response Rate [ Time Frame: 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.".

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: December 27, 2017)

• Overall Survival [ Time Frame: 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.
• Progression-free Survival [ Time Frame: 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 [ Time Frame: 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.
• Objective Response Rate Per Modified RECIST for Pleural Tumors [ Time Frame: 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.
• Adverse Event Rates [ Time Frame: 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 [ Time Frame: 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: S0509 - AZD2171 in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed By Surgery
• Official Title: A Phase II Trial of Novel Oral Anti-Angiogenic Agent AZD2171 (NSC-732208) in Malignant Pleural Mesothelioma
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Malignant Mesothelioma
• Epithelial Mesothelioma
• Recurrent Malignant Mesothelioma
• Sarcomatous Mesothelioma

Intervention

• Drug: cediranib maleate
  Given orally
  Other Names:

  • AZD2171
  • Recentin
• Other: laboratory biomarker analysis
  Correlative studies

Study Arms

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.

Interventions:

• Drug: cediranib maleate
• Other: laboratory biomarker analysis

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 21, 2015): 54
• Original Enrollment: Not Provided
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00243074
• Other Study ID Numbers: NCI-2012-02902; S0509; U10CA032102 ( U.S. NIH Grant/Contract ); CDR0000446178 ( Registry Identifier: PDQ (Physician Data Query) )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Cancer Institute (NCI)
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: SWOG Cancer Research Network
• Collaborators: Not Provided

Investigators

• Principal Investigator: Linda Garland; SWOG Cancer Research Network

• PRS Account: National Cancer Institute (NCI)
• Verification Date: February 2014