Advanced Malignant MesotheliomaPhase 2NCT00309946
Cediranib Maleate in Treating Patients With Malignant Mesothelioma That Cannot Be Removed By Surgery
A Phase 2 study testing cediranib maleate in people with Advanced Malignant Mesothelioma and Epithelial Mesothelioma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well cediranib maleate works in treating patients with malignant mesothelioma that cannot be removed by surgery. Cediranib maleate 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Localized Malignant Mesothelioma
- What is being tested?
- cediranib maleate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2005to Sep 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed malignant pleural, peritoneal, or tunica vaginalis mesothelioma
- Epithelial, sarcomatoid, or mixed subtype
- International Mesothelioma Interest Group stage II-IV disease (for patients with pleural mesothelioma)
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR > 10 mm by spiral CT scan
- Pleural effusion and ascites are not considered measurable lesions
- Disease not amenable to curative surgery
Show all 47Show fewer
- No known brain metastases
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS 70-100%
- Life expectancy > 3 months
- White blood cell (WBC) ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Hemoglobin ≥ 8 g/dL
- Platelets ≥ 100,000/mm³
- Total bilirubin normal
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal(ULN)
- Creatinine normal OR creatinine clearance > 60 mL/min
- Fertile patients must use effective contraception
- Not pregnant or nursing
- Negative pregnancy test
- No history of allergic reactions to compounds of similar chemical or biologic composition to AZD2171
- Mean corrected QT interval (QTc) ≤ 500 msec (with Bazett's correction) by EKG
- No history of long QT syndrome
- Proteinuria ≤ 1+ on two consecutive dipsticks taken ≥ 1 week apart
- No other concurrent malignancy
- No New York Heart Association class III or IV cardiac disease
- No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Hypertension
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit study compliance
- No more than 1 prior cytotoxic chemotherapy
- Prior intrapleural cytotoxic agents (including bleomycin) do not count towards prior cytotoxic chemotherapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- No prior radiotherapy to the only site of measurable disease
- At least 4 weeks since prior radiotherapy and recovered
- At least 4 weeks since prior major surgery and recovered
- More than 30 days since prior participation in an investigational trial
- No prior treatment with a vascular endothelial growth factor (VEGF) inhibitor
- No other concurrent investigational agents
- No concurrent commercial agents for the malignancy
- No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, or pentamidine)
- No concurrent hematopoietic growth factors except epoetin alfa
- No concurrent palliative radiotherapy
- No combination antiretroviral therapy for HIV-positive patients
- No concurrent drugs or biologics with proarrhythmic potential
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470
About this study
Official title: Phase II Study of AZD2171 (NSC#732208) in Patients With Malignant Mesothelioma
This phase II trial is studying how well cediranib maleate works in treating patients with malignant mesothelioma that cannot be removed by surgery. Cediranib maleate 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
Read the detailed description
We conducted a multi-center phase II trial of cediranib in patients with unresectable, histologically-confirmed malignant mesothelioma (MM) who had received <=1 prior regimen of chemotherapy. The primary endpoint was objective response rate. Initial cediranib dosing was 45 mg daily during a 28-day cycle. Due to substantial toxicity, the starting dose was subsequently lowered to 30 mg daily.
Pretreatment evaluation included a medical history and physical exam, complete blood count and differential, chemistry panel, pregnancy test, and a computed tomography (CT) scan of the chest, abdomen, and pelvis if relevant. A history and physical exam were repeated every 14 days and laboratory evaluations including a complete blood count with differential, serum chemistry panel, and urinalysis were repeated every 7 days. Patients were provided with a blood pressure monitoring device and a diary to record their blood pressure readings twice daily.
Patients received a minimum of 2 cycles unless unacceptable toxicity or rapid clinical progression of disease occurred. Response was evaluated by CT imaging every two cycles. Confirmatory scans were to be obtained at least 4 weeks after initial documentation of an objective complete or partial response.
Cediranib was administered orally once daily on days 1 through 28 of a 28-day cycle. Cediranib was initially dosed at 45 mg daily, but due to substantial rates of toxicity the protocol was amended in June 2007 to decrease the starting dose to 30 mg daily. Cediranib was taken 1 hour (h) before or 2 h after meals. Only one dose modification was permitted. When the starting cediranib dose was 45 mg, dose level-1 was 30 mg daily. After the protocol amendment, dose level-1 was 20 mg daily. Further dose reductions were allowed at the discretion of the investigator only if the patient had received clinical benefit from cediranib for >3 months. Patients undergo blood collection periodically during study for biomarker and optional pharmacogenomic correlative studies. After completion of study treatment, patients are followed for up to 8 weeks.
Adverse effects were graded according to National Cancer Institute Common Toxicity Criteria version 3.0. The dose was reduced for grade 3 or greater non-hematologic toxicity attributable to cediranib or grade 4 hematologic toxicity if the toxicity lasted for >5 days and did not resolve to <=grade 2. Maximal antihypertensive therapy was defined as taking 4 antihypertensive agents for >2 weeks at full dosage. For patients on antihypertensive therapy who had an elevation in systolic blood pressure (SBP) >=140 mmHg or diastolic blood pressure (DBP) >=90 mmHg on 2 separate readings during a 48 h period, the dose of cediranib was maintained without interruption while the dosage of current antihypertensive therapy was increased or an additional antihypertensive agent was started. If 2 readings reported a SBP >=180 mmHg or a DBP >=105 mmHg during a 1 week period, cediranib was held and there was either an increase in the dosage of current antihypertensive therapy or an additional antihypertensive agent was added. Resumption of cediranib was allowed only after the blood pressure was <140/90 mmHg. If 2 blood pressure readings recorded an SBP >=160 mmHg or a DBP >=105 mmHg 1 h apart during a 48 hour period in a patient already on maximal antihypertensive therapy, cediranib was held and treatment was resumed at 1 dose level lower when the blood pressure was <160/105.
PRIMARY OBJECTIVE:
- Determine the objective response rate in patients with malignant pleural, peritoneal, or tunica vaginalis mesothelioma that is not amenable to curative surgery who are treated with AZD2171 (cediranib maleate).
SECONDARY OBJECTIVES:
- Determine the progression-free survival of patients treated with AZD2171. II. Determine the toxicity experienced by patients treated with AZD2171. III. Determine median and overall survival of patients treated with AZD2171.
TERTIARY OBJECTIVES:
- Generate preliminary data regarding potential utility of pharmacogenomic and plasma/serum biomarkers of angiogenesis as predictive or prognostic markers for future investigations of this drug in malignant mesothelioma.
- Conditions
- Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Localized Malignant Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatous Mesothelioma
- Being tested
- cediranib maleate
- Medical subject headings
- Mesothelioma, Malignant, Solitary Fibrous Tumor, Pleural
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cediranib maleateDrug
Also called AZD2171, Recentin
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Initial cediranib maleate dosing was 45 mg (once daily) during a 28-day cycle. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. Due to substantial toxicity, the starting dose was subsequently lowered to 30 mg daily. Receives: Drug: cediranib maleate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate, Complete (CR) or Partial (PR) Response
Evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met.
Measured: Every 8 weeks
Secondary outcomes (2)
Changes in Laboratory Correlates
Examined using paired t-test or Wilcoxon signed-ranks test.
Measured: Baseline, days 15 and 29 of course 1, and then every 28 days
Pharmacogenomics by Correlating Genetic Polymorphisms With Drug Activity and Toxicity
Focus on variants of genes in the pathway targeted by cediranib maleate, including kdr/flk-1 (the specific target of cediranib maleate) and the genes that encode Vascular endothelial growth factor A (VEGF-A) or HIF1α. If additional information relevant to other genes of interest in the pathway becomes available the samples will be utilized for such analysis as well.
Measured: Week 1 of course 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2006 (estimated)
- Study startDec 2005
- Primary completionSep 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Malignant MesotheliomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Hedy Kindler, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00309946
- Sponsor's protocol ID
- NCI-2009-00126
- Other IDs
- N01CM17102, CDR0000463521, 14203B
- Status last verified
- Oct 2013
- First submitted
- 29 Mar 2006
- Last updated
- 31 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Campbell NP, Kunnavakkam R, Leighl N, Vincent MD, Gandara DR, Koczywas M, Gitlitz BJ, Agamah E, Thomas SP, Stadler WM, Vokes EE, Kindler HL. Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium. Lung Cancer. 2012 Oct;78(1):76-80. doi: 10.1016/j.lungcan.2012.06.011. Epub 2012 Jul 23.
PubMed 22831987
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of AZD2171 (NSC#732208) in Patients With Malignant Mesothelioma
- ClinicalTrials.gov ID
- NCT00309946
- Acronym / sponsor ID
- NCI-2009-00126
- Conditions
- Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Localized Malignant Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatous Mesothelioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2005
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 3 Apr 2006 (estimated)
- Results
- Posted 10 Sep 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well cediranib maleate works in treating patients with malignant mesothelioma that cannot be removed by surgery. Cediranib maleate 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
We conducted a multi-center phase II trial of cediranib in patients with unresectable, histologically-confirmed malignant mesothelioma (MM) who had received <=1 prior regimen of chemotherapy. The primary endpoint was objective response rate. Initial cediranib dosing was 45 mg daily during a 28-day cycle. Due to substantial toxicity, the starting dose was subsequently lowered to 30 mg daily.
Pretreatment evaluation included a medical history and physical exam, complete blood count and differential, chemistry panel, pregnancy test, and a computed tomography (CT) scan of the chest, abdomen, and pelvis if relevant. A history and physical exam were repeated every 14 days and laboratory evaluations including a complete blood count with differential, serum chemistry panel, and urinalysis were repeated every 7 days. Patients were provided with a blood pressure monitoring device and a diary to record their blood pressure readings twice daily.
Patients received a minimum of 2 cycles unless unacceptable toxicity or rapid clinical progression of disease occurred. Response was evaluated by CT imaging every two cycles. Confirmatory scans were to be obtained at least 4 weeks after initial documentation of an objective complete or partial response.
Cediranib was administered orally once daily on days 1 through 28 of a 28-day cycle. Cediranib was initially dosed at 45 mg daily, but due to substantial rates of toxicity the protocol was amended in June 2007 to decrease the starting dose to 30 mg daily. Cediranib was taken 1 hour (h) before or 2 h after meals. Only one dose modification was permitted. When the starting cediranib dose was 45 mg, dose level-1 was 30 mg daily. After the protocol amendment, dose level-1 was 20 mg daily. Further dose reductions were allowed at the discretion of the investigator only if the patient had received clinical benefit from cediranib for >3 months. Patients undergo blood collection periodically during study for biomarker and optional pharmacogenomic correlative studies. After completion of study treatment, patients are followed for up to 8 weeks.
Adverse effects were graded according to National Cancer Institute Common Toxicity Criteria version 3.0. The dose was reduced for grade 3 or greater non-hematologic toxicity attributable to cediranib or grade 4 hematologic toxicity if the toxicity lasted for >5 days and did not resolve to <=grade 2. Maximal antihypertensive therapy was defined as taking 4 antihypertensive agents for >2 weeks at full dosage. For patients on antihypertensive therapy who had an elevation in systolic blood pressure (SBP) >=140 mmHg or diastolic blood pressure (DBP) >=90 mmHg on 2 separate readings during a 48 h period, the dose of cediranib was maintained without interruption while the dosage of current antihypertensive therapy was increased or an additional antihypertensive agent was started. If 2 readings reported a SBP >=180 mmHg or a DBP >=105 mmHg during a 1 week period, cediranib was held and there was either an increase in the dosage of current antihypertensive therapy or an additional antihypertensive agent was added. Resumption of cediranib was allowed only after the blood pressure was <140/90 mmHg. If 2 blood pressure readings recorded an SBP >=160 mmHg or a DBP >=105 mmHg 1 h apart during a 48 hour period in a patient already on maximal antihypertensive therapy, cediranib was held and treatment was resumed at 1 dose level lower when the blood pressure was <160/105.
PRIMARY OBJECTIVE:
- Determine the objective response rate in patients with malignant pleural, peritoneal, or tunica vaginalis mesothelioma that is not amenable to curative surgery who are treated with AZD2171 (cediranib maleate).
SECONDARY OBJECTIVES:
- Determine the progression-free survival of patients treated with AZD2171. II. Determine the toxicity experienced by patients treated with AZD2171. III. Determine median and overall survival of patients treated with AZD2171.
TERTIARY OBJECTIVES:
- Generate preliminary data regarding potential utility of pharmacogenomic and plasma/serum biomarkers of angiogenesis as predictive or prognostic markers for future investigations of this drug in malignant mesothelioma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzyme inhibitor therapy) | Experimental | Drug: cediranib maleateInitial cediranib maleate dosing was 45 mg (once daily) during a 28-day cycle. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. Due to substantial toxicity, the starting dose was subsequently lowered to 30 mg daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (47 listed)
- Histologically or cytologically confirmed malignant pleural, peritoneal, or tunica vaginalis mesothelioma
- International Mesothelioma Interest Group stage II-IV disease (for patients with pleural mesothelioma)
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR > 10 mm by spiral CT scan
- Disease not amenable to curative surgery
- No known brain metastases
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cediranib maleateAlso: AZD2171, RecentinGiven orally | Drug | Treatment (enzyme inhibitor therapy) |
Primary outcome
Objective Response Rate, Complete (CR) or Partial (PR) Response
Time frame: Every 8 weeks
Evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met.
2 secondary outcomes
Changes in Laboratory Correlates
Time frame: Baseline, days 15 and 29 of course 1, and then every 28 days
Pharmacogenomics by Correlating Genetic Polymorphisms With Drug Activity and Toxicity
Time frame: Week 1 of course 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22831987Campbell NP, Kunnavakkam R, Leighl N, Vincent MD, Gandara DR, Koczywas M, Gitlitz BJ, Agamah E, Thomas SP, Stadler WM, Vokes EE, Kindler HL. Cediranib in patients with malignant mesothelioma: a phase II trial of the University of Chicago Phase II Consortium. Lung Cancer. 2012 Oct;78(1):76-80. doi: 10.1016/j.lungcan.2012.06.011. Epub 2012 Jul 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hedy Kindler principal investigator
University of Chicago Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cediranib maleate in people with Advanced Malignant Mesothelioma and Epithelial Mesothelioma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 47 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate, Complete (CR) or Partial (PR) Response (time frame: Every 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00309946, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2014.