Advanced Malignant Mesothelioma, Epithelial Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatous Mesothelioma
Conditions
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.
Interventions
DRUGcediranib maleate
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZD2171 | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Death | 2 |
| Overall Study | Did not receive any treatment | 1 |
| Overall Study | Ineligible | 6 |
| Overall Study | Lack of Efficacy | 36 |
| Overall Study | not protocol specified | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | AZD2171 |
|---|---|
| Age, Continuous | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 47 |
| serious Total, serious adverse events | 22 / 47 |
Outcome results
Primary
Overall Response Rate
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..
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.
Population: Eligible patients who received any amount of AZD2171
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 (Cediranib Maleate) | Overall Response Rate | 9 percentage of participants |
Secondary
Adverse Event Rates
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.
Time frame: Daily during protocol treatment
Population: All patients who received protocol treatment were assessed for adverse events. See adverse event tables for specific details.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD2171 (Cediranib Maleate) | Adverse Event Rates | 47 Participants |
Secondary
Adverse Events
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Patients were assessed for adverse events every day for as long as they remained on protocol treatment, up to 5 years.
Population: Eligible patients who received any amount of protocol treatment with AZD2171 (cediranib maleate)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD2171 (Cediranib Maleate) | Adverse Events | Memory impairment | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Potassium, serum-low (hypokalemia) | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Proteinuria | 2 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Rash: hand-foot skin reaction | 2 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Renal failure | 2 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Sodium, serum-low (hyponatremia) | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Speech impairment (e.g., dysphasia or aphasia) | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Thrombosis/thrombus/embolism | 3 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Vomiting | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Weight loss | 2 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Perforation, GI - Ileum | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Anorexia | 3 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Apnea | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Ataxia (incoordination) | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Cognitive disturbance | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Colitis | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Confusion | 2 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Constipation | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Dehydration | 3 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Diarrhea | 4 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Dizziness | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Encephalopathy | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Fatigue (asthenia, lethargy, malaise) | 7 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Hypertension | 15 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Hypotension | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Metabolic/Laboratory-Other (Specify) | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Muscle weakness, not d/t neuropathy - body/general | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Nausea | 2 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Necrosis, GI - Esophagus | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Neuropathy: sensory | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Pain - Chest wall | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Pain - Head/headache | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Pain - Intestine | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Pain - Pain NOS | 1 Participants |
| AZD2171 (Cediranib Maleate) | Adverse Events | Pain - Tumor pain | 1 Participants |
Secondary
Disease Control Rate
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.
Time frame: Every 8 weeks until disease progression progression, up to 5 years.
Population: Eligible patients who received AZD2171
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 (Cediranib Maleate) | Disease Control Rate | 44 percentage of participants |
Secondary
Objective Response Rate Per Modified RECIST for Pleural Tumors
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.
Time frame: Disease assessments for response were performed every 8 weeks as long as the patient remained on protocol treatment, up to 5 years.
Population: Eligible patients who received any amount of AZD2171
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 (Cediranib Maleate) | Objective Response Rate Per Modified RECIST for Pleural Tumors | 2 percentage of participants |
Secondary
Overall Survival
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.
Time frame: Daily during protocol treatment; then every 8 weeks until progression; then every 6 months for up to 3 years.
Population: Eligible patients who received AZD2171
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD2171 (Cediranib Maleate) | Overall Survival | 9.5 months |
Secondary
Progression-free Survival
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
Time frame: Every 8 weeks until disease progression or death, up to 5 years.
Population: Eligible patients who received AZD2171
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD2171 (Cediranib Maleate) | Progression-free Survival | 2.6 months |