A Phase 2 interventional study of cediranib maleate and laboratory biomarker analysis in Advanced Malignant Mesothelioma, Epithelial Mesothelioma and Recurrent Malignant Mesothelioma, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-01-23.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
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
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.
470 studies on the registry are indexed under Mesothelioma; 75 are open to participants now.
This study's enrollment of 54 is above the median of 40 across 371 interventional studies indexed under Mesothelioma.
Browse Mesothelioma studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
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Inclusion Criteria:
Histologically confirmed epithelial, sarcomatous, or biphasic malignant pleural mesothelioma
Unresectable disease
Performance status
Must have New York Heart Association class I or II disease
Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate · Other: laboratory biomarker analysis
Given orally
Also known as: AZD2171, Recentin
Correlative studies
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.
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.
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.
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.
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.
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
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.
| Milestone | AZD2171 (Cediranib Maleate) |
|---|---|
| Started | 54 |
| Completed | 0 |
| Not completed | 54 |
| Withdrew: Ineligible | 6 |
| Withdrew: Adverse event | 6 |
| Withdrew: Withdrawal by subject | 2 |
| Withdrew: Lack of efficacy | 36 |
| Withdrew: Death | 2 |
| Withdrew: Not protocol specified | 1 |
| Withdrew: Did not receive any treatment | 1 |
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.".
| percentage of participants | AZD2171 (Cediranib Maleate) |
|---|---|
| Overall Response Rate | 9 (2 to 20) |
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.
| months | AZD2171 |
|---|---|
| Overall Survival | 9.5 (5.6 to 10.7) |
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
| months | AZD2171 |
|---|---|
| Progression-free Survival | 2.6 (1.7 to 3.7) |
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.
| percentage of participants | AZD2171 |
|---|---|
| Disease Control Rate | 44 (28 to 58) |
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.
| percentage of participants | AZD2171 |
|---|---|
| Objective Response Rate Per Modified RECIST for Pleural Tumors | 2 (0 to 11) |
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.
| Participants | AZD2171 (Cediranib Maleate) |
|---|---|
| Adverse Event Rates | 47 |
Only adverse events that are possibly, probably or definitely related to study drug are reported.
| Participants | AZD2171 (Cediranib Maleate) |
|---|---|
| Anorexia | 3 |
| Apnea | 1 |
| Ataxia (incoordination) | 1 |
| Cognitive disturbance | 1 |
| Colitis | 1 |
| Confusion | 2 |
| Constipation | 1 |
| Dehydration | 3 |
| Diarrhea | 4 |
| Dizziness | 1 |
| Encephalopathy | 1 |
| Fatigue (asthenia, lethargy, malaise) | 7 |
| Hypertension | 15 |
| Hypotension | 1 |
| Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 1 |
| Memory impairment | 1 |
| Metabolic/Laboratory-Other (Specify) | 1 |
| Muscle weakness, not d/t neuropathy - body/general | 1 |
| Nausea | 2 |
| Necrosis, GI - Esophagus | 1 |
| Neuropathy: sensory | 1 |
| Pain - Chest wall | 1 |
| Pain - Head/headache | 1 |
| Pain - Intestine | 1 |
| Pain - Pain NOS | 1 |
| Pain - Tumor pain | 1 |
| Perforation, GI - Ileum | 1 |
| Potassium, serum-low (hypokalemia) | 1 |
| Proteinuria | 2 |
| Rash: hand-foot skin reaction | 2 |
| Renal failure | 2 |
| Sodium, serum-low (hyponatremia) | 1 |
| Speech impairment (e.g., dysphasia or aphasia) | 1 |
| Thrombosis/thrombus/embolism | 3 |
| Vomiting | 1 |
| Weight loss | 2 |
Collected over Daily during protocol treatment.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AZD2171 | — | 22/47 (46.8%) | 42/47 (89.4%) |
| Event | AZD2171 |
|---|---|
| Death - Disease progression NOSNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 8/47 |
| Inf w/normal ANC or Gr 1-2 neutrophils - LungInfections and infestations | 3/47 |
| DehydrationMetabolism and nutrition disorders | 3/47 |
| ConfusionPsychiatric disorders | 2/47 |
| Renal failureRenal and urinary disorders | 2/47 |
| Thrombosis/thrombus/embolismVascular disorders | 2/47 |
| Thyroid function, low (hypothyroidism)Endocrine disorders | 1/47 |
| ConstipationGastrointestinal disorders | 1/47 |
| Gastrointestinal-Other (Specify)Gastrointestinal disorders | 1/47 |
| Necrosis, GI - EsophagusGastrointestinal disorders | 1/47 |
| Event | AZD2171 |
|---|---|
| Fatigue (asthenia, lethargy, malaise)General disorders | 35/47 |
| HypertensionVascular disorders | 34/47 |
| DiarrheaGastrointestinal disorders | 30/47 |
| AnorexiaMetabolism and nutrition disorders | 20/47 |
| Glucose, serum-high (hyperglycemia)Metabolism and nutrition disorders | 18/47 |
| Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders | 18/47 |
| NauseaGastrointestinal disorders | 17/47 |
| Weight lossInvestigations | 17/47 |
| Voice changes/dysarthriaRespiratory, thoracic and mediastinal disorders | 17/47 |
| ProteinuriaRenal and urinary disorders | 14/47 |
Only eligible patients who received protocol treatment are included in the analysis. Of the 54 patients enrolled, 6 were ineligible and 1 addtional patients refused protocol treatment.
| Age, Continuous(years) | AZD2171 |
|---|---|
| Median | 66 (43 to 84) |
| Sex: Female, Male(Participants) | AZD2171 |
|---|---|
| Female | 9 |
| Male | 38 |
| Ethnicity (NIH/OMB)(Participants) | AZD2171 |
|---|---|
| Hispanic or Latino | 2 |
| Not Hispanic or Latino | 41 |
| Unknown or Not Reported | 4 |
| Race (NIH/OMB)(Participants) | AZD2171 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 44 |
| More than one race | 0 |
| Unknown or Not Reported | 3 |
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