Ziv-Aflibercept in Treating and Computed Tomography Perfusion Imaging in Predicting Response in Patients With Pancreatic Neuroendocrine Tumors That Are Metastatic or Cannot Be Removed by Surgery
Study Details
Study Description
Brief Summary
This phase II trial studies ziv-aflibercept in treating and perfusion computed tomography perfusion imaging in predicting response in patients with pancreatic neuroendocrine tumors that have spread to other parts of the body or cannot be removed by surgery. Ziv-aflibercept may stop the growth of tumor cells by blocking blood flow to the tumor. Diagnostic procedures, such as computed tomography perfusion, imaging may help measure a patient's response to ziv-aflibercept treatment.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
Estimate the objective response rate (RR) of ziv-aflibercept among patients with advanced pancreatic neuroendocrine tumors (NET)s according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
-
Test the following hypotheses: that baseline perfusion computed tomography (CT) parameters can predict which patients with advanced pancreatic neuroendocrine tumors (pNETs) will respond to treatment with ziv-aflibercept.
SECONDARY OBJECTIVES:
-
Estimate progression free survival (PFS) duration among patients treated with ziv-aflibercept.
-
Evaluate the relationship between response rate and baseline blood volume (BV) and between response rate and baseline permeability surface (PS).
TERTIARY OBJECTIVES:
-
Determine whether post-treatment changes in BV expressed as relative change from baseline correlate with response to ziv-aflibercept.
-
Determine whether post-treatment tumor blood flow (BF) (absolute measurement) correlates with response to ziv-aflibercept.
-
Determine whether post-treatment changes in BF and, BV, expressed as relative change from baseline, correlate with relative change in sum of tumor diameters (RECIST 1.1 measurements).
-
Determine the effect of ziv-aflibercept therapy on post-treatment blood flow (BF), BV, mean transit time (MTT), and PS at 4 weeks after treatment.
-
Evaluate the changes in tumor perfusion parameters at time of progression.
OUTLINE:
Patients receive ziv-aflibercept intravenously (IV) over 60-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography perfusion imaging at baseline, day 21 of course 1, and at time of progression.
After completion of study treatment, patients are followed up periodically.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (ziv-aflibercept, perfusion CT) Patients receive ziv-aflibercept IV over 60-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography perfusion imaging at baseline, day 21 of course 1, and at time of progression. |
Radiation: Computed Tomography Perfusion Imaging
Undergo computed tomography perfusion imaging
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Ziv-Aflibercept
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Through study completion an average of 19 months]
90% exact confidence interval was constructed for the overall group. Per Response EvaluationCriteria In SolidTumors Criteria (RECIST v1.1) for target lesions and assessed by CT or 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
- Progression Free Survival (PFS) [Through study completion an average of 19 months]
Calculated for all eligible participants using the Kaplan Meier method and reported with confidence interval.
- Baseline Blood Volume (BV) [Baseline]
The relationship between response rate and baseline BV will be evaluated. In addition to hypothesis testing using externally generated cut-points, refinement of optimal cut points in baseline BV separating responders and non-responders will be performed. Receiver operating characteristic (ROC) curves will be generated. Response rates of perfusion computed tomography (pCT) subgroups defined by these cut-points will be compared using chi-square test. Response profiles of pCT subgroups defined by these cut-points will be compared using non-parametric test (Wilcoxon rank sum test).
- Baseline Permeability Surface (PS) [Baseline]
The relationship between response rate and baseline PS will be evaluated. In addition to hypothesis testing using externally generated cut-points, refinement of optimal cut points in baseline PS separating responders and non-responders will be performed. ROC curves will be generated. Response rates of pCT subgroups defined by these cut-points will be compared using chi-square test. Response profiles of pCT subgroups defined by these cut-points will be compared using non-parametric test (Wilcoxon rank sum test).
Other Outcome Measures
- Change in BV [Baseline to 4 weeks after treatment]
Median will be used as cut point for correlation of post-treatment changes in BV expressed as relative change from baseline with response. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate. Response profiles will be compared using non-parametric test (Wilcoxon rank sum test).
- Post-treatment Tumor Blood Flow (BF) [4 weeks after treatment]
Median will be used as cut point for correlation of post-treatment tumor BF (absolute measurement) with response. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate.
- Post-treatment Change in BF [Baseline to 4 weeks after treatment]
Continuous parameters in relative change in pCT parameters will be plotted against best relative change in sum of tumor diameters from RECIST 1.1 tumor measurements. Pearson correlation will be used to test statistical significance. Non-parametric test will be used if appropriate.
- Post-treatment Change in BV [Baseline to 4 weeks after treatment]
Continuous parameters in relative change in pCT parameters will be plotted against best relative change in sum of tumor diameters from RECIST 1.1 tumor measurements. Pearson correlation will be used to test statistical significance. Non-parametric test will be used if appropriate.
- Change in Participants Parameters [Baseline to 4 weeks after treatment]
The effect of ziv-aflibercept therapy on post-treatment BF, BV, mean transit time, and PS will be determined. Descriptive statistics of pre and post treatment values will be given. Distribution of pre and post treatment values will be graphed. Treatment induced change in values will be compared using paired-t test. Non-parametric test will be used if appropriate.
- Tumor Perfusion Parameters at Time of Progression [Up to 1 year]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have histologically or cytologically confirmed low or intermediate grade pancreatic NET; patients with neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN1) syndrome will be eligible
-
Patients must have unresectable or metastatic disease
-
Patients must have at least one measurable site of disease according to RECIST 1.1 that has not been previously irradiated
-
Patients must have at least one lesion suitable for perfusion CT; the lesion should be greater than or equal to 3 cm in size in the cranial caudal direction
-
Patient must have no contraindication for CT with iodinated contrast
-
Patients who are on a somatostatin analogue for control of hormonal syndromes must be on a stable dose (no change in mg dose of long acting octreotide or lanreotide, changes in dosing interval of +/- 1 week is allowed) for 2 months prior to date of study entry
-
Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to date of study entry; women who have had menses within the past 2 years, who have not had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy are considered to be of child-bearing potential; patients with elevated human chorionic gonadotropin (hCG) at baseline that is judged to be related to the tumor are eligible if hCG levels do not show the expected doubling when repeated 5-7 days later, or pregnancy has been ruled out by vaginal ultrasound
-
Any number of prior lines of systemic anti-neoplastic therapy are allowed; treatment with =< 1 prior VEGF inhibitor will be allowed
-
Leukocytes >= 3,000/mcL
-
Absolute neutrophil count >= 1,500/mcL
-
Platelets >= 100,000/mcL
-
Total bilirubin =< 1.5 x institutional upper limit of normal
-
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
-
Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
-
Urine protein:creatinine ratio =< 1.0 OR 24-hour urine protein =< 500 mg (24-hour total urine protein only need be obtained if urine protein:creatinine ratio < 1.0)
-
Patients must have prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) within 1.2 x the upper limit of normal
-
Patients must have resting blood pressure (BP) no greater than 140 mmHg (systolic) or 90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry
-
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
-
Less than 28 days elapsed from prior radiotherapy, from prior surgery and prior chemotherapy to the time of randomization; less than 42 days elapsed from prior major surgery to the time of randomization
-
Adverse events (with exception of alopecia, peripheral sensory neuropathy and those listed in specific exclusion criteria) from any prior anti cancer therapy of grade > 1 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] version [v.]4.0)
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 2
-
History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease
-
Other prior malignancy; adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or any other cancer from which the patient has been disease free for > 5 years are allowed
-
Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to study entry
-
Any of the following within 6 months prior to study entry: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack
-
Any of the following within 3 months prior to study entry: grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event
-
Occurrence of deep vein thrombosis within 4 weeks, prior to study entry
-
Acquired immuno deficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment
-
Any severe acute or chronic medical condition, which could impair the ability of the patient to participate to the study or to interfere with interpretation of study results
-
Pregnant or breast feeding women; positive pregnancy test (serum or urine beta-human chorionic gonadotropin [HCG]) for women of reproductive potential
-
Patient with reproductive potential (female and male) who do not agree to use an accepted effective method of contraception (hormonal or barrier methods, abstinence) during the study treatment period and for at least 3 months following completion of study treatment; for female patient enrolled, the following methods of contraception are acceptable: oral contraceptives accompanied by the use of a second method of contraception, or intra uterine device (IUD) or women who are surgically sterile, or women who are post -menopausal or other reasons have no chance of becoming pregnant
-
Absence of signed and dated Institutional Review Board-approved patient informed consent from prior to enrollment in the study
-
EXCLUSION CRITERIA RELATED TO ZIV-AFLIBERCEPT
-
Urine protein-creatinine ratio (UPCR) > 1 urinalysis or total urine protein > 500 mg/24 hours (h)
-
Serum creatinine > 1.5 x upper limit of normal (ULN); if creatinine 1.0-1.5 x ULN, creatinine clearance, calculated according to Cockcroft-Gault formula, < 60 ml/min will exclude the patient
-
History of uncontrolled hypertension, defined as systolic blood pressure > 150 mmHg while simultaneous diastolic blood pressure > 100 mmHg, or systolic blood pressure > 180 mmHg when diastolic blood pressure < 90 mmHg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment
-
Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-of- therapeutic range INR (> 3) within the 4 weeks prior to study entry
-
Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g. INR > 1.5 without vitamin K antagonist therapy), non-healing wound
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Moffitt Cancer Center-International Plaza | Tampa | Florida | United States | 33607 |
2 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
3 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Daniel Halperin, M.D. Anderson Cancer Center
Study Documents (Full-Text)
More Information
Publications
None provided.- NCI-2014-00642
- NCI-2014-00642
- 2013-0954
- 9604
- 9604
- N01CM00039
- P30CA016672
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Period Title: Overall Study | |
STARTED | 22 |
COMPLETED | 22 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Overall Participants | 22 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
17
77.3%
|
>=65 years |
5
22.7%
|
Age (years) [Mean (Full Range) ] | |
Mean (Full Range) [years] |
60.3
|
Sex: Female, Male (Count of Participants) | |
Female |
9
40.9%
|
Male |
13
59.1%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
1
4.5%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
0
0%
|
White |
21
95.5%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (participants) [Number] | |
United States |
22
100%
|
Outcome Measures
Title | Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 |
---|---|
Description | 90% exact confidence interval was constructed for the overall group. Per Response EvaluationCriteria In SolidTumors Criteria (RECIST v1.1) for target lesions and assessed by CT or 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 | Through study completion an average of 19 months |
Outcome Measure Data
Analysis Population Description |
---|
Eligible patients with baseline perfusion CT imaging. One patient from moffitt was a screen fail however 21 patients were evaluable for response and toxicity. |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 21 |
Number (90% Confidence Interval) [percentage of participants] |
9.5
43.2%
|
Title | Progression Free Survival (PFS) |
---|---|
Description | Calculated for all eligible participants using the Kaplan Meier method and reported with confidence interval. |
Time Frame | Through study completion an average of 19 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 21 |
Median (95% Confidence Interval) [months] |
10.4
|
Title | Baseline Blood Volume (BV) |
---|---|
Description | The relationship between response rate and baseline BV will be evaluated. In addition to hypothesis testing using externally generated cut-points, refinement of optimal cut points in baseline BV separating responders and non-responders will be performed. Receiver operating characteristic (ROC) curves will be generated. Response rates of perfusion computed tomography (pCT) subgroups defined by these cut-points will be compared using chi-square test. Response profiles of pCT subgroups defined by these cut-points will be compared using non-parametric test (Wilcoxon rank sum test). |
Time Frame | Baseline |
Outcome Measure Data
Analysis Population Description |
---|
Due to low response rate data were not collected |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 0 |
Title | Baseline Permeability Surface (PS) |
---|---|
Description | The relationship between response rate and baseline PS will be evaluated. In addition to hypothesis testing using externally generated cut-points, refinement of optimal cut points in baseline PS separating responders and non-responders will be performed. ROC curves will be generated. Response rates of pCT subgroups defined by these cut-points will be compared using chi-square test. Response profiles of pCT subgroups defined by these cut-points will be compared using non-parametric test (Wilcoxon rank sum test). |
Time Frame | Baseline |
Outcome Measure Data
Analysis Population Description |
---|
Due to low response rate data were not collected |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 0 |
Title | Change in BV |
---|---|
Description | Median will be used as cut point for correlation of post-treatment changes in BV expressed as relative change from baseline with response. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate. Response profiles will be compared using non-parametric test (Wilcoxon rank sum test). |
Time Frame | Baseline to 4 weeks after treatment |
Outcome Measure Data
Analysis Population Description |
---|
Due to the low response rate, data for blood volume were not collected |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 0 |
Title | Post-treatment Tumor Blood Flow (BF) |
---|---|
Description | Median will be used as cut point for correlation of post-treatment tumor BF (absolute measurement) with response. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate. Response rates will be compared using chi-square test or Fisher's exact test whenever appropriate. |
Time Frame | 4 weeks after treatment |
Outcome Measure Data
Analysis Population Description |
---|
Response rate was too low to power a valid analysis. |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 0 |
Title | Post-treatment Change in BF |
---|---|
Description | Continuous parameters in relative change in pCT parameters will be plotted against best relative change in sum of tumor diameters from RECIST 1.1 tumor measurements. Pearson correlation will be used to test statistical significance. Non-parametric test will be used if appropriate. |
Time Frame | Baseline to 4 weeks after treatment |
Outcome Measure Data
Analysis Population Description |
---|
Response rate was too low to power a valid analysis. |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 0 |
Title | Post-treatment Change in BV |
---|---|
Description | Continuous parameters in relative change in pCT parameters will be plotted against best relative change in sum of tumor diameters from RECIST 1.1 tumor measurements. Pearson correlation will be used to test statistical significance. Non-parametric test will be used if appropriate. |
Time Frame | Baseline to 4 weeks after treatment |
Outcome Measure Data
Analysis Population Description |
---|
Response rate was too low to power a valid analysis. |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 0 |
Title | Change in Participants Parameters |
---|---|
Description | The effect of ziv-aflibercept therapy on post-treatment BF, BV, mean transit time, and PS will be determined. Descriptive statistics of pre and post treatment values will be given. Distribution of pre and post treatment values will be graphed. Treatment induced change in values will be compared using paired-t test. Non-parametric test will be used if appropriate. |
Time Frame | Baseline to 4 weeks after treatment |
Outcome Measure Data
Analysis Population Description |
---|
Response rate was too low to power a valid analysis. |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 0 |
Title | Tumor Perfusion Parameters at Time of Progression |
---|---|
Description | |
Time Frame | Up to 1 year |
Outcome Measure Data
Analysis Population Description |
---|
No patients underwent perfusion CT at time of progression, no analysis could not be performed. |
Arm/Group Title | Aflibercept 6 mg /kg IV |
---|---|
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. |
Measure Participants | 0 |
Adverse Events
Time Frame | C1D1 and for 30 days after the last dose of study drug. | |
---|---|---|
Adverse Event Reporting Description | Patients will be followed until resolution or stabilization of the adverse event. | |
Arm/Group Title | Aflibercept 6 mg /kg IV | |
Arm/Group Description | Aflibercept 6 mg /kg IV every 3 weeks. | |
All Cause Mortality |
||
Aflibercept 6 mg /kg IV | ||
Affected / at Risk (%) | # Events | |
Total | 1/22 (4.5%) | |
Serious Adverse Events |
||
Aflibercept 6 mg /kg IV | ||
Affected / at Risk (%) | # Events | |
Total | 4/22 (18.2%) | |
Blood and lymphatic system disorders | ||
Hemorrhage Upper GI | 1/22 (4.5%) | |
Gastrointestinal disorders | ||
Pain Abdominal | 1/22 (4.5%) | |
cholecystitis | 1/22 (4.5%) | |
Metabolism and nutrition disorders | ||
Dehydration | 1/22 (4.5%) | |
Other (Not Including Serious) Adverse Events |
||
Aflibercept 6 mg /kg IV | ||
Affected / at Risk (%) | # Events | |
Total | 21/22 (95.5%) | |
Blood and lymphatic system disorders | ||
Anemia | 3/22 (13.6%) | |
Platelet count decreased | 3/22 (13.6%) | |
Gastrointestinal disorders | ||
Abdominal pain | 5/22 (22.7%) | |
Constipation | 5/22 (22.7%) | |
Diarrhea | 4/22 (18.2%) | |
Mucositis oral | 10/22 (45.5%) | |
Nausea | 5/22 (22.7%) | |
Upper gastrointestinal hemorrhage | 1/22 (4.5%) | |
Vomiting | 5/22 (22.7%) | |
General disorders | ||
Fatigue | 6/22 (27.3%) | |
Pain | 3/22 (13.6%) | |
Investigations | ||
Alanine aminotransferase increased | 4/22 (18.2%) | |
Aspartate aminotransferase increased | 3/22 (13.6%) | |
Creatinine increased | 3/22 (13.6%) | |
Neutrophil count decreased | 3/22 (13.6%) | |
Metabolism and nutrition disorders | ||
Anorexia | 3/22 (13.6%) | |
Weight loss | 3/22 (13.6%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 4/22 (18.2%) | |
Nervous system disorders | ||
Headache | 15/22 (68.2%) | |
Renal and urinary disorders | ||
Proteinuria | 7/22 (31.8%) | |
Respiratory, thoracic and mediastinal disorders | ||
Epistaxis | 3/22 (13.6%) | |
Hoarseness | 9/22 (40.9%) | |
Sinusitis | 2/22 (9.1%) | |
Skin and subcutaneous tissue disorders | ||
Palmar-plantar erythrodysesthesia syndrome | 3/22 (13.6%) | |
Vascular disorders | ||
Hypertension | 17/22 (77.3%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Dr. Daniel M. Halperin/ GI Medical Oncology |
---|---|
Organization | UT MD Anderson Cancer Center |
Phone | 713-792-2828 |
DMHalperin@mdanderson.org |
- NCI-2014-00642
- NCI-2014-00642
- 2013-0954
- 9604
- 9604
- N01CM00039
- P30CA016672