AZD2171 to Treat Prostate Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00436956
• Collaborator: (none)
• Enrollment: 59
• Location: 1
• Arm: 1
• Actual Duration (Months): 87.7
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Background:

• AZD2171 (Cediranib) is an experimental drug that inhibits formation of new blood vessels.

• Tumors need new blood vessels to grow. Preventing the growth of new blood vessels with AZD2171 may inhibit tumor growth.

Objectives:

-To determine the effectiveness and side effects of AZD2171 in patients with prostate cancer that has metastasized (spread beyond the primary site).

Eligibility:

• Males 18 years of age and older with androgen-independent prostate cancer that has metastasized.

• Patients must have received prior treatment with docetaxel.

Design:

Patients take one AZD2171 by mouth every day in 28-day treatment cycles and undergo the following procedures:

• 1- to 2-day hospitalization at the start of the study for biopsies and blood measurements to determine the level of AZD2171 in the bloodstream. Blood is drawn immediately before the first dose, and 0.25 hr, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, and 48 hours after the dose is taken.

• Blood tests before starting treatment and then monthly to determine the level of vascular endothelial growth factor receptor ( VEGFR), a protein involved in blood vessel formation.

• Magnetic resonance imaging (MRI) scans once a month to evaluate blood flow.

• Tumor biopsies (optional) both before and after the second and sixth treatment cycles.

• Clinic visits every 4 weeks, including various routine and research blood tests, urine test and electrocardiogram.

• Computed tomography (CT) scan of the chest, abdomen, and pelvis every 8 weeks

• Bone scan every 8 weeks

Patients record all doses of AZD2171 taken or missed in a pill diary. They record their blood pressure at least once daily in a blood pressure diary.

Treatment may continue as long as the patient tolerates the AZD2171 and the cancer does not worsen.

...

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Procedure: Magnetic Resonance Imaging (DCE-MRI); Drug: AZD2171; Drug: Prednisone	Phase 2

Detailed Description

Background:

• AZD2171 (Cediranib) is an oral potent inhibitor of receptor tyrosine kinases which impact vascular endothelial growth factor-A (VEGF).

• VEGF appears important in blood vessel formation and disease progression in prostate cancer.

• No known effective therapy in patients with progressive androgen-independent prostate cancer after treatment with docetaxel.

Objectives:

• Primary objective of this study is to determine if AZD2171 is associated with a 30% 6 month probability of progression free survival in patients with metastatic androgen independent prostate cancer (AIPC) as determined by clinical and radiographic criteria.

• Secondary objective of this study will be demonstration of biologic effect by the drug in the patient and on the tumor (when possible). Correlative studies will be conducted on serially obtained tissue biopsies and white blood cell collections.

• Laboratory correlates will include elucidation of activation of components of the VEGFR2 and angiogenesis pathways and evaluation of endothelial cell adhesion molecules (released by damaged cells) using enzyme-linked immunosorbent assay (ELISA), pharmacogenetic analysis of kinase insert domain receptor (KDR) variants and single nucleotide polymorphisms, and pharmacokinetic characterization of AZD2171 activity.

Eligibility:

• Metastatic progressive androgen-independent prostate cancer.

• Prior treatment with docetaxel.

• May not have corrected QT interval (QTc ) greater than 470 msec or greater than 1+ proteinuria on 2 consecutive dipsticks no less than 1 week apart.

Design:

• Phase II trial with a two stage design. 12 patients enrolled in first cohort, if 2 or more are progression free at 6 months than enroll up to 35 evaluable patients. The ceiling will be set at 37 to allow for inevaluable patients.

• Starting dose 20 mg QD (every day) for all patients.

• Once two stage design is complete then prednisone 10 mg once per day will be given in combination with AZD2171. The total number of patients will be 23 for this portion of the protocol.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of AZD2171 in Metastatic Androgen Independent Prostate Cancer
• Actual Study Start Date: Oct 16, 2006
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 5, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD2171 in Prostate Cancer Cohort 1 (n=35) received 20 mg AZD2171 (Cediranib) orally daily. Cohort 2 (n=23) received prednisone 10 mg orally daily with 20 mg AZD2171.	Procedure: Magnetic Resonance Imaging (DCE-MRI); Scans evaluate tumor tissue and blood flow.; Other Names: MRI ; Drug: AZD2171; 20 mg oral daily for 28 days; Other Names: Cediranib ; Drug: Prednisone; 10mg orally daily in combination with AZD2171 20mg daily.; Other Names: Deltasone

Outcome Measures

Primary Outcome Measures

1. Percent Probability of Participants With 6-month Progression-free Survival (PFS) [6 months]

   PFS is the proportion of subjects who progress or die by 6 months after the start of the combined therapy. PFS is determined by prostatic specific antigen (PSA) consensus criteria and the Response Evaluation Criteria in Solid Tumors (RECIST). PSA consensus criteria is defined as PSA decline of >/= 50% or PSA progression. RECIST is defined as the following: Complete response (CR) is disappearance of all target lesions; partial response (PR) is at least a 30% decline in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease ((PD) at least a 20% increase in the sum of the LD of target lesions, or the appearance of one or more lesions), taking as reference the smallest sum LD since the treatment started. Data is estimated and the probability of PFS as a function of time was determined using the Kaplan-Meier method.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [Date treatment consent signed to date off study, approximately 61.5 months]

   Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

2. Number of Grade 2 Toxicities [61.5 months]

   Here is the number of Grade 2 (moderate) toxicities.

3. Number of Grade 3 Toxicities [61.5 months]

   Here is the number of Grade 3 (severe) toxicities.

4. Median Overall Survival [44 months]

   Time from treatment start date until date of death or date last known alive.

5. Median Progression Free Survival (PFS) [up to 14.9 months based on a Kaplan-Meier analysis.]

   Time interval from start of treatment to documented evidence of disease progression.

6. Response Per the Response Evaluation Criteria in Solid Tumors (RECIST) [Every 2 cycles (approximately 56 days)]

   Response was evaluated by the RECIST. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

1. Patients must have histopathological confirmation of prostate cancer by the Laboratory of Pathology of the National Cancer Institute (NCI), Pathology Department of the National Naval Medical Center or Pathology Department of Walter Reed Army Medical Center prior to entering this study. Patients whose pathology specimens are no longer available may be enrolled in the trial if the patient has a clinical course consistent with prostate cancer and available documentation from an outside pathology laboratory of the diagnosis. In cases where original tissue blocks or archival biopsy material is available, all efforts should be made to have the material forwarded to the research team for use in correlative studies.

2. Patients must have metastatic progressive androgen-independent prostate cancer. There must be radiographic evidence of disease that has continued to progress despite hormonal agents. Progression requires that a measurable lesion is expanding, new lesions have appeared, and/or that prostatic specific antigen (PSA) is continuing to rise on successive measurements. Patients on flutamide must have disease progression at least 4 weeks after withdrawal. Patients on bicalutamide or nilutamide must have progression at least 6 weeks after withdrawal.

3. Patients must have received prior therapy with docetaxel for androgen-independent prostate cancer. Any number of prior treatments are acceptable.

4. Age greater than or equal to 18 years.

5. Life expectancy of greater than 3 months.

6. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).

7. Patients must have normal organ and marrow function as defined below:

Absolute neutrophil count greater than or equal to 1,500/mcL

Platelets greater than or equal to 100,000/mcL

Hemoglobin greater than or equal to 8 g/dL

Total bilirubin within normal institutional limits (unless with clinical Gilbert's syndrome)

Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST(SGOT))/alanine aminotransferase/serum glutamic pyruvic transaminase (ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal

Creatinine less than or equal to 1.5 times institutional upper normal institutional limits

OR

Creatinine clearance greater than 40 mL/min/1.3 m^2 for patients with creatinin levels above institutional normal as calculated by the Cockcroft Gault formula.

1. Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.

2. All patients who have not undergone bilateral surgical castration must continue suppression of testosterone production by appropriate usage of gonadotropin releasing hormone (GnRH) agonists or antagonists.

3. Patients must not have other invasive malignancies (within the past three years with the exception of non-melanoma skin cancers or non-invasive bladder cancer).

4. AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 3 months after the end of the treatment.

5. Ability to understand and the willingness to sign a written informed consent document.

6. Patients must have a blood pressure of less than 140/90 at the time of enrollment. Details of antihypertensive treatment, if required, will be left up to the primary care physician.

EXCLUSION CRITERIA:

1. Patients who have had chemotherapy, radiotherapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.

2. Patients may not be receiving any agents not approved by the Food and Drug Administration (FDA) within the past four weeks.

3. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

4. Mean QTc greater than 470 msec (with Bazett's correction) in screening electrocardiogram or history of familial long Q wave, T wave (QT) syndrome.

5. Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart.

6. Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

7. Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: William L Dahut, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol - May 19, 2010
• Informed Consent Form - Dec 4, 2009

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Balbay MD, Pettaway CA, Kuniyasu H, Inoue K, Ramirez E, Li E, Fidler IJ, Dinney CP. Highly metastatic human prostate cancer growing within the prostate of athymic mice overexpresses vascular endothelial growth factor. Clin Cancer Res. 1999 Apr;5(4):783-9.
• Beedassy A, Cardi G. Chemotherapy in advanced prostate cancer. Semin Oncol. 1999 Aug;26(4):428-38. Review.
• Belgore FM, Blann AD, Lip GY. Measurement of free and complexed soluble vascular endothelial growth factor receptor, Flt-1, in fluid samples: development and application of two new immunoassays. Clin Sci (Lond). 2001 May;100(5):567-75.
• Huang J, Jochems C, Talaie T, Anderson A, Jales A, Tsang KY, Madan RA, Gulley JL, Schlom J. Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role. Blood. 2012 Oct 11;120(15):3030-8. doi: 10.1182/blood-2012-05-427799. Epub 2012 Aug 28.

• Responsible Party: William Dahut Jr., M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00436956
• Other Study ID Numbers: 070059; 07-C-0059
• First Posted: Feb 19, 2007
• Last Update Posted: Oct 9, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by William Dahut Jr., M.D., Principal Investigator, National Institutes of Health Clinical Center (CC): VEGF; Angiogenesis; Hormone-Refractory; Bone Metastases; Docetaxel-Resistant; Prostate Cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Cediranib

Study Results

Participant Flow

Arm/Group Title	20 mg AZD2171 Daily	20 mg AZD2171 + 10mg Prednisone Daily
Arm/Group Description	Participants received 20 mg AZD2171 (Cediranib) orally daily.	Participants received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone.
Period Title: Overall Study
STARTED	36	23
COMPLETED	35	23
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	All Participants - AZD2171 & Prednisone
Arm/Group Description	This group combines participants who received 20 mg AZD2171 (Cediranib) orally daily (n=35), in addition to participants who received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone (n=23). One pt was not evaluable due to a cord compression on day 2 of therapy; was removed from the trial (n=1).
Overall Participants	59
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 33.9%
>=65 years	39 66.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68.9
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	59 100%
Race/Ethnicity, Customized (Count of Participants)
Afican-American	3 5.1%
Asian	1 1.7%
White	52 88.1%
Hispanic	3 5.1%
Region of Enrollment (Count of Participants)
United States	59 100%

Outcome Measures

1. Primary Outcome

Title	Percent Probability of Participants With 6-month Progression-free Survival (PFS)
Description	PFS is the proportion of subjects who progress or die by 6 months after the start of the combined therapy. PFS is determined by prostatic specific antigen (PSA) consensus criteria and the Response Evaluation Criteria in Solid Tumors (RECIST). PSA consensus criteria is defined as PSA decline of >/= 50% or PSA progression. RECIST is defined as the following: Complete response (CR) is disappearance of all target lesions; partial response (PR) is at least a 30% decline in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease ((PD) at least a 20% increase in the sum of the LD of target lesions, or the appearance of one or more lesions), taking as reference the smallest sum LD since the treatment started. Data is estimated and the probability of PFS as a function of time was determined using the Kaplan-Meier method.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

One participant was not evaluable owing to the development of a cord compression on day 2 of therapy and was subsequently removed from the trial. Since the prednisone was added to relieve toxicity & outcome data is based on response, the cohorts were analyzed together in terms of response. No suggestion prednisone significantly altered outcomes.

Arm/Group Title	All Participants - AZD2171 & Prednisone
Arm/Group Description	This group combines participants who received 20 mg AZD2171 (Cediranib) orally daily (n=35), in addition to participants who received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone (n=23). One pt was not evaluable due to a cord compression on day 2 of therapy; was removed from the trial (n=1).
Measure Participants	58
Number [percent probability]	43.9

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame	Date treatment consent signed to date off study, approximately 61.5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants- AZD2171 & Prednisone
Arm/Group Description	This group combines participants who received 20 mg AZD2171 (Cediranib) orally daily (n=35), in addition to participants who received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone (n=23). One pt was not evaluable due to a cord compression on day 2 of therapy; was removed from the trial (n=1).
Measure Participants	59
Count of Participants [Participants]	59 100%

3. Secondary Outcome

Title	Number of Grade 2 Toxicities
Description	Here is the number of Grade 2 (moderate) toxicities.
Time Frame	61.5 months

Outcome Measure Data

Analysis Population Description

Only 58 participants were evaluable for toxicity.

Arm/Group Title	20 mg AZD2171 Daily	20 mg AZD2171 + 10mg Prednisone Daily
Arm/Group Description	Participants received 20 mg AZD2171 (Cediranib) orally daily.	Participants received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone.
Measure Participants	35	23
Hypertension	17	8
Fatigue	15	4
Anorexia	12	6
Weight loss	11	4
Hypothyroidism	7	6
Dehydration	8	2
Prolonged QTc	8	2
Nausea	7	3
Diarrhea	8	0
Hypoalbuminemia	5	3
Proteinuria	5	3
Elevated alkaline phosphatase	4	2
Aspartate transaminase	3	3
Vomiting	4	2
Hyperbilirubinemia	4	1
Muscle weakness	2	1

4. Secondary Outcome

Title	Number of Grade 3 Toxicities
Description	Here is the number of Grade 3 (severe) toxicities.
Time Frame	61.5 months

Outcome Measure Data

Analysis Population Description

Only 58 participants were evaluable for toxicity.

Arm/Group Title	20 mg AZD2171 Daily	20 mg AZD2171 + 10mg Prednisone Daily
Arm/Group Description	Participants received 20 mg AZD2171 (Cediranib) orally daily.	Participants received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone.
Measure Participants	35	23
Hypertension	0	0
Fatigue	4	2
Anorexia	1	1
Weight loss	2	0
Hypothyroidism	0	0
Dehydration	3	3
Prolonged QTc	1	1
Nausea	1	0
Diarrhea	0	0
Hypoalbuminemia	0	0
Proteinuria	0	0
Elevated alkaline phosphatase	5	0
Aspartate transaminase	2	0
Vomiting	1	0
Hyperbilirubinemia	1	0
Muscle weakness	3	1

5. Secondary Outcome

Title	Median Overall Survival
Description	Time from treatment start date until date of death or date last known alive.
Time Frame	44 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	20 mg AZD2171 Daily	20 mg AZD2171 + 10mg Prednisone Daily
Arm/Group Description	Participants received 20 mg AZD2171 (Cediranib) orally daily.	Participants received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone.
Measure Participants	35	23
Median (95% Confidence Interval) [Months]	11.7	9.9

6. Secondary Outcome

Title	Median Progression Free Survival (PFS)
Description	Time interval from start of treatment to documented evidence of disease progression.
Time Frame	up to 14.9 months based on a Kaplan-Meier analysis.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	20 mg AZD2171 Daily	20 mg AZD2171 + 10mg Prednisone Daily
Arm/Group Description	Participants received 20 mg AZD2171 (Cediranib) orally daily.	Participants received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone.
Measure Participants	35	23
Median (95% Confidence Interval) [Months]	3.6	3.7

7. Secondary Outcome

Title	Response Per the Response Evaluation Criteria in Solid Tumors (RECIST)
Description	Response was evaluated by the RECIST. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease (PD)is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame	Every 2 cycles (approximately 56 days)

Outcome Measure Data

Analysis Population Description

One patient was not evaluable owing to the development of a cord compression on day 2 of therapy and was subsequently removed from the trial. Out of 59 patients, 39 had measurable disease.

Arm/Group Title	All Participants - AZD2171 & Prednisone
Arm/Group Description	This group combines participants who received 20 mg AZD2171 (Cediranib) orally daily (n=35), in addition to participants who received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone (n=23). One pt was not evaluable due to a cord compression on day 2 of therapy; was removed from the trial (n=1).
Measure Participants	39
Complete Response	0 0%
Confirmed Partial Response	6 10.2%
Unconfirmed Partial Response	1 1.7%
Not Evaluable	1 1.7%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 61.5 months.
Arm/Group Title	All Participants - AZD2171 & Prednisone
Arm/Group Description	This group combines participants who received 20 mg AZD2171 (Cediranib) orally daily (n=35), in addition to participants who received 20 mg AZD2171 (Cediranib) orally daily plus 10mg prednisone (n=23). One pt was not evaluable due to a cord compression on day 2 of therapy; was removed from the trial (n=1).
All Cause Mortality
	All Participants - AZD2171 & Prednisone
	Affected / at Risk (%)	# Events
Total	40/59 (67.8%)
Serious Adverse Events
	All Participants - AZD2171 & Prednisone
	Affected / at Risk (%)	# Events
Total	59/59 (100%)
Blood and lymphatic system disorders
Activated partial thromboplastin time prolonged	4/59 (6.8%)	6
Anemia	15/59 (25.4%)	30
Disseminated intravascular coagulation	2/59 (3.4%)	2
Edema limbs	1/59 (1.7%)	1
INR increased	1/59 (1.7%)	1
Intracranial hemorrhage	1/59 (1.7%)	1
Lymph gland infection	1/59 (1.7%)	1
Lymphocyte count decreased	15/59 (25.4%)	25
Neutrophil count decreased	1/59 (1.7%)	1
Platelet count decreased	6/59 (10.2%)	9
White blood cell decreased	4/59 (6.8%)	4
Cardiac disorders
Cardiac disorders - Other, specify (Prolonged QTc)	1/59 (1.7%)	1
Electrocardiogram QT corrected interval prolonged	12/59 (20.3%)	15
Pericardial effusion	1/59 (1.7%)	1
Pleural effusion	1/59 (1.7%)	1
Ear and labyrinth disorders
Hearing impaired	1/59 (1.7%)	1
Tinnitus	1/59 (1.7%)	1
Endocrine disorders
Hypothyroidism	13/59 (22%)	13
Eye disorders
Blurred vision	2/59 (3.4%)	3
Eye disorders - Other, specify (CRAO)	1/59 (1.7%)	1
Eyelid function disorder	1/59 (1.7%)	1
Optic nerve disorder	1/59 (1.7%)	1
Gastrointestinal disorders
Abdominal pain	2/59 (3.4%)	2
Anorexia	21/59 (35.6%)	22
Constipation	3/59 (5.1%)	3
Dehydration	18/59 (30.5%)	27
Diarrhea	10/59 (16.9%)	11
Dysgeusia	3/59 (5.1%)	3
Dysphasia	2/59 (3.4%)	2
Gum infection	1/59 (1.7%)	1
Mucositis oral	1/59 (1.7%)	2
Nausea	14/59 (23.7%)	16
Oral pain	1/59 (1.7%)	1
Vomiting	8/59 (13.6%)	11
General disorders
Death NOS	40/59 (67.8%)	40
Fatigue	27/59 (45.8%)	37
Fever	2/59 (3.4%)	2
Pain	4/59 (6.8%)	4
Weight loss	19/59 (32.2%)	24
Immune system disorders
Rhinitis infective	1/59 (1.7%)	1
Infections and infestations
Infections and infestations - Other, specify (Infection)	1/59 (1.7%)	2
Joint infection	1/59 (1.7%)	1
Myositis	1/59 (1.7%)	1
Investigations
Investigations - Other, specify (CPK)	1/59 (1.7%)	1
Metabolism and nutrition disorders
Alanine aminotransferase increased	5/59 (8.5%)	6
Alkaline phosphatase increased	21/59 (35.6%)	28
Aspartate aminotransferase increased	12/59 (20.3%)	17
Blood bilirubin increased	6/59 (10.2%)	6
CPK increased	1/59 (1.7%)	1
Creatinine increased	2/59 (3.4%)	2
Hyperglycemia	4/59 (6.8%)	4
Hyperkalemia	5/59 (8.5%)	5
Hypermagnesemia	1/59 (1.7%)	1
Hyperuricemia	2/59 (3.4%)	2
Hypoalbuminemia	14/59 (23.7%)	18
Hypocalcemia	1/59 (1.7%)	1
Hypoglycemia	1/59 (1.7%)	1
Hypokalemia	2/59 (3.4%)	2
Hyponatremia	6/59 (10.2%)	7
Hypophosphatemia	7/59 (11.9%)	7
Proteinuria	8/59 (13.6%)	14
Musculoskeletal and connective tissue disorders
Arthralgia	7/59 (11.9%)	8
Back pain	4/59 (6.8%)	4
Bone pain	12/59 (20.3%)	13
Buttock pain	1/59 (1.7%)	1
Fracture	2/59 (3.4%)	2
Generalized muscle weakness	5/59 (8.5%)	7
Muscle weakness lower limb	4/59 (6.8%)	4
Muscle weakness upper limb	1/59 (1.7%)	1
Pain in extremity	2/59 (3.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	5/59 (8.5%)	5
Nervous system disorders
Ataxia	1/59 (1.7%)	1
Confusion	4/59 (6.8%)	4
Depression	1/59 (1.7%)	1
Dizziness	2/59 (3.4%)	2
Facial nerve disorder	1/59 (1.7%)	1
Headache	1/59 (1.7%)	1
Memory impairment	1/59 (1.7%)	1
Peripheral sensory neuropathy	2/59 (3.4%)	2
Psychosis	2/59 (3.4%)	2
Renal and urinary disorders
Acute kidney injury	1/59 (1.7%)	1
Bladder spasm	1/59 (1.7%)	1
Hematuria	1/59 (1.7%)	1
Urinary retention	1/59 (1.7%)	1
Urinary tract infection	6/59 (10.2%)	6
Urinary tract obstruction	2/59 (3.4%)	2
Urinary tract pain	1/59 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Chest wall pain	2/59 (3.4%)	2
Dyspnea	3/59 (5.1%)	4
Hypoxia	2/59 (3.4%)	2
Lung infection	2/59 (3.4%)	3
Pharyngolaryngeal pain	1/59 (1.7%)	2
Sinus disorder	1/59 (1.7%)	1
Sinusitis	2/59 (3.4%)	2
Upper respiratory infection	1/59 (1.7%)	1
Voice alteration	1/59 (1.7%)	1
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	1/59 (1.7%)	1
Rash maculo-papular	1/59 (1.7%)	1
Skin infection	1/59 (1.7%)	1
Skin ulceration	1/59 (1.7%)	1
Vascular disorders
Hypertension	26/59 (44.1%)	26
Hypotension	6/59 (10.2%)	9
Thromboembolic event	3/59 (5.1%)	3
Venous injury	1/59 (1.7%)	2
Other (Not Including Serious) Adverse Events
	All Participants - AZD2171 & Prednisone
	Affected / at Risk (%)	# Events
Total	56/59 (94.9%)
Blood and lymphatic system disorders
Anemia	7/59 (11.9%)	11
Blood and lymphatic system disorders - Other, specify (Cervical lymh node)	1/59 (1.7%)	1
Edema face	1/59 (1.7%)	1
Edema limbs	1/59 (1.7%)	1
Lymphocyte count decreased	3/59 (5.1%)	3
Oral hemorrhage	1/59 (1.7%)	1
Platelet count decreased	7/59 (11.9%)	8
Rectal hemorrhage	2/59 (3.4%)	2
White blood cell decreased	1/59 (1.7%)	1
Cardiac disorders
Atrioventricular block first degree	1/59 (1.7%)	1
Cardiac disorders - Other, specify (Inverted T waves)	1/59 (1.7%)	1
Electrocardiogram QT corrected interval prolonged	8/59 (13.6%)	8
Paroxysmal atrial tachycardia	1/59 (1.7%)	1
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify (Ear fullness)	1/59 (1.7%)	1
Endocrine disorders
Hot flashes	1/59 (1.7%)	1
Hypothyroidism	16/59 (27.1%)	19
Eye disorders
Blurred vision	1/59 (1.7%)	1
Eye disorders - Other, specify (Opthalmoplegia/diplopia (double Vision))	1/59 (1.7%)	1
Gastrointestinal disorders
Abdominal pain	3/59 (5.1%)	3
Anorexia	15/59 (25.4%)	15
Constipation	5/59 (8.5%)	5
Dehydration	1/59 (1.7%)	1
Diarrhea	35/59 (59.3%)	42
Dry mouth	5/59 (8.5%)	5
Dysgeusia	2/59 (3.4%)	2
Dyspepsia	3/59 (5.1%)	3
Flatulence	2/59 (3.4%)	2
Mucositis oral	2/59 (3.4%)	2
Nausea	14/59 (23.7%)	15
Oral pain	3/59 (5.1%)	3
Vomiting	11/59 (18.6%)	11
General disorders
Chills	1/59 (1.7%)	1
Fatigue	22/59 (37.3%)	25
Fever	2/59 (3.4%)	3
Hyperhidrosis	2/59 (3.4%)	2
Insomnia	3/59 (5.1%)	3
Pain	1/59 (1.7%)	1
Weight loss	21/59 (35.6%)	22
Immune system disorders
Allergic rhinitis	2/59 (3.4%)	2
Infections and infestations
Infections and infestations - Other, specify (Upper resp)	1/59 (1.7%)	1
Metabolism and nutrition disorders
Alanine aminotransferase increased	12/59 (20.3%)	15
Alkaline phosphatase increased	6/59 (10.2%)	6
Aspartate aminotransferase increased	15/59 (25.4%)	17
Blood bilirubin increased	4/59 (6.8%)	4
Creatinine increased	5/59 (8.5%)	6
Hemoglobinuria	2/59 (3.4%)	2
Hyperkalemia	2/59 (3.4%)	2
Hypermagnesemia	1/59 (1.7%)	1
Hyperuricemia	1/59 (1.7%)	1
Hypoalbuminemia	3/59 (5.1%)	4
Hypocalcemia	1/59 (1.7%)	1
Hypokalemia	4/59 (6.8%)	4
Hypomagnesemia	7/59 (11.9%)	7
Hyponatremia	3/59 (5.1%)	3
Proteinuria	13/59 (22%)	16
Musculoskeletal and connective tissue disorders
Arthralgia	8/59 (13.6%)	8
Back pain	1/59 (1.7%)	1
Bone pain	6/59 (10.2%)	6
Generalized muscle weakness	1/59 (1.7%)	1
Muscle weakness lower limb	1/59 (1.7%)	1
Myalgia	2/59 (3.4%)	2
Nervous system disorders
Agitation	1/59 (1.7%)	1
Confusion	3/59 (5.1%)	3
Depression	2/59 (3.4%)	2
Dizziness	12/59 (20.3%)	13
Extrapyramidal disorder	1/59 (1.7%)	1
Glossopharyngeal nerve disorder	1/59 (1.7%)	1
Headache	12/59 (20.3%)	13
Nervous system disorders - Other, specify (Staring spells)	1/59 (1.7%)	1
Peripheral sensory neuropathy	3/59 (5.1%)	3
Renal and urinary disorders
Hematuria	4/59 (6.8%)	4
Urinary frequency	6/59 (10.2%)	6
Urinary incontinence	1/59 (1.7%)	1
Urinary tract obstruction	2/59 (3.4%)	2
Reproductive system and breast disorders
Breast pain	1/59 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Chest wall pain	2/59 (3.4%)	2
Cough	4/59 (6.8%)	4
Dyspnea	4/59 (6.8%)	4
Forced expiratory volume decreased	2/59 (3.4%)	2
Pharyngolaryngeal pain	1/59 (1.7%)	1
Pleural effusion	3/59 (5.1%)	4
Respiratory, thoracic and mediastinal disorders - Other, specify (Rhinorrhea)	1/59 (1.7%)	1
Sinus disorder	2/59 (3.4%)	3
Voice alteration	15/59 (25.4%)	16
Skin and subcutaneous tissue disorders
Bruising	1/59 (1.7%)	1
Dry skin	1/59 (1.7%)	1
Flushing	1/59 (1.7%)	1
Nail loss	1/59 (1.7%)	1
Rash maculo-papular	2/59 (3.4%)	2
Vascular disorders
Hypertension	6/59 (10.2%)	6
Hypotension	1/59 (1.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.