Bevacizumab Beyond Progression (BBP)

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01740258
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 68
• Location: 1
• Arm: 1
• Actual Duration (Months): 82.4
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Studies which have separately studied bevacizumab for recurrent gliomas and bevacizumab for newly-diagnosed glioma have shown good results and the regimens have been well-tolerated by patients. This study seeks to investigate the use of bevacizumab with the standard therapy (radiation therapy and temozolomide) in newly diagnosed patients, followed by bevacizumab and temozolomide with the continuation of bevacizumab following progression. Two critical questions remain- the role of bevacizumab maintenance and bevacizumab at the time of progression in a patient previously treated with bevacizumab at the time of initial diagnosis.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma; Grade 4 Malignant Glioma; Glioblastoma; Gliosarcoma	Radiation: Radiation Therapy; Drug: Temozolomide; Drug: Bevacizumab	Phase 2

Detailed Description

Given the possible synergism with irinotecan and bevacizumab for colorectal carcinomas, the combination has been studied in gliomas. In a study of 21 patients, the combination of irinotecan and bevacizumab produced a 43% response rate, with acceptable toxicity. The response rate is significantly higher than irinotecan alone and any other therapy for recurrent glioma. There were two serious adverse events, one intracranial hemorrhage and one bowel perforation. At the Duke Brain Tumor Center, the investigators have treated over 1000 glioblastoma patients with a bevacizumab-containing regimen, and there is marked clinical benefit and acceptable toxicity. Our initial study looking at the combination of bevacizumab and irinotecan for patients with recurrent glioblastoma published in 2007 found impressive response rates and survival and corroborated the earlier experience of Starks-Vance.

The investigators completed a study for newly diagnosed glioblastoma that utilized bevacizumab, radiation therapy and temozolomide followed by 6 months of bevacizumab, irinotecan and temozolomide. In addition, the group at University of California at Los Angeles published a study with bevacizumab, radiation therapy and temozolomide followed by 12 months of bevacizumab and temozolomide for newly diagnosed glioblastoma. These two phase II studies reported acceptable toxicity and a suggestion of improved survival compared to historical controls, and led to two large phase III randomized, placebo controlled studies of the addition of bevacizumab for newly diagnosed glioblastoma patients. The current proposal builds on the encouraging results of the addition of bevacizumab to the standard therapy for newly diagnosed glioblastoma patients. Two critical questions remain- the role of bevacizumab maintenance and bevacizumab at the time of progression in a patient previously treated with bevacizumab at the time of initial diagnosis. In addition, a retrospective analysis of data collected at our center from patients with recurrent disease suggests that continuation of bevacizumab at the time of progression may improve overall survival in comparison with cessation of bevacizumab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Bevacizumab, Radiation Therapy and Temodar Followed by Bevacizumab and Temodar With Continuation of Bevacizumab Beyond Progression (BBP-Bevacizumab Beyond Progression)
• Actual Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Nov 14, 2019
• Actual Study Completion Date: Nov 14, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Bevaczimab, Radiation Therapy, Temozolomide In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician.

Radiation: Radiation Therapy; Other Names: XRT ; Drug: Temozolomide; Other Names: temo temodar ; Drug: Bevacizumab; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Overall Survival [5 Years]

   To assess the effect on overall survival of continuing bevacizumab treatment after disease progression in patients treated with bevacizumab from the time of first diagnosis of grade IV malignant glioma.

Secondary Outcome Measures

1. Toxicity: Percentage of Subjects With Unacceptable Toxicities [5 Years]

   The occurrence of ≥ grade 2 CNS (central nervous system) hemorrhage or grade 4 or 5 non-hematologic toxicity is defined as being unacceptable. "Unacceptable" toxicity rates of 5% or less are considered desirable, while rates of 20% or greater are considered as undesirable.

2. Progression-free Survival (PFS) [5 Years]

   To assess the effect on progression-free survival of continuing bevacizumab treatment after disease progression in patients treated with bevacizumab from the time of initiation of treatment to the first occurrence of progression, or death

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with histologically confirmed WHO Grade IV primary malignant glioma (glioblastoma or gliosarcoma);

• Patients ≥ 18 years of age;

• An interval of at least 2 weeks, but not ≥ 8 weeks between prior surgical procedure and initiation of treatment;

• Karnofsky Performance Status (KPS) ≥ 60%

• Laboratory Values:

• Platelet Count ≥ 125,000 cells/µL

• Absolute neutrophil count (ANC) ≥ 1,500 cells/µL

• Adequate renal function indicated by all of the following:

• Serum creatinine ≤ 1.25 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 ml/min

• Urine dipstick for proteinuria < 2+ unless a 24-hour urine protein < 1 g of protein is demonstrated

• internationalized normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x upper limit of normal (ULN) within 7 days prior to first study treatment for patients not receiving anti-coagulation. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least two weeks prior to the first study treatment.

• Patients will sign an Institutional Review Board-approved informed consent form.

• Female patients must not be pregnant or breast-feeding. Female patients of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, [i.e. with a failure rate of < 1% per year] are implants, injectables, combined oral contraceptives, intra-uterine device [Intrauterine Device (IUD); only hormonal], sexual abstinence or vasectomized partner) during the trial and for a period of > 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy test within 7 days prior to first study treatment.

• Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control [i.e. with a failure rate of < 1% per year] include a female partner using implants, injectables, combined oral contraceptives, Intrauterine Device (IUDs) [only hormonal], sexual abstinence or prior vasectomy) during the trial and for a period of > 6 months following the last administration of trial drugs.

Exclusion Criteria:

• Any prior treatment for any grade glioma, including, but not limited to gliadel wafers, immunotherapy (including vaccine therapy), radiation therapy or chemotherapy, irrespective of grade of the tumor (NOTE: 5-aminolevulinic acid (ALA)-mediated photodynamic therapy administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent.);

• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;

• Active infection requiring intravenous antibiotics;

• Prior or current treatment with bevacizumab or other anti-angiogenic treatment (i.e. anti-vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) therapies or tyrosine kinase inhibitors) for any condition;

• Treatment with any other investigational agent within 28 days or 2 investigational agent half-lives (whichever is longer) prior to first study treatment;

• Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;

• Evidence of > Grade 1 central nervous system (CNS) hemorrhage on post-operative MRI scan, unless repeat MRI or CT performed prior to initiating bevacizumab shows stable grade 1 or resolving (< grade 1) CNS hemorrhage.

Bevacizumab-Specific Exclusion Criteria:

• Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) within 28 days of first study treatment;

• Prior history of hypertensive crisis, hypertensive encephalopathy, reverse posterior leukoencephalopathy syndrome (RPLS);

• Prior history of gastrointestinal perforation or abscess;

• Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment;

• History or evidence upon physical/neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer unless adequately controlled by medication or potentially interfering with protocol treatment;

• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment. Any previous venous thromboembolism > NCI common toxicity criteria adverse event (CTCAE) Grade 3;

• History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 1 month of first study treatment;

• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation);

• Current or recent (within 10 days of study enrollment) use of aspirin (>325 mg/day), clopidogrel (>75 mg/day) or equivalent. Prophylactic use of anticoagulants is allowed;

• Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to first study treatment, or anticipation of need for major surgical procedure during the course of the study;

• Minor surgical procedure, e.g. stereotactic biopsy, within 7 days of first study treatment; placement of a vascular access device, within 2 days of first study treatment;

• History of intracranial abscess within 6 months prior to first study treatment;

• History of active gastrointestinal bleeding within 6 months prior to first study treatment;

• Serious, non-healing wound, active ulcer, or untreated bone fracture;

• Known hypersensitivity to any component of bevacizumab or any of the study drugs;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Cancer Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• Genentech, Inc.

Investigators

• Principal Investigator: Annick Desjardins, MD, FRCPC, Duke Health

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 9, 2016

More Information

Additional Information:

• Preston Robert Tisch Brain Tumor Center at Duke
• Duke Cancer Institute
• Duke Cancer Center - Patient Care

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01740258
• Other Study ID Numbers: Pro00038098
• First Posted: Dec 4, 2012
• Last Update Posted: Jan 26, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Duke University: malignant glioma; Grade 4 malignant glioma; glioblastoma; gliosarcoma; adult brain tumor
• Additional relevant MeSH terms: Glioblastoma; Glioma; Gliosarcoma; Bevacizumab; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Bevaczimab, Radiation Therapy, Temozolomide
Arm/Group Description	In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician. Radiation Therapy Temozolomide Bevacizumab
Period Title: Overall Study
STARTED	68
Entered Part A	68
Entered Part B	62
Entered Part C	20
Entered Part D	42
COMPLETED	68
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bevaczimab, Radiation Therapy, Temozolomide
Arm/Group Description	In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician. Radiation Therapy Temozolomide Bevacizumab
Overall Participants	68
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.43 (10.68)
Sex: Female, Male (Count of Participants)
Female	21 30.9%
Male	47 69.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.5%
Not Hispanic or Latino	67 98.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 2.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2.9%
White	64 94.1%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	68 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	To assess the effect on overall survival of continuing bevacizumab treatment after disease progression in patients treated with bevacizumab from the time of first diagnosis of grade IV malignant glioma.
Time Frame	5 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevaczimab, Radiation Therapy, Temozolomide
Arm/Group Description	In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician. Radiation Therapy Temozolomide Bevacizumab
Measure Participants	68
Median (95% Confidence Interval) [months]	17.8

2. Secondary Outcome

Title	Toxicity: Percentage of Subjects With Unacceptable Toxicities
Description	The occurrence of ≥ grade 2 CNS (central nervous system) hemorrhage or grade 4 or 5 non-hematologic toxicity is defined as being unacceptable. "Unacceptable" toxicity rates of 5% or less are considered desirable, while rates of 20% or greater are considered as undesirable.
Time Frame	5 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevaczimab, Radiation Therapy, Temozolomide
Arm/Group Description	In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician. Radiation Therapy Temozolomide Bevacizumab
Measure Participants	68
Number [percentage of participants]	11.8 17.4%

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	To assess the effect on progression-free survival of continuing bevacizumab treatment after disease progression in patients treated with bevacizumab from the time of initiation of treatment to the first occurrence of progression, or death
Time Frame	5 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevaczimab, Radiation Therapy, Temozolomide
Arm/Group Description	In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician. Radiation Therapy Temozolomide Bevacizumab
Measure Participants	68
Median (95% Confidence Interval) [months]	9.9

Adverse Events

Time Frame	5 years
Arm/Group Title	Bevaczimab, Radiation Therapy, Temozolomide
Arm/Group Description	In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician. Radiation Therapy Temozolomide Bevacizumab
All Cause Mortality
	Bevaczimab, Radiation Therapy, Temozolomide
	Affected / at Risk (%)	# Events
Total	68/68 (100%)
Serious Adverse Events
	Bevaczimab, Radiation Therapy, Temozolomide
	Affected / at Risk (%)	# Events
Total	41/68 (60.3%)
Blood and lymphatic system disorders
Anemia	2/68 (2.9%)
Febrile neutropenia	2/68 (2.9%)
Cardiac disorders
Acute coronary syndrome	1/68 (1.5%)
Myocardial infarction	1/68 (1.5%)
Gastrointestinal disorders
Colonic perforation	1/68 (1.5%)
Duodenal obstruction	1/68 (1.5%)
Dysphagia	1/68 (1.5%)
Gastric hemorrhage	1/68 (1.5%)
Nausea	2/68 (2.9%)
Vomiting	1/68 (1.5%)
General disorders
Death NOS	8/68 (11.8%)
Fatigue	2/68 (2.9%)
Fever	5/68 (7.4%)
Gait disturbance	1/68 (1.5%)
Localized edema	1/68 (1.5%)
Hepatobiliary disorders
Cholecystitis	1/68 (1.5%)
Immune system disorders
Allergic reaction	1/68 (1.5%)
Infections and infestations
Infections and infestations - Other, specify: R PERI-TONSILLAR ABSCESS; CPT-11	1/68 (1.5%)
Infections and infestations - Other, specify: ULCERATIVE VIRAL L TONSILLITIS	1/68 (1.5%)
Infections and infestations - Other, specify: VIRAL SEPSIS SYNDROME	1/68 (1.5%)
Lung infection	3/68 (4.4%)
Rash pustular	1/68 (1.5%)
Sepsis	2/68 (2.9%)
Skin infection	1/68 (1.5%)
Urinary tract infection	1/68 (1.5%)
Wound infection	1/68 (1.5%)
Investigations
Alanine aminotransferase increased	1/68 (1.5%)
Neutrophil count decreased	4/68 (5.9%)
Platelet count decreased	8/68 (11.8%)
White blood cell decreased	2/68 (2.9%)
Metabolism and nutrition disorders
Anorexia	1/68 (1.5%)
Dehydration	2/68 (2.9%)
Hypocalcemia	1/68 (1.5%)
Hyponatremia	1/68 (1.5%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	3/68 (4.4%)
Nervous system disorders
Ataxia	1/68 (1.5%)
Dysphasia	2/68 (2.9%)
Encephalopathy	2/68 (2.9%)
Headache	2/68 (2.9%)
Intracranial hemorrhage	1/68 (1.5%)
Pyramidal tract syndrome	6/68 (8.8%)
Seizure	15/68 (22.1%)
Stroke	2/68 (2.9%)
Psychiatric disorders
Confusion	1/68 (1.5%)
Delirium	3/68 (4.4%)
Renal and urinary disorders
Proteinuria	7/68 (10.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/68 (1.5%)
Pneumonitis	1/68 (1.5%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/68 (1.5%)
Vascular disorders
Hypertension	7/68 (10.3%)
Thromboembolic event	4/68 (5.9%)
Other (Not Including Serious) Adverse Events
	Bevaczimab, Radiation Therapy, Temozolomide
	Affected / at Risk (%)	# Events
Total	68/68 (100%)
Blood and lymphatic system disorders
Anemia	45/68 (66.2%)
Cardiac disorders
Chest pain - cardiac	1/68 (1.5%)
Conduction disorder	1/68 (1.5%)
Mitral valve disease	1/68 (1.5%)
Sinus bradycardia	1/68 (1.5%)
Sinus tachycardia	1/68 (1.5%)
Ventricular tachycardia	1/68 (1.5%)
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify: FULLNESS IN LEFT EAR-RADIATION	1/68 (1.5%)
Ear and labyrinth disorders - Other, specify: L EAR CLOGGED; XRT	1/68 (1.5%)
Ear and labyrinth disorders - Other, specify: WAX IMPACTION	1/68 (1.5%)
Ear pain	2/68 (2.9%)
Hearing impaired	1/68 (1.5%)
Tinnitus	1/68 (1.5%)
Vertigo	1/68 (1.5%)
Endocrine disorders
Endocrine disorders - Other, specify: HYPOTESTOSTERONEMIA	1/68 (1.5%)
Eye disorders
Blurred vision	10/68 (14.7%)
Cataract	1/68 (1.5%)
Dry eye	2/68 (2.9%)
Eye disorders - Other, specify: DIPLOPIA	1/68 (1.5%)
Eye disorders - Other, specify: EYE STRAIN	1/68 (1.5%)
Eye disorders - Other, specify: FLOATER VS. SMUDGE; XRT	1/68 (1.5%)
Eye disorders - Other, specify: HOMONYMOUS HEMIANOPSIA; RIGHT EYE	1/68 (1.5%)
Eye disorders - Other, specify: L EYE TWITCH FROM EYE STRAIN	1/68 (1.5%)
Eye disorders - Other, specify: L HOMONYMOUS HEMIANOPSIA	2/68 (2.9%)
Eye disorders - Other, specify: MOMENTARY LOSS OF VISION IN L EYE	1/68 (1.5%)
Eye disorders - Other, specify: OPTIC NERVE NEUROPATHY; AVASTIN	1/68 (1.5%)
Eye disorders - Other, specify: PERIPHERAL VISION LOSS	1/68 (1.5%)
Eye disorders - Other, specify: R VISUAL FIELD CUT	1/68 (1.5%)
Eye disorders - Other, specify: R VISUAL FIELD CUT, DISEASE PROGRESSION	1/68 (1.5%)
Eye disorders - Other, specify: RU QUADRANOPSIA	2/68 (2.9%)
Photophobia	1/68 (1.5%)
Gastrointestinal disorders
Abdominal pain	8/68 (11.8%)
Anal hemorrhage	3/68 (4.4%)
Constipation	49/68 (72.1%)
Dental caries	3/68 (4.4%)
Diarrhea	33/68 (48.5%)
Dry mouth	2/68 (2.9%)
Dyspepsia	6/68 (8.8%)
Dysphagia	4/68 (5.9%)
Fecal incontinence	7/68 (10.3%)
Flatulence	4/68 (5.9%)
Gastritis	1/68 (1.5%)
Gastroesophageal reflux disease	3/68 (4.4%)
Gastrointestinal disorders - Other, specify: ABSCESSED WISDOM TOOTH	1/68 (1.5%)
Gastrointestinal disorders - Other, specify: CHIPPED TOOTH	2/68 (2.9%)
Gastrointestinal disorders - Other, specify: RECTAL BLEEDING; AVASTIN	1/68 (1.5%)
Gingival pain	2/68 (2.9%)
Hemorrhoidal hemorrhage	2/68 (2.9%)
Hemorrhoids	5/68 (7.4%)
Mucositis oral	16/68 (23.5%)
Nausea	42/68 (61.8%)
Oral hemorrhage	3/68 (4.4%)
Periodontal disease	2/68 (2.9%)
Rectal hemorrhage	2/68 (2.9%)
Toothache	2/68 (2.9%)
Vomiting	23/68 (33.8%)
General disorders
Chills	1/68 (1.5%)
Death NOS	11/68 (16.2%)
Edema limbs	12/68 (17.6%)
Fatigue	63/68 (92.6%)
Fever	13/68 (19.1%)
Flu like symptoms	5/68 (7.4%)
Gait disturbance	4/68 (5.9%)
Other, specify: DUE TO STEROIDS, INTERMITTENT DIAPHORESIS, LIGHTHEADEDNESS AND HYPERTENSION	1/68 (1.5%)
General disorders and administration site conditions - Other, specify: FEELS COLD	1/68 (1.5%)
Infusion site extravasation	1/68 (1.5%)
Injection site reaction	1/68 (1.5%)
Irritability	4/68 (5.9%)
Localized edema	1/68 (1.5%)
Neck edema	1/68 (1.5%)
Non-cardiac chest pain	2/68 (2.9%)
Pain	10/68 (14.7%)
Hepatobiliary disorders
Gallbladder obstruction	1/68 (1.5%)
Immune system disorders
Allergic reaction	4/68 (5.9%)
Infections and infestations
Bronchial infection	1/68 (1.5%)
Infections and infestations - Other, specify: COLD SORES	1/68 (1.5%)
Infections and infestations - Other, specify: GOUT	1/68 (1.5%)
Infections and infestations - Other, specify: LYME'S DX	1/68 (1.5%)
Infections and infestations - Other, specify: RLE CELLULITIS	1/68 (1.5%)
Infections and infestations - Other, specify: SHINGLES	3/68 (4.4%)
Infections and infestations - Other, specify: TRIGEMINAL HERPES ZOSTER	1/68 (1.5%)
Infections and infestations - Other, specify: ULCERATIVE VIRAL L TONSILLITIS	1/68 (1.5%)
Lung infection	1/68 (1.5%)
Lymph gland infection	1/68 (1.5%)
Mucosal infection	1/68 (1.5%)
Nail infection	1/68 (1.5%)
Otitis externa	1/68 (1.5%)
Otitis media	1/68 (1.5%)
Papulopustular rash	2/68 (2.9%)
Pharyngitis	1/68 (1.5%)
Sinusitis	11/68 (16.2%)
Skin infection	4/68 (5.9%)
Tooth infection	2/68 (2.9%)
Upper respiratory infection	10/68 (14.7%)
Urinary tract infection	10/68 (14.7%)
Vaginal infection	1/68 (1.5%)
Injury, poisoning and procedural complications
Bruising	1/68 (1.5%)
Dermatitis radiation	4/68 (5.9%)
Fall	10/68 (14.7%)
Fracture	2/68 (2.9%)
Injury, poisoning and procedural complications - Other, specify: ABDOMINAL BRUISING AT INJECTION	1/68 (1.5%)
Injury, poisoning and procedural complications - Other, specify: BRUISING ON RIGHT THUMB	1/68 (1.5%)
Injury, poisoning and procedural complications - Other, specify: HAND PUNCTURE	1/68 (1.5%)
Wound complication	2/68 (2.9%)
Investigations
Alanine aminotransferase increased	41/68 (60.3%)
Alkaline phosphatase increased	16/68 (23.5%)
Aspartate aminotransferase increased	37/68 (54.4%)
Blood bilirubin increased	18/68 (26.5%)
Cholesterol high	1/68 (1.5%)
Creatinine increased	18/68 (26.5%)
Lymphocyte count decreased	53/68 (77.9%)
Neutrophil count decreased	45/68 (66.2%)
Platelet count decreased	59/68 (86.8%)
Weight gain	2/68 (2.9%)
Weight loss	4/68 (5.9%)
White blood cell decreased	51/68 (75%)
Metabolism and nutrition disorders
Anorexia	18/68 (26.5%)
Dehydration	7/68 (10.3%)
Hyperglycemia	60/68 (88.2%)
Hyperkalemia	14/68 (20.6%)
Hypermagnesemia	2/68 (2.9%)
Hypernatremia	14/68 (20.6%)
Hypoalbuminemia	29/68 (42.6%)
Hypocalcemia	34/68 (50%)
Hypoglycemia	22/68 (32.4%)
Hypokalemia	31/68 (45.6%)
Hypomagnesemia	3/68 (4.4%)
Hyponatremia	37/68 (54.4%)
Hypophosphatemia	3/68 (4.4%)
Metabolism and nutrition disorders - Other, specify: STEROID INDUCED DIABETES	1/68 (1.5%)
Metabolism and nutrition disorders - Other, specify: VITAMIN B12 DEFICIENCY	1/68 (1.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	30/68 (44.1%)
Arthritis	3/68 (4.4%)
Back pain	8/68 (11.8%)
Flank pain	1/68 (1.5%)
Generalized muscle weakness	8/68 (11.8%)
Joint range of motion decreased	1/68 (1.5%)
Muscle weakness lower limb	5/68 (7.4%)
Muscle weakness upper limb	1/68 (1.5%)
Musculoskeletal and connective tissue disorder - Other, specify: ADHESIVE CAPSULITIS	1/68 (1.5%)
Musculoskeletal and connective tissue disorder - Other, specify: BILATERAL LEG CRAMPING	1/68 (1.5%)
Musculoskeletal and connective tissue disorder - Other, specify: CALF CRAMPS	1/68 (1.5%)
Musculoskeletal and connective tissue disorder - Other, specify: HARD BONY SWELLING ON LEFT HEEL	1/68 (1.5%)
Other, specify: INTERMITTENT PAIN IN R GROIN & CALF	1/68 (1.5%)
Other, specify: L SHOULDER PARTIAL THICKNESS TEAR, BURSITIS	1/68 (1.5%)
Musculoskeletal and connective tissue disorder - Other, specify: MUSCLE INJURY	1/68 (1.5%)
Other, specify: PAIN FROM HISTORICAL SPORTS INJURIES IN EXTREMITIES	1/68 (1.5%)
Musculoskeletal and connective tissue disorder - Other, specify: STEROID MYOPATHY	1/68 (1.5%)
Myalgia	9/68 (13.2%)
Neck pain	3/68 (4.4%)
Pain in extremity	4/68 (5.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	4/68 (5.9%)
Nervous system disorders
Cognitive disturbance	2/68 (2.9%)
Concentration impairment	2/68 (2.9%)
Dizziness	6/68 (8.8%)
Dysarthria	8/68 (11.8%)
Dysgeusia	19/68 (27.9%)
Dysphasia	17/68 (25%)
Encephalopathy	1/68 (1.5%)
Extrapyramidal disorder	4/68 (5.9%)
Headache	43/68 (63.2%)
Hypersomnia	1/68 (1.5%)
Intracranial hemorrhage	2/68 (2.9%)
Lethargy	1/68 (1.5%)
Memory impairment	27/68 (39.7%)
Nervous system disorders - Other, specify: ANOMIA	1/68 (1.5%)
Nervous system disorders - Other, specify: DYSMETRIA	1/68 (1.5%)
Nervous system disorders - Other, specify: GAIT UNSTEADINESS	1/68 (1.5%)
Nervous system disorders - Other, specify: PERIPHERAL NERVE COMPRESSION - R FOOT	1/68 (1.5%)
Neuralgia	2/68 (2.9%)
Paresthesia	14/68 (20.6%)
Pyramidal tract syndrome	17/68 (25%)
Radiculitis	2/68 (2.9%)
Seizure	31/68 (45.6%)
Sinus pain	1/68 (1.5%)
Somnolence	1/68 (1.5%)
Stroke	2/68 (2.9%)
Tremor	7/68 (10.3%)
Psychiatric disorders
Agitation	2/68 (2.9%)
Anxiety	6/68 (8.8%)
Confusion	8/68 (11.8%)
Depression	8/68 (11.8%)
Hallucinations	2/68 (2.9%)
Insomnia	11/68 (16.2%)
Renal and urinary disorders
Chronic kidney disease	1/68 (1.5%)
Hematuria	5/68 (7.4%)
Proteinuria	46/68 (67.6%)
Renal and urinary disorders - Other, specify: BLADDER PRESSURE	1/68 (1.5%)
Renal and urinary disorders - Other, specify: BLADDER SPASMS	1/68 (1.5%)
Urinary frequency	3/68 (4.4%)
Urinary incontinence	9/68 (13.2%)
Urinary retention	2/68 (2.9%)
Urinary tract pain	1/68 (1.5%)
Urinary urgency	2/68 (2.9%)
Reproductive system and breast disorders
Breast pain	1/68 (1.5%)
Dyspareunia	1/68 (1.5%)
Irregular menstruation	1/68 (1.5%)
Reproductive system and breast disorders - Other, specify: ABNORMAL PAP SMEAR	1/68 (1.5%)
Reproductive system and breast disorders - Other, specify: ATYPICAL DUCTAL HYPERPLASIA - LEFT BREAST	1/68 (1.5%)
Vaginal discharge	1/68 (1.5%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/68 (4.4%)
Aspiration	1/68 (1.5%)
Cough	15/68 (22.1%)
Dyspnea	6/68 (8.8%)
Epistaxis	20/68 (29.4%)
Hiccups	2/68 (2.9%)
Hoarseness	13/68 (19.1%)
Nasal congestion	8/68 (11.8%)
Postnasal drip	51/68 (75%)
Productive cough	1/68 (1.5%)
Sneezing	1/68 (1.5%)
Sore throat	8/68 (11.8%)
Voice alteration	2/68 (2.9%)
Skin and subcutaneous tissue disorders
Alopecia	24/68 (35.3%)
Dry skin	13/68 (19.1%)
Hyperhidrosis	2/68 (2.9%)
Nail ridging	1/68 (1.5%)
Pruritus	3/68 (4.4%)
Rash acneiform	8/68 (11.8%)
Rash maculo-papular	13/68 (19.1%)
Skin and subcutaneous tissue disorders - Other, specify: BASAL CELL CARCINOMA REMOVAL	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: BILATERAL FOREARMS BRUISING, INTERMITTENT	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: BIOPSY OF SCAB IN SITU LEFT NOSE	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: CALLOUS PATCHES BILATERAL FEET	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: CALLUS-LIKE FORMATION ON FOOT SKIN GRAFTS	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: DELAYED WOUND HEALING; AVASTIN	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: ECZEMATOUS DERMATITIS L FOREARM	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: HIVES ON R FLANK - DUE TO STRESS	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: HIVES/RASH	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: HYPERPIGMENTED SKIN LESIONS; CARBOPLATIN	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: I&D OF MID-BACK BOIL	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: LACERATION REQUIRING SUTURES	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: LEFT LE SKIN LESION S/P PUNCH BIOPSY	1/68 (1.5%)
Other, specify: MILD ERYTHEMA AROUND THE RIGHT BACKSIDE WITH QUESTIONING RESOLVING IMPETIGO.	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: MULTIPLE ABRASIONS FROM FALL	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: NON-INFECTED INGROWN TOENAIL	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: PETECHIAE B/L THIGHS; AVASTIN	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: PIMPLE/BUG BITE	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: R AND L PLANTAR CALLUSES	1/68 (1.5%)
Other, specify: R HAND SMALL SKIN TEAR; SECONDARY TO LONG TERM STEROID USE	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: REDNESS FROM TICK BITE	1/68 (1.5%)
Other, specify: REDNESS/FLUSHING OF FACE; POSSIBLY DUE TO STEROIDS	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: SCALP FOLLICULITIS	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: SKIN TEAR/BRUISING LEFT ELBOW	1/68 (1.5%)
Skin and subcutaneous tissue disorders - Other, specify: SQUAMOUS CELL CARCINOMA ON NOSE	1/68 (1.5%)
Skin ulceration	1/68 (1.5%)
Vascular disorders
Hematoma	1/68 (1.5%)
Hot flashes	1/68 (1.5%)
Hypertension	39/68 (57.4%)
Hypotension	3/68 (4.4%)
Phlebitis	1/68 (1.5%)
Thromboembolic event	7/68 (10.3%)
Vascular disorders - Other, specify: BILATERAL LE CLAUDICATION	1/68 (1.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.