AMG 102 and Avastin for Recurrent Malignant Glioma

• Sponsor: Katy Peters (Other)
• Overall Status: Completed
• CT.gov ID: NCT01113398
• Collaborator: Amgen (Industry)
• Enrollment: 36
• Location: 1
• Arm: 1
• Duration (Months): 61
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The primary purpose of the study is to assess the response rate of AMG 102 and Avastin treatment in subjects with advanced malignant glioma. Secondary objectives are to estimate overall survival and 6-month progression-free survival rates in this population and to assess the safety of this combination in this population.

Patients must have recurrent histologically confirmed diagnosis of World Health Organization (WHO) grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with no more than 3 prior progressions. Subjects will receive Avastin and AMG 102 every two weeks. Avastin will be administered prior to AMG 102. Up to 36 adult subjects will take part in this study at Duke.

In initial Phase I and II clinical trials, four potential Avastin-associated safety issues were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. The most common side effect for AMG 102 have been nausea and fatigue.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme; Gliosarcoma	Drug: AMG 102; Drug: Avastin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study to Evaluate the Efficacy and Safety of AMG 102 and Avastin in Subjects With Recurrent Malignant Glioma
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 102 with Avastin Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks.	Drug: AMG 102; AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes.; Other Names: rilotumumab ; Drug: Avastin; Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.; Other Names: Bevacizumab

Outcome Measures

Primary Outcome Measures

1. Radiographic Response [2 years]

   The percentage of participants with a complete or partial response as determined by modified Response Assessment in Neuro-Oncology (RANO) criteria will be determined. Complete Response (CR) is defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) is defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Tumor assessments are done at baseline and the end of every 6-week cycle thereafter.

Secondary Outcome Measures

1. Median Overall Survival (OS) [2 years]

   Overall survival is defined as the time in months from the start of protocol treatment until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.

2. Six-month Progression-free Survival (PFS6) [6 months]

   The percentage of participants alive and progression-free at 6 months after the start of study treatment will be determined. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.

3. Percentage of Participants Who Experience Treatment-related Grade 2 or Greater CNS Hemorrhage or Grade 4 or Greater Non-hematologic Toxicities [2 years]

   The percentage of participants who experience unacceptable toxicity, defined as any treatment-related grade 2 or greater CNS hemorrhage or grade 4 or greater non-hematologic toxicity, will be calculated.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have recurrent histologically confirmed diagnosis of WHO grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with no more than 3 prior progressions.

• Age ≥ 18 years.

• Karnofsky ≥ 60%.

• An interval of at least 4 weeks between either prior tumor biopsy or prior major surgical procedure and study enrollment.

• Bi-dimensionally measurable disease as assessed by magnetic resonance imaging.

• Hemoglobin ≥9.0 g/dl, ANC ≥1500 cells/µl, Platelets ≥125,000 cells/µl (without transfusion within 14 days before enrollment).

• Serum creatinine < 1.5 mg/dl, bilirubin < 1.5 times upper limit of normal, and serum SGOT (AST) and SGPT (ALT) < 2.5 times upper limit of normal.

• For patients on corticosteroids, they must be on a stable dose for 1 week prior to entry, and the dose should not be escalated over entry dose level, if clinically possible.

• Signed informed consent approved by the Institutional Review Board.

• No evidence of active CNS hemorrhage on the baseline MRI or CT scan.

• If sexually active, patients will take contraceptive measures for the duration of treatment as stated in the informed consent.

Exclusion Criteria:

• Pregnancy or breast-feeding.

• Baseline ECG with QTc > 0.45 second

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

• Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction.

• Active infection requiring IV antibiotics 7 days before enrollment.

• History of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) within 6 months before enrollment.

• Evidence of acute intracranial hemorrhage; except for subjects with stable grade 1 hemorrhage.

• Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 consecutive scans or histopathologic confirmation.

• Treated previously with any c-Met or HGF targeted therapy.

• Treated previously with VEGF or VEGFR therapies, including antibodies and tyrosine kinase inhibitors.

• Treated with thalidomide or tamoxifen within 1 week before enrollment unless the patient has recovered from the toxic effects of such therapy.

• Treated with immunotherapeutic agents, vaccines, or MAb therapy within 4 weeks before enrollment unless the patient has recovered from the toxic effects of such therapy.

• Treated with alkylating agents within 4 weeks before enrollment or if the patient has been treated with daily or metronomic chemotherapy unless the patient has recovered from the toxic effects of such therapy.

• Treated with chemotherapy (non-alkylating agents) within 2 weeks before enrollment unless the patient has recovered from the toxic effects of such therapy.

• Less than 4 weeks after surgical resection of the brain tumor or less than 2 weeks after stereotactic biopsy before enrollment unless the patient has recovered from acute side effects of such procedures except for neurological effects.

• Plans to receive surgery, radiation therapy or other elective surgeries during the course of the study.

• Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive cardiac failure, myocardial infarction within 6 months before enrollment) that could compromise participation in the study.

• Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except: Use of low dose coumadin-type anticoagulants (≤ 2 mg PO QD) low molecular weight heparins (LMWH), e.g. Enoxaparin sodium (Lovenox) and unfractionated heparin for prophylaxis against central venous catheter thrombosis is allowed.

• Grade 2 or greater peripheral edema or effusion (pleural, pericardial, or ascites).

• Inability to comply with study and/or follow-up procedure.

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.

Avastin-Specific Exclusion Criteria

Subjects meeting any of the following criteria are ineligible for study entry:

• Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg)

• Prior history of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• History of myocardial infarction or unstable angina within 6 months prior to Day 1, the day protocol therapy starts.

• History of stroke or transient ischemic attack within 6 months prior to Day 1

• Significant vascular disease (e.g. aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) (within 6 months prior to Day 1).

• History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 28 days prior to Day 1

• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1

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

• Proteinuria as defined by ≥ +1 on urinalysis dipstick

• Known hypersensitivity to any component of Avastin

• Pregnant (positive pregnancy test) or lactation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Preston Robert Tisch Brain Tumor Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Katy Peters
• Amgen

Investigators

• Principal Investigator: Katherine B Peters, MD, PhD, Duke University
• Principal Investigator: Mary Lou Affronti, DNP ANP MHSc, Duke University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The Preston Robert Tisch Brain Tumor Center

Publications

None provided.

• Responsible Party: Katy Peters, Assistant Professor of Medicine, Duke University
• ClinicalTrials.gov Identifier: NCT01113398
• Other Study ID Numbers: Pro00022491
• First Posted: Apr 29, 2010
• Last Update Posted: Dec 10, 2015
• Last Verified: Dec 1, 2015

• Keywords provided by Katy Peters, Assistant Professor of Medicine, Duke University: glioblastoma multiforme; gliosarcoma; malignant glioma; glioma; Avastin; bevacizumab; AMG 102; rilotumumab; recurrent; Duke; Pro00022491
• Additional relevant MeSH terms: Glioblastoma; Glioma; Gliosarcoma; Bevacizumab; Rilotumumab

Study Results

Participant Flow

Arm/Group Title	AMG 102 With Avastin
Arm/Group Description	Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks. AMG 102: AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes. Avastin: Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.
Period Title: Overall Study
STARTED	36
COMPLETED	36
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	AMG 102 With Avastin
Arm/Group Description	Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks. AMG 102: AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes. Avastin: Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.6 (11.1)
Sex: Female, Male (Count of Participants)
Female	14 38.9%
Male	22 61.1%

Outcome Measures

1. Primary Outcome

Title	Radiographic Response
Description	The percentage of participants with a complete or partial response as determined by modified Response Assessment in Neuro-Oncology (RANO) criteria will be determined. Complete Response (CR) is defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) is defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Tumor assessments are done at baseline and the end of every 6-week cycle thereafter.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	AMG 102 With Avastin
Arm/Group Description	Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks. AMG 102: AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes. Avastin: Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants]	27.8 77.2%

2. Secondary Outcome

Title	Median Overall Survival (OS)
Description	Overall survival is defined as the time in months from the start of protocol treatment until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	AMG 102 With Avastin
Arm/Group Description	Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks. AMG 102: AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes. Avastin: Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.
Measure Participants	36
Median (95% Confidence Interval) [Months]	11.2

3. Secondary Outcome

Title	Six-month Progression-free Survival (PFS6)
Description	The percentage of participants alive and progression-free at 6 months after the start of study treatment will be determined. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	AMG 102 With Avastin
Arm/Group Description	Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks. AMG 102: AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes. Avastin: Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants]	41.7 115.8%

4. Secondary Outcome

Title	Percentage of Participants Who Experience Treatment-related Grade 2 or Greater CNS Hemorrhage or Grade 4 or Greater Non-hematologic Toxicities
Description	The percentage of participants who experience unacceptable toxicity, defined as any treatment-related grade 2 or greater CNS hemorrhage or grade 4 or greater non-hematologic toxicity, will be calculated.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	AMG 102 With Avastin
Arm/Group Description	Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks. AMG 102: AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes. Avastin: Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.
Measure Participants	36
Number [percentage of participants]	5.5 15.3%

Adverse Events

Time Frame	From the start of study treatment for a patient until 30 days after treatment is discontinued.
Adverse Event Reporting Description	Patients will be evaluated for adverse events (AEs) (all grades), serious AEs, and AEs requiring study drug interruption or discontinuation at each study visit for the duration of their participation in the study. The AEs for this study were collected using CTCAE v.3.0, and have been converted to CTCAE v. 4.0 for entry into ClinicalTrials.gov.
Arm/Group Title	AMG 102 With Avastin
Arm/Group Description	Avastin will be administered as a continuous intravenous infusion at 10 mg/kg prior to AMG 102, which will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg. Subjects will receive infusions every 2 weeks. AMG 102: AMG 102 will be administered as a continuous intravenous infusion by an infusion pump at 20 mg/kg every 2 weeks over 60 or 30 minutes. Avastin: Avastin will be administered as a continuous intravenous infusion at 10 mg/kg every 2 weeks (6-week study cycle) over 60 or 30 minutes. Avastin will be given prior to AMG 102.
All Cause Mortality
	AMG 102 With Avastin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	AMG 102 With Avastin
	Affected / at Risk (%)	# Events
Total	6/36 (16.7%)
General disorders
Death NOS	1/36 (2.8%)
Injury, poisoning and procedural complications
Fracture	1/36 (2.8%)
Investigations
Electrocardiogram QT corrected interval prolonged	1/36 (2.8%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify	1/36 (2.8%)
Nervous system disorders
Seizure	1/36 (2.8%)
Vascular disorders
Hypotension	1/36 (2.8%)
Thromboembolic event	4/36 (11.1%)
Other (Not Including Serious) Adverse Events
	AMG 102 With Avastin
	Affected / at Risk (%)	# Events
Total	36/36 (100%)
Blood and lymphatic system disorders
Anemia	6/36 (16.7%)
Blood and lymphatic system disorders - Other, specify	1/36 (2.8%)
Cardiac disorders
Palpitations	2/36 (5.6%)
Ventricular arrhythmia	1/36 (2.8%)
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify	3/36 (8.3%)
Hearing impaired	1/36 (2.8%)
Eye disorders
Blurred vision	2/36 (5.6%)
Extraocular muscle paresis	4/36 (11.1%)
Eye disorders - Other, specify	3/36 (8.3%)
Photophobia	1/36 (2.8%)
Gastrointestinal disorders
Abdominal distension	1/36 (2.8%)
Abdominal pain	1/36 (2.8%)
Anal hemorrhage	5/36 (13.9%)
Anal mucositis	1/36 (2.8%)
Anal pain	1/36 (2.8%)
Constipation	7/36 (19.4%)
Diarrhea	9/36 (25%)
Dry mouth	3/36 (8.3%)
Fecal incontinence	1/36 (2.8%)
Gastritis	3/36 (8.3%)
Gastrointestinal disorders - Other, specify	2/36 (5.6%)
Gingival pain	1/36 (2.8%)
Hemorrhoids	1/36 (2.8%)
Lip pain	1/36 (2.8%)
Nausea	9/36 (25%)
Oral hemorrhage	1/36 (2.8%)
Periodontal disease	1/36 (2.8%)
Rectal hemorrhage	1/36 (2.8%)
Toothache	1/36 (2.8%)
Vomiting	6/36 (16.7%)
General disorders
Chills	2/36 (5.6%)
Edema face	2/36 (5.6%)
Edema limbs	11/36 (30.6%)
Edema trunk	2/36 (5.6%)
Fatigue	26/36 (72.2%)
Fever	1/36 (2.8%)
Gait disturbance	5/36 (13.9%)
General disorders and administration site conditions - Other, specify	2/36 (5.6%)
Injection site reaction	1/36 (2.8%)
Pain	8/36 (22.2%)
Infections and infestations
Bronchial infection	1/36 (2.8%)
Gum infection	1/36 (2.8%)
Infections and infestations - Other, specify	5/36 (13.9%)
Lung infection	2/36 (5.6%)
Mucosal infection	1/36 (2.8%)
Sinusitis	1/36 (2.8%)
Skin infection	1/36 (2.8%)
Upper respiratory infection	3/36 (8.3%)
Urinary tract infection	3/36 (8.3%)
Wound infection	1/36 (2.8%)
Injury, poisoning and procedural complications
Bruising	2/36 (5.6%)
Burn	1/36 (2.8%)
Fracture	2/36 (5.6%)
Radiation recall reaction (dermatologic)	1/36 (2.8%)
Wound dehiscence	3/36 (8.3%)
Investigations
Alanine aminotransferase increased	9/36 (25%)
Alkaline phosphatase increased	10/36 (27.8%)
Aspartate aminotransferase increased	6/36 (16.7%)
Blood bilirubin increased	3/36 (8.3%)
Creatinine increased	2/36 (5.6%)
Electrocardiogram QT corrected interval prolonged	3/36 (8.3%)
Neutrophil count decreased	1/36 (2.8%)
Platelet count decreased	13/36 (36.1%)
Weight gain	13/36 (36.1%)
Weight loss	3/36 (8.3%)
White blood cell decreased	1/36 (2.8%)
Metabolism and nutrition disorders
Anorexia	2/36 (5.6%)
Dehydration	1/36 (2.8%)
Hyperglycemia	16/36 (44.4%)
Hyperkalemia	1/36 (2.8%)
Hypernatremia	1/36 (2.8%)
Hypoalbuminemia	18/36 (50%)
Hypocalcemia	19/36 (52.8%)
Hypoglycemia	2/36 (5.6%)
Hypokalemia	8/36 (22.2%)
Hypomagnesemia	2/36 (5.6%)
Hyponatremia	2/36 (5.6%)
Hypophosphatemia	1/36 (2.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/36 (22.2%)
Back pain	3/36 (8.3%)
Chest wall pain	5/36 (13.9%)
Muscle weakness left-sided	1/36 (2.8%)
Muscle weakness lower limb	2/36 (5.6%)
Musculoskeletal and connective tissue disorder - Other, specify	4/36 (11.1%)
Myalgia	5/36 (13.9%)
Pain in extremity	2/36 (5.6%)
Nervous system disorders
Acoustic nerve disorder NOS	1/36 (2.8%)
Ataxia	4/36 (11.1%)
Cognitive disturbance	3/36 (8.3%)
Dizziness	3/36 (8.3%)
Dysgeusia	2/36 (5.6%)
Dysphasia	9/36 (25%)
Headache	13/36 (36.1%)
Intracranial hemorrhage	1/36 (2.8%)
Memory impairment	6/36 (16.7%)
Nervous system disorders - Other, specify	4/36 (11.1%)
Peripheral sensory neuropathy	5/36 (13.9%)
Seizure	12/36 (33.3%)
Tremor	1/36 (2.8%)
Psychiatric disorders
Agitation	2/36 (5.6%)
Anxiety	5/36 (13.9%)
Confusion	7/36 (19.4%)
Depression	4/36 (11.1%)
Insomnia	10/36 (27.8%)
Renal and urinary disorders
Proteinuria	4/36 (11.1%)
Urinary frequency	5/36 (13.9%)
Urinary incontinence	4/36 (11.1%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	14/36 (38.9%)
Bronchospasm	1/36 (2.8%)
Cough	10/36 (27.8%)
Dyspnea	8/36 (22.2%)
Epistaxis	4/36 (11.1%)
Hypoxia	1/36 (2.8%)
Pharyngolaryngeal pain	1/36 (2.8%)
Sinus disorder	3/36 (8.3%)
Voice alteration	14/36 (38.9%)
Skin and subcutaneous tissue disorders
Dry skin	1/36 (2.8%)
Erythema multiforme	1/36 (2.8%)
Hyperhidrosis	1/36 (2.8%)
Nail loss	1/36 (2.8%)
Pruritus	3/36 (8.3%)
Purpura	2/36 (5.6%)
Rash acneiform	6/36 (16.7%)
Rash maculo-papular	2/36 (5.6%)
Scalp pain	1/36 (2.8%)
Skin and subcutaneous tissue disorders - Other, specify	7/36 (19.4%)
Skin induration	1/36 (2.8%)
Vascular disorders
Flushing	2/36 (5.6%)
Hypertension	8/36 (22.2%)
Hypotension	1/36 (2.8%)
Thromboembolic event	1/36 (2.8%)
Vascular disorders - Other, specify	2/36 (5.6%)

Limitations/Caveats

11/21/14 Amgen notified PI they stopped their own AMG102 studies due to increased risk found in the TX arm on a different study. Dr. Peters decided to stop TX on the 3 current subjects on her study at that time although no increased risks were found.

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.