Trebananib in Treating Younger Patients With Relapsed or Refractory Solid Tumors, Including Central Nervous System Tumors



Status:Active, not recruiting
Conditions:Cancer, Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:2 - 21
Updated:7/22/2016
Start Date:February 2012

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A Phase 1 Study of AMG 386, an Angiopoietin Neutralizing Peptibody, in Children With Relapsed or Refractory Solid Tumors, Including CNS Tumors

This phase I trial studies the side effects and best dose of trebananib in treating patients
with solid tumors that has returned after a period of improvement or does not respond to
treatment, including central nervous system tumors. Trebananib may stop the growth of tumor
cells by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To estimate the maximum-tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of
trebananib (AMG 386) administered as a weekly intravenous infusion to children with
recurrent or refractory solid tumors.

II. To determine the tolerability of the solid tumor MTD and/or RP2D of AMG 386 in children
with central nervous system (CNS) tumors.

III. To define and describe the toxicities of AMG 386 administered on this schedule.

IV. To characterize the pharmacokinetics and immunogenicity of AMG 386 in children with
refractory cancer.

V. To measure changes in vascular permeability relative to baseline, evaluated by magnetic
resonance imaging (MRI) perfusion, following AMG 386 administration in pediatric patients
with CNS tumors.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of AMG 386 within the confines of a Phase
1 study.

II. To measure biologic markers of angiogenesis with potential for correlation with disease
response.

OUTLINE: This is a dose-escalation study (part 1) followed by a safety and imaging study
(part 2).

Patients receive trebananib intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22.
Treatment repeats every 28 days in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 to
6 months for up to 1 year.

Inclusion Criteria:

- Part 1: Patients must have had histologic verification of non-CNS solid tumor
malignancy at original diagnosis or relapse

- Part 2: Patients must have had histologic verification of CNS malignancy at original
diagnosis or relapse except in patients with intrinsic brain stem tumors, optic
pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid
(CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic
gonadotropin (HCG)

- Patients must have either measurable or evaluable disease

- Patient's current disease state must be one for which there is no known curative
therapy or therapy proven to prolong survival with an acceptable quality of life

- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50% for patients =< 16
years of age; Note: neurologic deficits in patients with CNS tumors (Part 2 of the
study) must have been relatively stable for at least 7 days prior to study
enrollment; patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the
performance score

- Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer chemotherapy

- Myelosuppressive chemotherapy: at least 21 days after the last dose of
myelosuppressive chemotherapy (42 days if prior nitrosourea)

- Hematopoietic growth factors: at least 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
factor; for agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which
adverse events are known to occur; the duration of this interval must be
discussed with the study chair

- Biologic (anti-neoplastic agent): at least 7 days after the last dose of a
biologic agent; for agents that have known adverse events occurring beyond 7
days after administration, this period must be extended beyond the time during
which adverse events are known to occur; the duration of this interval must be
discussed with the study chair

- Immunotherapy: at least 42 days after the completion of any type of
immunotherapy, e.g. tumor vaccines

- Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose
of a monoclonal antibody

- Radiation therapy (XRT): at least 14 days after local palliative XRT (small
port); at least 150 days must have elapsed if prior total-body irradiation
(TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must
have elapsed if other substantial bone marrow (BM) radiation

- Stem cell infusion without TBI: no evidence of active graft vs host disease and
at least 56 days must have elapsed after transplant or stem cell infusion

- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

- Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment

- Patients with known bone marrow metastatic disease will be eligible for study
provided they meet the required blood counts (may receive transfusions provided they
are not known to be refractory to red cell or platelet transfusions)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)

- Urine protein: =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative
protein is < 1,000 mg in a 24-hour urine sample

- Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110
U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

- Serum albumin >= 2 g/dL

- Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by
gated radionuclide study

- No known cardiac disease

- No history of myocardial infarction, severe or unstable angina, peripheral vascular
disease or familial corrected QT (QTc) prolongation

- Patients with seizure disorder may be enrolled if on anticonvulsants and well
controlled

- Nervous system disorders (Common Terminology Criteria for Adverse Events version 4
[CTCAE v 4]) resulting from prior therapy must be =< grade 2

- For Part 2 only: No evidence of new CNS hemorrhage defined as more than punctate size
and/or more than three foci of punctate hemorrhage on baseline magnetic resonance
imaging (MRI) obtained within 14 days prior to study enrollment

- No evidence of active bleeding

- Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.2 x upper limit of
normal (ULN) and an international normalized ratio (INR) =< 1.2

- A blood pressure (BP) =< the 95th percentile for age, height, and gender, and not
receiving medication for treatment of hypertension

- All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines

Exclusion Criteria:

- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests
must be obtained in girls who are post-menarchal; males or females of reproductive
potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of study participation, and for 6 months after
completion of AMG 386 administration

- Patients receiving corticosteroids who have not been on a stable or decreasing dose
of corticosteroid for at least 7 days prior to enrollment are not eligible

- Patients who are currently receiving another investigational drug are not eligible

- Patients who are currently receiving other anticancer agents are not eligible

- Patients who are receiving cyclosporine, tacrolimus, or other agents to prevent
graft-versus-host disease post bone marrow transplant are not eligible for this trial

- Patients who are currently receiving therapeutic anticoagulation with heparin,
low-molecular weight heparin, or Coumadin are not eligible for this trial

- Patients who are currently receiving aspirin, ibuprofen, or other non-steroidal
anti-inflammatory drugs or anti-platelet agents are not eligible

- Patients who are receiving anti-hypertensive medications for control of blood
pressure at the time of enrollment are not eligible for this trial

- Patients who have an uncontrolled infection are not eligible

- Patients who have received a prior solid organ transplantation are not eligible

- Patients who have had or are planning to have the following invasive procedures are
not eligible:

- Major surgical procedure, laparoscopic procedure, open biopsy, or significant
traumatic injury within 28 days prior to enrollment

- Central line placement or subcutaneous port placement is not considered major
surgery but must be placed at least 3 days prior to enrollment for external
lines (e.g., Hickman or Broviac) and at least 7 days prior to enrollment for
subcutaneous port

- Core biopsy within 7 days prior to enrollment

- Fine-needle aspirate within 7 days prior to enrollment

- Patients with evidence of active bleeding: intratumoral hemorrhage by current
imaging, or bleeding diathesis are not eligible

- Patients with a history (within 365 days prior to study enrollment) of
arterial/venous thromboembolic events including transient ischemic attack (TIA) or
cerebrovascular accident (CVA) are not eligible

- Patients with a history of hemoptysis within 42 days prior to study enrollment are
not eligible

- For Part 2: Patients with CNS tumors and evidence of new CNS hemorrhage of more than
punctate size and/or more than three foci of punctate hemorrhage on baseline MRI
obtained within 14 days prior to study enrollment are not eligible; Note:
echocardiogram (ECHO) gradient MRI sequences per institutional guidelines are
required for patients with CNS tumors

- Patients who have a history of serious or non-healing wound, abdominal fistula,
gastrointestinal ulcer or perforation, bone fracture, or intra-abdominal abscess
within 28 days of study enrollment are not eligible

- Patients with known cardiac or peripheral vascular disease are not eligible

- Patients who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study are not eligible
We found this trial at
22
sites
1600 7th Avenue
Birmingham, Alabama 35233
(205) 638-9100
Children's Hospital of Alabama Children
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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262 Danny Thomas Pl
Memphis, Tennessee 38105
(901) 495-3300
St. Jude Children's Research Hospital St. Jude is unlike any other pediatric treatment and research...
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Memphis, TN
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1201 W La Veta Ave
Orange, California 92868
(714) 997-3000
Children's Hospital of Orange County For more than 45 years, CHOC Children’s has been steadfastly...
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Orange, CA
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South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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4401 Penn Avenue
Pittsburgh, Pennsylvania 15224
412-692-5325
Children's Hospital of Pittsburgh of UPMC UPMC is one of the leading nonprofit health systems...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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Portland, OR
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1540 East Hospital Drive
Ann Arbor, Michigan 48109
(877) 475-6688
C S Mott Children's Hospital Behind the doors of C.S. Mott Children's Hospital there exist...
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Atlanta, GA
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Birmingham, AL
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Chicago, Illinois 60614
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Houston, TX
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705 Riley Hospital Dr
Indianapolis, Indiana 46202
(317) 944-5000
Riley Hospital for Children Riley Hospital for Children at IU Health is a place of...
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Milwaukee, Wisconsin 53226
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Minneapolis, Minnesota 55455
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Minneapolis, MN
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New York, NY
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Philadelphia, Pennsylvania 19104
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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San Francisco, California 94143
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4800 Sand Point Way NE
Seattle, Washington 98105
(206) 987-2000
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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555 University Avenue
Toronto, Ontario M5G 1X8
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111 Michigan Ave NW
Washington, District of Columbia
(202) 476-5000
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
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Washington,
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