This is a Phase 1 Study of Eribulin Mesylate in Pediatric Participants With Recurrent or Refractory Solid Tumors (Excluding [Central Nervous System] CNS), Including Lymphomas



Status:Completed
Conditions:Cancer, Lymphoma
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any - 17
Updated:1/17/2019
Start Date:July 31, 2014
End Date:January 28, 2016

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A Phase 1 Study of Eribulin Mesylate, a Novel Microtubule Targeting Chemotherapeutic Agent in Children With Refractory or Recurrent Solid Tumors (Excluding CNS), Including Lymphomas

This is a Phase 1 study of eribulin mesylate in pediatric participants with recurrent or
refractory solid tumors (excluding CNS), including lymphomas. Eribulin mesylate will be
administered intravenously, once per day on Days 1 and 8 of a 21-day cycle. This study aims
to determine the maximum tolerated dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of
this regimen in Part A1 (participants greater than or equal to [>=] 12 months and less than
[<] 18 years). Part A2 will enroll infants (greater than [>] 6 months and <12 months) one
dose level behind the dose level at which participants in Part A1 are enrolling, in order to
maximize safety for infant participants. Additionally, this study aims to describe the
toxicities and the pharmacokinetics of eribulin mesylate when administered to children. In a
preliminary manner, the antitumor effect of eribulin mesylate will also be described.


Inclusion Criteria

- Participants must be >=12 months and <18 years of age at the time of study enrollment
(Part A1).

- Participants must be >6 months and <12 months of age at the time of study enrollment
(Part A2). Participants will enroll one dose level behind the dose level at which
participants in Part A1 are enrolling.

- Participants with refractory or recurrent solid tumors or lymphomas, excluding CNS
tumors, are eligible. Participants must have had histologic verification of malignancy
at original diagnosis or relapse. Participants with primary CNS tumors, known CNS
metastases, or a prior history of CNS metastases are not eligible.

- Participants must have either measurable or evaluable disease.

- Participants 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 participants >16 years of age and Lansky >=50 for participants
less than or equal to (<=)16 years of age. Participants 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.

- Participants must have fully recovered from the acute toxic effects of all prior
anticancer chemotherapy.

1. Myelosuppressive chemotherapy: At least 21 days after the last dose of
myelosuppressive chemotherapy (42 days if prior nitrosourea).

2. Hematopoietic growth factors: At least 14 days after the last dose of a
long-acting growth factor (example 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.

3. Biologic (anti-neoplastic agent): At least 14 days after the last dose of a
biologic agent. For agents that have known adverse events occurring beyond 14
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.

4. Immunotherapy: At least 42 days after the completion of any type of
immunotherapy, example tumor vaccines.

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

6. X-ray telescope (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 and/or entire spinal XRT or if >=50% radiation of pelvis; At least
42 days must have elapsed if other substantial bone marrow (BM) radiation.

7. Stem Cell Infusion without TBI: No evidence of active graft versus host disease
and at least 84 days must have elapsed after transplant or stem cell infusion.

- Adequate Bone Marrow Function Defined as:

1. Peripheral absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3).

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

3. Hemoglobin (Hb) at least 8 gram per deciliter (g/dL) at baseline (blood
transfusions are allowed during the screening period to correct Hb values less
than 8 g/dL).

All participants enrolled on the study must be evaluable for hematologic toxicity.

- Adequate Renal Function Defined as:

1. Creatinine clearance or radioisotope glomerular filtration rate (GFR) >=70
milliliter per minute (ml/min) per (/) 1.73 square meter (m^2) or

2. A serum creatinine milligram per deciliter (mg/dL) based on age/gender as
follows:

1. 6 months to <1 year: male, 0.5; female, 0.5

2. 1 to < 2 years: male, 0.6; female, 0.6

3. 2 to < 6 years: male, 0.8; female, 0.8

4. 6 to < 10 years: male, 1; female, 1

5. 10 to < 13 years: male, 1.2; female, 1.2

6. 13 to < 16 years: male, 1.5; female, 1.4

7. >=16 years: male, 1.7; female, 1.4

The threshold creatinine values were derived from the Schwartz formula for
estimating GFR (Schwartz et al., 1985) utilizing child length and stature
data published by the Centers for Disease Control and Prevention (CDC).

- Adequate Liver Function Defined as:

1. Bilirubin (sum of conjugated + unconjugated) <=1.5 * upper limit of normal (ULN)
for age

2. serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase [ALT]) <=110
units per liter (U/L). For the purpose of this study, the ULN for SGPT is 45 U/L.

3. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])
<= 125 U/L. For the purpose of this study, the ULN for SGOT is 50 U/L.

4. Serum albumin >= 2 g/dL

- Adequate Cardiac Function Defined as:

1. Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50%
by gated radionuclide study

2. Corrected QT interval (QTc) <= 480 millisecond (msec) Note: Participants with
Grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have
correctable causes of prolonged QTc addressed if possible (that is, electrolytes,
medications).

- All participants and/or their participants or legally authorized representatives must
sign a written informed consent. Assent, when appropriate, will be obtained according
to institutional guidelines. Participants must be willing to comply with all aspects
of the protocol.

- Participants with known human immunodeficiency virus (HIV) who have CD4+ T cell counts
greater than or equal to 500 cells/m^3 and who do not require antiretroviral therapy
are eligible.

Exclusion Criteria

- Pregnant or breast-feeding women will not be entered on this study due to risks of
fetal and teratogenic adverse events as seen in animal studies. 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 double
barrier contraceptive method for the entire period in which they are receiving
protocol therapy and up to 6 months after treatment.

- Concomitant Medications

- Participants 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.

- Participants who are currently receiving another investigational drug are not
eligible.

- Participants who are currently receiving other anticancer agents are not
eligible.

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

- Participants who are receiving drugs that prolong the QTc are not eligible.

- Participants who have received prior therapy with eribulin mesylate are not eligible.

- Participants with hypersensitivity to excipients of the study drug are not eligible.
The excipients are ethanol, hydrochloric acid, sodium hydroxide and water for
injection.

- Participants who have a prior history of viral hepatitis (B or C) as demonstrated by
positive serology (presence of antigens) or have an uncontrolled infection requiring
treatment are not eligible.

- Participants with greater than Grade 1 peripheral sensory neuropathy or greater than
Grade 1 peripheral motor neuropathy graded according to the Modified ("Balis")
Pediatric Scale of Peripheral Neuropathies are not eligible.

- Cardiac Pathology

- Participants with known congestive heart failure, symptomatic or left ventricle
(LV) ejection fraction 50% or shortening fraction less than 27% are not eligible.

- Participants with congenital long QT syndrome, bradyarrhythmias, or QTc greater
than 480 msec are not eligible.

- CNS Disease

- Participants with primary CNS tumors are not eligible.

- Participants with prior history of or known metastatic CNS disease involvement
are not eligible. (Note: CNS imaging for participants without a known history of
CNS disease is only required if clinically indicated).

- Participants 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
(with example, 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. NOTE: For purposes of
this study, bone marrow aspirate and biopsy are not considered surgical
procedures and therefore are permitted within 14 days prior to start of protocol
therapy.

- Participants with known bone marrow involvement are not eligible.

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

- Participants 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
18
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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Cincinnati, OH
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1200 Moursund Street
Houston, Texas 77030
(713) 798-4951
Baylor College of Medicine Baylor College of Medicine in Houston, the only private medical school...
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Houston, TX
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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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Philadelphia, PA
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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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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
Midwest Children's Cancer Center The Medical College of Wisconsin Cancer Center is dedicated to providing...
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Milwaukee, WI
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Minneapolis, Minnesota 55435
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630 W 168th St
New York, New York
212-305-2862
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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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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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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