Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors



Status:Recruiting
Conditions:Brain Cancer, Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:2 - 21
Updated:3/16/2019
Start Date:November 16, 2017
End Date:May 31, 2022
Contact:Eisai Medical Information
Email:esi_oncmedinfo@eisai.com
Phone:1-888-274-2378

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A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including CNS Tumors

Phase 1 of this study, utilizing a rolling 6 design, will be conducted to determine a maximum
tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to describe the toxicities of
lenvatinib administered in combination with everolimus once daily to pediatric participants
with recurrent/refractory solid tumors. Phase 2, utilizing Simon's optimal 2-stage design,
will be conducted to estimate the antitumor activity of lenvatinib in combination with
everolimus in pediatric participants with selected recurrent/refractory solid tumors
including Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET), rhabdomyosarcoma,
and high grade glioma (HGG) using objective response rate (ORR) at Week 16 as the outcome
measure.


Inclusion Criteria

- ≥2 years and <18 years of age for enrolment in Phase 1 or ≥2 years and ≤21 years of
age for enrolment in Phase 2.

- Recurrent or refractory solid tumors

- Phase 1: All solid tumors (measurable or evaluable disease), including primary
central nervous system (CNS) tumors; exclusion of hepatoblastoma and lymphomas.
Participants with diffuse intrinsic pontine glioma, optic pathway glioma, or
pineal tumors with elevated tumor markers (alpha-fetoprotein [AFP] and beta-human
chorionic gonadotropin [ß-hCG][or human chorionic gonadotropin [hCG])do not
require histological or cytological confirmation of diagnosis

- Phase 2: Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET),
Rhabdomyosarcoma, High Grade Glioma (HGG) (all must have measurable disease);
exclusion of Diffuse Intrinsic Pontine Glioma

- Histologically or cytologically confirmed diagnosis

- Measurable disease that meets the following criteria (Phase 2):

1. RECIST 1.1 (for all tumor types except HGG): At least 1 lesion of ≥1.0 cm in the
longest diameter for a non lymph node or ≥1.5 cm in the short-axis diameter for a
lymph node which is serially measurable according to RECIST 1.1 using computed
tomography /magnetic resonance imaging (CT/MRI)

2. Response Assessment in Neuro-Oncology (RANO) for high grade glioma (HGG): At
least one lesion must be measurable as defined as a bi dimensionally contrast
enhancing lesion with clearly defined margins by CT or MRI scan, with a minimal
diameter of 1 cm, and visible on 2 axial slices which are preferably at most 5 mm
apart with 0 mm skip

Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as
radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1
to be deemed a target lesion

- Karnofsky performance score ≥50 for participants>16 year of age and Lansky play score
≥50 for participants ≤16 years of age. Neurologic deficits in participants with CNS
tumors must have been relatively stable for at least 7 days prior to study enrollment.
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

- Prior Therapy

- Participants must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy

- Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: ≥21
days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days
if prior nitrosourea)

- Anti-cancer agents not known to be myelosuppressive (eg, not associated with
reduced platelet or absolute neutrophil counts): ≥7 days after the last dose of
agent

- Monoclonal antibodies: ≥21 days or 3 half-lives (whichever is shorter) of the
antibody must have elapsed after the last dose of a monoclonal antibody
(including checkpoint inhibitors). Toxicity related to prior antibody therapy
must be recovered to Grade ≤1

- Corticosteroids: If used to modify immune adverse events related to prior
therapy, ≥14 days must have elapsed since last dose of corticosteroid.
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

- Hematopoietic growth factors: ≥14 days after the last dose of a long-acting
growth factor 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

- Interleukins, interferons, and cytokines (other than hematopoietic growth
factors): ≥21 days after the completion of interleukins, interferons or cytokines
(other than hematopoietic growth factors)

- Stem cell infusions (with or without total body irradiation): Allogeneic
(non-autologous) bone marrow or stem cell transplant, or any stem cell infusion
including donor leukocytes infusion or boost infusion: ≥84 days after infusion
and no evidence of graft versus host disease; Autologous stem cell infusion
including boost infusion: ≥42 days

- Cellular Therapy: ≥42 days after the completion of any type of cellular therapy
(eg, modified T cells, natural killer cells, dendritic cells, etc)

- Radiotherapy (XRT)/External Beam Irradiation including Protons: ≥14 days after
local XRT; ≥150 days after total body irradiation, craniospinal XRT or if
radiation to ≥50% of the pelvis; ≥42 days if other substantial bone marrow
radiation.

- Radiopharmaceutical therapy: ≥42 days after systemically administered therapy.

- Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted or
mammalian target of rapamycin (mTOR)-targeted therapies: Must not have received
prior exposure to lenvatinib; May have previously progressed on an mTOR
inhibitor; No more than 2 prior VEGF/VEGFR-targeted therapies (For Phase 2 only);
Must not have received prior VEGF/VEGFR-targeted therapy in combination with an
mTOR inhibitor (For Phase 2 only)

- Adequate bone marrow function for participants with solid tumors without known bone
marrow involvement

- Adequate bone marrow function for participants with known bone marrow metastatic
disease

- Adequate renal function

- Adequate liver function

- Adequate cardiac function

- Adequate neurologic function

- Adequate blood pressure (BP) control with or without antihypertensive medications

- Adequate coagulation

- Adequate pancreatic function

- Participants must have a minimum body surface area (BSA) of 0.6 m^2 at study entry.

Exclusion Criteria

- Participants who have had or are planning to have the following invasive procedures

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

- Central line placement or subcutaneous port placement is not considered major
surgery. External central lines must be placed at least 3 days prior to
enrollment and subcutaneous ports must be placed at least 7 days prior to
enrollment

- Fine needle aspirate within 7 days prior to enrolment

- Surgical or other wounds must be adequately healed prior to enrolment

- 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 who have non-healing wound, unhealed or incompletely healed fracture, or
a compound (open) bone fracture at the time of enrolment

- Clinical evidence of nephrotic syndrome prior to enrolment

- Gastrointestinal bleeding or active hemoptysis (bright red blood of at least half
teaspoon) within 21 days prior to enrolment

- Thrombotic/ thromboembolic event requiring systemic anticoagulation within 90 days
prior to enrollment

- Evidence of new intracranial hemorrhage of more than punctate size on MRI assessment
obtained within 28 days prior to study enrollment for Participants with HGG

- Diagnosis of lymphoma

- Radiographic evidence of major blood vessel invasion/infiltration.

- Evidence of untreated CNS metastases

- Participants who are currently receiving enzyme-inducing anticonvulsants

- Participants chronically receiving strong cytochrome P450 3A4 (CYP3A4)/P-glycoprotein
(P-gp) inhibitors or inducers within 7 days prior to study enrollment

- Females who are breastfeeding or pregnant. For females of childbearing potential, a
negative screening pregnancy test must be obtained within 72 hours before the first
dose of study drug
We found this trial at
20
sites
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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Ann Arbor, MI 48109Bus: -
Ann Arbor, Michigan 48109
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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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4650 Sunset Blvd
Los Angeles, California 90027
 (323) 660-2450
Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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Los Angeles, 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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13123 E 16th Ave
Aurora, Colorado 80045
(720) 777-1234
Children's Hospital Colorado At Children's Hospital Colorado, we see more, treat more and heal more...
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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225 E Chicago Ave
Chicago, Illinois 60611
(312) 227-4000
Ann & Robert H. Lurie Children's Hospital of Chicago Ann & Robert H. Lurie Children
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1935 Medical District Dr
Dallas, Texas 75235
(214) 456-7000
Children's Medical Center of Dallas Children's Medical Center is private, not-for-profit, and is the fifth-largest...
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6621 Fannin St
Houston, Texas 77030
(832) 824-1000
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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Indianapolis, IN
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11234 Anderson St
Loma Linda, California 92354
(909) 558-4000
Loma Linda University Medical Center An outgrowth of the original Sanitarium on the hill in...
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Minneapolis, Minnesota 55455
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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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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