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Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors
Overall Recruitment Status: Active, currently enrolling
 
Official Title
A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including CNS Tumors
 
Region Sponsors
California - Northern
Children's Oncology Group
 
Acronym KP IRB No.
1483749
 
Study Type Phase
Clinical Trial Phase II
 
Study Population Description
Individuals with Recurrent and Refractory Solid Tumors
 
Purpose
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.
 
Detailed Description
Maximum tolerated dose (MTD) of lenvatinib in combination with everolimus. Time Frame: Cycle 1 (Day 1 to Day 28) of the Treatment Phase. The sponsor and Protocol Steering Committee will review all participants' safety and clinical data to determine the MTD of the combination of lenvatinib with everolimus. If 2 or more of a cohort of up to 6 participants experience dose-limiting toxicities (DLTs: side effects that prevent a dose increase) at a given dose level, then the MTD has been exceeded and dose escalation will be stopped. Recommended Phase 2 dose (RP2D) of lenvatinib in combination with everolimus. Time Frame: Cycle 1 (Day 1 to Day 28) of the Treatment Phase. The sponsor and Protocol Steering Committee will review all participants' safety and clinical data to determine the MTD of the combination of lenvatinib with everolimus. If 2 or more of a cohort of up to 6 participants experience DLTs (side effects that prevent a dose increase) at a given dose level, then the MTD has been exceeded and dose escalation will be stopped. The RP2D is determined based on the MTD and DLTs.
 
Gender Age Limit
Male & Female 2 - 21 years
 
Inclusion Criteria
  • >/=2 years and /=2 years and
  • 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): # 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), # 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
  • Please contact study team for more eligibility criteria
 
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
  • Please contact study team for more eligibility criteria

 
Keywords and/or Specific Medical Conditions
  • Antineoplastic Agents
  • Neoplasms by Site
  • Central Nervous System Neoplasms
  • Nervous System Diseases
  • Everolimus
  • Nervous System Neoplasms
  • Ewing sarcoma/peripheral primitive neuroectodermal tumor
  • Neurology (Neurological Disorders)
  • high grade glioma
  • rhabdomyosarcoma
  • Immunosuppressive Agents
  • Sirolimus
  • Lenvatinib
  • solid tumors
  • Neoplasms
  • Oncology (Pediatrics)
 
KP Clinical Facility
  • Oakland Medical Center
  • Roseville Medical Center
  • Santa Clara Medical Center-Homestead
 
Clinical Area
  • Neurology (Neurological Disorders)
  • Oncology (Pediatrics)
  • Pediatrics


Principal Investigator:
Laura Campbell, MD
Contact Information:
- Comprehensive Clinical Research Unit KPNC
-510-301-1939
-susan.x.leu@kp.org
-Oakland Medical Center


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