Neoplasms

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Recurrence

Osteosarcoma

Neuroblastoma

Sarcoma, Ewing

Rhabdomyosarcoma

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Irinotecan

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide

Amanda Knight, RN, BSN

Joseph Pressey, MD

Haley Jones

Alison Patterson

Jonathan Gill, MD

Angie Cervantez

Olivia Tarnowske

Paul Harker-Murray, MD

This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.

Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors

South Plains Oncology Consortium

Nervous System Diseases

Central Nervous System Neoplasms

Anti-Infective Agents

Bevacizumab

Everolimus

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

* Dose Level 0, Bevacizumab IV every 2 weeks 8 mg/kg, Everolimus 4 mg/m\^2
* Dose Level 1 (starting dose), Bevacizumab IV every 2 weeks 10 mg/kg, Everolimus 4 mg/m\^2
* Dose Level 2, Bevacizumab IV every 2 weeks 10 mg/kg, Everolimus 5 mg/m\^2

* Bevacizumab IV every 2 weeks
* Dose Level 0- 8 mg/kg
* Dose Level 1 (starting dose)- 10 mg/kg
* Dose Level 2- 10 mg/kg

* Everolimus
* Dose Level 0- 4 mg/m2
* Dose level 1 (starting dose)- 4 mg/m2
* Dose Level 2- 5 mg/m2

Victor Santana, MD

The main goals of this Phase I study are to learn about the side effects that may occur when everolimus and bevacizumab are given to children and young adults and to find the highest doses of these drugs that can be given together without causing severe side effects. Bevacizumab will be given into the vein (IV) over 30-90 minutes every two weeks and everolimus tablets will be given daily by mouth. A cycle of therapy will be four weeks.

This is a traditional phase I dose finding study to estimate the maximum tolerated dose (MTD) and describe the dose limiting toxicities (DLT) of the combination of bevacizumab, administered every 2 weeks IV and everolimus administered orally daily to children with recurrent or refractory solid tumors including CNS malignancies. Patients will receive bevacizumab every two weeks IV, and everolimus orally daily. Four consecutive weeks will constitute one course and subsequent courses will immediately follow with no break in the administration of either drug. In the absence of disease progression or unacceptable toxicity, treatment can continue for 2 years. The bevacizumab dose will start at 10 mg/kg. Everolimus will start at 4 mg/m2, 80% of the MTD established in our current phase I trial. A traditional 3+3 dose escalation/de-escalation design will be used to determine the joint MTD for these two agents. Doses to be studied are detailed in the table below. Consistent with the traditional design, we will enroll cohorts of 3 patients at each dose level starting with dose level 1 and will escalate to the next higher dose, if none of these 3 experiences a DLT. If one of 3 patients experiences a DLT at a dose level then 3 more patients will be studied at this level. If none of these 3 experiences a DLT then escalation to the next level will occur. Otherwise the current dose will be considered too toxic and de-escalation will occur. Under this setting, MTD will be the dose level at which 0/3 or 1/6 patient would have experienced DLT and the next dose level is determined to be too toxic.

Exploratory objectives:

1. To preliminarily define the antitumor activity of the combination of everolimus and bevacizumab within the confines of a phase I study
2. To assess the incidence of PTEN and PI3Kinase pathway activation in recurrent or refractory solid tumors of childhood
3. To assess everolimus pharmacokinetics in children, including the effect of concomitant drug therapy (e.g., dexamethasone).
4. To explore changes in correlative magnetic resonance imaging in children receiving everolimus and bevacizumab
5. To identify additional genes both within and outside of the mTOR pathway that may act as determinants of response to everolimus
6. To explore the pharmacogenetic polymorphisms responsible for everolimus disposition (e.g., metabolism and elimination)
7. To test the ability of everolimus to inhibit mTOR pathway signaling in patients with recurrent solid tumors including CNS malignancies in peripheral blood mononuclear cells
8. To estimate blood levels of VEGF, BFGF, TSP-1, I-CAM, v-CAM and circulating endothelial cells prior to, during therapy and after therapy

A Trial of Everolimus and Bevacizumab in Children With Recurrent Solid Tumors

A Phase I Trial of RAD001 (Everolimus) and Avastin(R) (Bevacizumab) in Children With Recurrent Solid Tumors

Novartis Pharmaceuticals

St. Jude Children's Research Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors	NCT02013336	Recurrent or Re... Ewing Sarcoma Rhabdomyosarcom... Neuroblastoma Osteosarcoma	MM-398 (Irinote...	12 Months - 20 Years	South Plains Oncology Consortium
A Trial of Everolimus and Bevacizumab in Children With Recurrent Solid Tumors	NCT00756340	Recurrent or Re... CNS Malignancie...	Bevacizumab Everolimus	- 21 Years	St. Jude Children's Research Hospital
A Trial of Everolimus and Bevacizumab in Children With Recurrent Solid Tumors	NCT00756340	Recurrent or Re... CNS Malignancie...	Bevacizumab Everolimus	- 21 Years	St. Jude Children's Research Hospital
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors	NCT02013336	Recurrent or Re... Ewing Sarcoma Rhabdomyosarcom... Neuroblastoma Osteosarcoma	MM-398 (Irinote...	12 Months - 20 Years	South Plains Oncology Consortium
A Trial of Everolimus and Bevacizumab in Children With Recurrent Solid Tumors	NCT00756340	Recurrent or Re... CNS Malignancie...	Bevacizumab Everolimus	- 21 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for recurrent or refractory solid tumors