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

NCT00756340 | Completed Phase 1

• 2 other identifiers: RADBEVNCI-2011-01149
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent or Refractory Solid Tumors; CNS Malignancies

Outcome Measures

Primary Outcomes (1)

• To estimate the MTD and describe the 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

  Within 30 days per subject

Study Arms (1)

1

EXPERIMENTAL

* 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

Drug: Bevacizumab; Drug: Everolimus

Interventions

Bevacizumab DRUG

* 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

Also known as: Avastin(R)

1

Everolimus DRUG

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

Also known as: RAD001, Afinitor(R)

1

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis: Solid tumor, including central nervous tumors, that is recurrent or refractory to standard therapy or for which standard therapy is not available. All research participants must have a pathologic diagnosis either from their initial presentation, or at the time of recurrence or progression. The requirement for histologic verification may be waived for patients with brainstem glioma and optic pathway glioma.
• Performance Status: Karnofsky \> 50% for \> 10 years of age; Lansky \> 50% for children \< 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purposes of assessing performance score.
• Neurologic deficits. Patients with CNS tumors must have stable neurological deficits for a minimum of 1 week prior to study entry.
• Life Expectancy: Must be greater than 8 weeks.
• Prior/Concurrent Therapy: Research participants must have recovered from the acute effects of prior treatment and:
• Chemotherapy: Must not have received myelosuppressive chemotherapy within 3 weeks prior to study entry (6 weeks if prior nitrosurea,).
• Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and greater than or equal to 2 months must have elapsed.
• Steroids: Dose should be stable or decreasing for at least one week prior to starting therapy. Corticosteroid therapy is permissible only for the treatment of increased intracranial pressure in patients with malignancies in the CNS or for spinal cord compression. Corticosteroid should be used at the lowest dose to control symptoms and discontinued if possible.
• Must not be receiving tacrolimus or cyclosporine
• Biologic (anti-neoplastic) agent: At least 7 days since the completion of therapy with a biologic agent.
• XRT: Must not have received XRT within 3 months prior to study entry for craniospinal irradiation (\>24 Gy) or total body irradiation or if greater than or equal to 50% radiation of pelvis; \> 8 weeks for local irradiation to primary tumor; \> 2 weeks for focal irradiation for symptomatic metastatic sites.
• Growth factors: Must be off growth factor(s) \> 1 week prior to study entry (GCSF, GM CSF, erythropoietin).
• Age: ≤ 21 years.
• Organ Function: Must have adequate organ function and marrow function as defined by the following parameters:
• Bone marrow: peripheral ANC \> 1,000/µl, hemoglobin \> 8 g/dl (may be transfusion dependent), platelets \> 100,000/µ (transfusion independent). (Patients with bone marrow involvement are eligible provided they meet these criteria).

You may not qualify if:

• Concurrently receiving any other concomitant anticancer or experimental drug therapy.
• Have ≥ Grade 2 uncontrolled hypertension
• History of a stroke, myocardial infarction, or unstable angina in the previous 6 months
• Evidence of a bleeding diathesis or PT INR\>1.5
• Pre-existing Coagulopathy
• Major surgical procedure(s) within previous 4 weeks prior to study enrollment
• Minor surgical procedures within 7 days prior to study enrollment
• History of an abdominal fistula, GI perforation, or intra-abdominal abscess within previous 6 months.
• A serious, non-healing wound, ulcer, or bone fracture
• In patients with CNS tumors or known CNS metastases, evidence of intracranial or intratumoral hemorrhage on baseline MRI obtained within 14 days prior to study registration.
• If there is proteinuria present on dipstick, patients are excluded if they have \>500 mg protein on 24 hour urine collection.
• Require treatment with any of the medications listed in Appendix II (Excluding dexamethasone: Corticosteroid therapy is permissible only for the treatment of increased intracranial pressure in patients with malignancies in the CNS or for spinal cord compression. Corticosteroid should be used at the lowest dose to control symptoms and discontinued if possible).
• Use of H2 antagonists such as ranitidine, cimetidine and proton pump blockers such as omeprazole are permissible only in conjunction with corticosteroids in the setting of increased intracranial pressure or for spinal cord compression, as these drugs interfere with CYP3A4. If patients are given such drugs, they must be taken at least 4 hours after intake of everolimus.
• Have an uncontrolled infection.
• History of infection with the hepatitis B and/or C viruses or positive hepatitis B virus surface antigen and hepatitis C virus antibody.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (1)

• Santana VM, Sahr N, Tatevossian RG, Jia S, Campagne O, Sykes A, Stewart CF, Furman WL, McGregor LM. A phase 1 trial of everolimus and bevacizumab in children with recurrent solid tumors. Cancer. 2020 Apr 15;126(8):1749-1757. doi: 10.1002/cncr.32722. Epub 2020 Jan 22.

  PMID: 31967673 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Recurrence; Central Nervous System Neoplasms

Interventions

Bevacizumab; Everolimus

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Victor Santana, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2008
• First Posted: September 22, 2008
• Study Start: July 1, 2008
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

US (1)