Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors

NCT00876993 | Completed Phase 1 Results DMC

• 1 other identifier: ACH-CNS-001
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.

Conditions

Central Nervous System Tumors

Outcome Measures

Primary Outcomes (1)

• Measurement of Number of Adverse Events

  Collect and grade the all of the adverse events to evaluate for safety. This data was collected for the first 2 cycles for each participant.

  Two 28-day cycles

Secondary Outcomes (3)

• Best Response of Children With Recurrent or Refractory Central Nervous System Tumors With This Combination of Chemotherapy Agents.

  Every 2 cycles up to 24 cycles

• 2 Year Event Free Survival With Children Treated With This Regimen.

  2 year

• To Provide Safety and Efficacy Data for to Recommend Further Larger Studies.

  Two 28 day cycles

Study Arms (5)

Dose Level 0

EXPERIMENTAL

Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m\^2 IV Temozolomide 75 mg/m\^2 PO

Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide

Dose Level 1

EXPERIMENTAL

Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m\^2 IV Temozolomide 125 mg/m\^2 PO

Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide

Dose Level 2

EXPERIMENTAL

Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m\^2 IV Temozolomide 175 mg/m\^2 PO

Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide

Dose Level 3

EXPERIMENTAL

Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m\^2 IV Temozolomide 200 mg/m\^2 PO

Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide

Dose Level 4

EXPERIMENTAL

Bevacizmuab 10 mg/kg IV Irinotecan 150 mg/m\^2 IV Temozolomide 200 mg/m\^2 PO

Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide

Interventions

Bevacizumab DRUG

Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle

Also known as: Irinotecan and temozolomide

Dose Level 0; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Irinotecan DRUG

Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.

Also known as: Bevacizumab and temozolomide

Dose Level 0; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Temozolomide DRUG

For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course. Doses will be escalated according to standard phase I dose escalation criteria. Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)

Also known as: Bevacizumab and irinotecan

Dose Level 0; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Eligibility Criteria

• Age: 18 Months - 23 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Medulloblastomas, high-grade glioma, low-grade glioma, and ependymoma are eligible. Other central nervous system tumors may be considered for treatment at discretion of investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic pathway tumor.
• The patient should have failed first line therapy and be considered refractory, relapsed, or recurrent. Exceptions are high grade gliomas including brain stem gliomas.
• Age 18 months though age 23 years are eligible for this protocol.
• The patient may have received any of the agents, but not in this combination. Patients will not be eligible if they have received the combination of bevacizumab and IV irinotecan as prior therapy. They will not be eligible if they had progressive disease on any of these agents. Investigator discretion may also be used.
• Bone marrow should be recovered from prior therapy with ANC \>1500 and platelets \>100,000.
• Serum creatinine should be less than institutional upper limit of norm.
• ALT/AST \<3 times normal and bilirubin \<1.5 times normal.
• Neurologic symptoms should be stable for 1 week with stable or decreasing doses of steroids.
• Patients should not be pregnant or breast feeding.

You may not qualify if:

• Patients with bleeding disorders or on anticoagulants.
• Uncontrolled hypertension.
• Other risks of bleeding determined on individual basis.
• Patients receiving enzyme inducing anticonvulsants.
• Patients with significant cardiac or pulmonary dysfunction that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results.
• For patients receiving bevacizumab, those who have had surgical procedures should not receive bevacizumab within 28 days of a major procedure, 14 days of an intermediate procedure and 7 days of a minor procedure. Lumbar punctures or placement of PICC lines are not considered minor procedures and may occur at any time prior to or during therapy.

Sponsors & Collaborators

• Johns Hopkins All Children's Hospital: lead
• The V Foundation: collaborator
• Brain Tumor Alliance: collaborator

Study Sites (1)

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Related Publications (1)

• Metts J, Harrington B, Salman E, Bradfield SM, Flanary J, Mosha M, Amankwah E, Stapleton S. A phase I study of irinotecan and temozolomide with bevacizumab in children with recurrent/refractory central nervous system tumors. Childs Nerv Syst. 2022 May;38(5):919-928. doi: 10.1007/s00381-022-05479-7. Epub 2022 Mar 8.

  PMID: 35260913 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

Bevacizumab; Irinotecan; Temozolomide

Condition Hierarchy (Ancestors)

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; Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Stacie Stapleton
• Organization: Johns Hopkins All Children's Hospital

stacie.stapleton@jhmi.edu

727-767-4176

Study Officials

• Stacie Stapleton, MD

  Johns Hopkins All Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2009
• First Posted: April 7, 2009
• Study Start: September 1, 2008
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: July 3, 2023
• Results First Posted: August 8, 2019

Record last verified: 2023-06

Locations

US (1)