Methotrexate Infusion Into the Fourth Ventricle in Children With Malignant Fourth Ventricular Brain Tumors: A Pilot Study

NCT01737671 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 2012-0823NCI-2013-00045
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical research study is to learn if it is safe to receive methotrexate through the fourth ventricle of the brain in patients with brain tumors. Methotrexate is designed to block cancer cells from dividing, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

Conditions

Brain Tumor; Malignant Neoplasm of Fourth Ventricle of Brain

Keywords

Brain tumor; Malignant Fourth Ventricular Brain Tumors; Ependymoma involving brain; Ependymoma involving spine; Recurrent ependymoma involving brain and/or spine; Recurrent atypical teratoid/rhabdoid tumor involving brain; Recurrent atypical teratoid/rhabdoid tumor involving spine; AT/RT; Ommaya reservoir catheter; Methotrexate; Medulloblastoma; ATRT; Atypical teratoid rhabdoid tumor; Ependymoma; Pediatric brain tumor; Intraventricular chemotherapy

Outcome Measures

Primary Outcomes (1)

• Neurological Deficits After Administration of Methotrexate into the Fourth Ventricle of the Brain

  New neurological deficit defined as new cranial neuropathy, nystagmus, change in mental status, motor deficit, or cerebellar finding (ataxia, dysmetria, dysdiadochokinesis) that is attributed by treating physicians to intraventricular methotrexate infusions.

  3 months

Study Arms (1)

Methotrexate Infusion

EXPERIMENTAL

3 consecutive cycles of intraventricular methotrexate infusions into implanted fourth ventricle catheter/Ommaya reservoir following surgical catheter placement into fourth ventricle, each cycle is 4 consecutive daily doses of intraventricular methotrexate with minimum 2 weeks between cycles. If any serum methotrexate level is \> 0.3 micromolar, then Leucovorin therapy administered (5 mg/square meter per dose) every 6 hours by vein or mouth.

Procedure: Ommaya Reservoir; Drug: Methotrexate; Drug: Leucovorin

Interventions

Ommaya Reservoir PROCEDURE

Surgical catheter placement into the fourth ventricle of the brain.

Methotrexate Infusion

Methotrexate DRUG

2 mg into fourth ventricle of the brain via the Ommaya Reservoir for 4 days. Each patient will undergo three cycles with at least two weeks between each cycle.

Methotrexate Infusion

Leucovorin DRUG

5 mg/square meter per dose administered every 6 hours by vein or mouth.

Also known as: Citrovorum, Wellcovorin

Methotrexate Infusion

Eligibility Criteria

• Age: Up to 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• There will be a two-step process of eligibility assessment: Step 1: Eligibility for catheter placement and possible surgical removal of tumor. Step 2: Eligibility for methotrexate infusion.
• Step 1 Eligibility (Pre-Operative Eligibility) Includes: Diagnosis and Age - Patients with tumor originally located within the posterior fossa of the brain: \*Patients ≤ age 21 years with recurrent medulloblastoma (PNET) involving the brain and/or spine \*Patients ≤ age 21 years with recurrent ependymoma involving the brain and/or spine \*Patients ≤ age 21 years with recurrent atypical teratoid/rhabdoid tumor (AT/RT) involving the brain and/or spine.
• Step 1 Elig.: Life Expectancy - Patients must have a life expectancy of at least 12 weeks as estimated by the treating oncologist and neurosurgeon to be considered for enrollment.
• Step 1 Elig: Central Nervous System Function - Patients may be enrolled in the study if they have an altered neurological status, such as somnolence, which is attributed to hydrocephalus and/or mass effect from the brain tumor by the treating physicians. However, after tumor resection and placement of the catheter into the fourth ventricle, the protocol will only be continued if the patient has adequate central nervous system function, defined as: patient is not severely somnolent or comatose and has adequate clinical performance status as defined in protocol section 3.2.2.1.
• Step 2 Elig. (MTX Infusion Elig.): Clinical Performance Status - Patients must have a Lansky score of 50 or greater if ≤ 16 years of age and a Karnofsky score of 50 or greater if they are \> 16 years of age to be eligible for enrollment (See Protocol Section 14.1 for Lansky Play-Performance Scale information; See Protocol Section 14.2 for Karnofsky Performance Scale information).
• Step 2 Elig: Pregnancy - Female patients who are post-menarchal must have a negative pregnancy test to be eligible. Pregnant or lactating female patients are ineligible.
• Step 2 Elig: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. a. Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study. b. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with a growth factor. c. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. 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. These patients must be discussed with the study chair on a case by case basis.
• Step 2 Elig: Bone Marrow Function - patients must have adequate bone marrow function, defined as: a. Peripheral absolute neutrophil count (ANC) ≥ 1000/µL b. Platelet count ≥ 30,000/µL (transfusion independent) c. Hemoglobin ≥ 9.0 gm/dL (may receive RBC transfusions) d. Post-op CSF flow study shows re-establishment of CSF flow.
• All patients and/or their parents or legal guardians must sign a written informed consent.

You may not qualify if:

• Patients will be excluded from this study if currently enrolled in another experimental treatment protocol.
• Patients will be excluded from this study if they have any evidence of infection, in any site, at the time of considered enrollment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

Children's Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Brain Neoplasms; Medulloblastoma; Rhabdoid Tumor; Ependymoma

Interventions

Methotrexate; Leucovorin

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes

Study Officials

• Soumen Khatua, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

• David Sandberg, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: November 29, 2012
• Study Start: December 27, 2012
• Primary Completion: January 11, 2018
• Study Completion: January 11, 2018
• Last Updated: January 19, 2018

Record last verified: 2018-01

Locations

US (2)