Intra-arterial Chemotherapy for the Treatment of Progressive Diffuse Intrinsic Pontine Gliomas (DIPG).

The goal of this pilot study is to determine if intra-arterial (IA) chemotherapy is safe in the treatment of progressive diffuse intrinsic pontine gliomas (DIPG). IA administration of the chemotherapeutic agent enhances the regional distribution of the drug, thereby increasing the local delivered dose while minimizing systemic toxicity. It also provides a treatment option for these patients at the time of tumor recurrence.

Study Overview

• Status: Completed
• Conditions: Diffuse Intrinsic Pontine Glioma (DIPG)
• Intervention / Treatment: Drug: Melphalan hydrochloride

Detailed Description

Delivering the chemotherapeutic agent directly to the tumor via the arterial system avoids the complications and adverse events associated with toxicity from systemic chemotherapy.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric patients of all ages with progressive DIPG.
• Consensus following presentation of the case at the multidisciplinary Pediatric Neuro-Oncology conference, which includes participation of neuro-oncology, neurosurgery, radiation oncology, interventional neuroradiology and neurology.

Exclusion Criteria:

• Documented hypercoagulable disorders or vasculopathies

  • INR value more than a Grade 1 toxicity by CTCAE v 4.0 criteria (>1 - 1.5 x ULN; >1 - 1.5 times above baseline if on anticoagulation).
  • APTT value more than a Grade 1 toxicity by CTCAE v 4.0 criteria (>ULN - 1.5 x ULN).
• Platelets less than 50 x 103/mm3
• Absolute neutrophil count less than 500/ mm3
• Pregnancy
• Documented severe allergic reaction to IV iodinated contrast, specifically bronchospasm and anaphylaxis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IA melphalan; IA melphalan is administered via the basilar artery.	Drug: Melphalan hydrochloride; Drug administered intra-arterially (injection in the artery). Standard dose: Cycle 1: 1 mg, intra-arterial (IA) delivery. Cycle 2: 2 mg, intra-arterial (IA) delivery. Duration of treatment: Eight weeks total - two cycles of IA chemotherapy, separated by four weeks.; Other Names: Alkeran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical safety as determined by number of participants with toxicity	Number of participants with grades 3-5 intracranial hemorrhage, grades 3-5 stroke, as defined by the Nervous system disorder CTCAE, and requirement of blood transfusion.	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Efficacy as assessed by progression free survival	Number of months until disease progression.	2 years

Other Outcome Measures

Outcome Measure	Time Frame
Immediate Efficacy as assessed by number of participants with decrease in required steroid dose	60 days
Immediate Efficacy as assessed by number of participants with decrease in tumor size on MRI	60 days
Immediate Efficacy as assessed by number of participants with decrease in the degree of enhancement on MRI	60 days
Immediate Efficacy as assessed by number of participants with improved neurological examination	60 days

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Solving Kids' Cancer
• Investigators: Principal Investigator: Monica Pearl, M.D., Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2013
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): November 26, 2018

Study Registration Dates

• First Submitted: September 10, 2012
• First Submitted That Met QC Criteria: September 14, 2012
• First Posted (Estimate): September 19, 2012

Study Record Updates

• Last Update Posted (Actual): March 28, 2019
• Last Update Submitted That Met QC Criteria: March 26, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: angiography; intra-arterial chemotherapy; diffuse intrinsic pontine glioma (DIPG)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Stem Neoplasms; Infratentorial Neoplasms; Glioma; Diffuse Intrinsic Pontine Glioma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: J11164; NA_00069122 (Other Identifier: JHMIRB)