Liposomal Irinotecan in Treating Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma

Status: Active

Description

This phase I trial studies the side effects and best dose of liposomal irinotecan in treating children with newly diagnosed diffuse intrinsic pontine glioma. Liposomal irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Patients with newly diagnosed DIPG by magnetic resonance imaging (MRI); defined as patients with a pontine location and diffuse involvement of at least 2/3 of the pons are eligible without histologic diagnosis; for lesions with typical imaging features, biopsy is neither encouraged nor required for eligibility; tumors that are biopsied will be eligible if proven to be supportive for the diagnosis of a DIPG; consensus of diagnosis by the study team must be met
  • Treatment must begin at a minimum of 4 weeks after, but no later than 14 weeks after, the date of the completion of focal radiotherapy
  • Patients should be at least 30 days from last chemotherapy dose prior to start of CED infusion, with exception of antibody half-lives; for antibody therapies, at least 3 half-lives of the antibody after last dose of monoclonal antibody should have passed prior to CED infusion; patients less than 30 days from last chemotherapy dose should be discussed with the study chair(s)
  • Patients must have completed prior treatment with standard focal radiotherapy as part of initial treatment for DIPG and had their last dose at least 4 weeks prior to and no later than 14 weeks from the first CED treatment; patients beyond 14 weeks from radiation therapy but with stable disease should be discussed with the study chair
  • Age >= 2 years of age; patients younger than 3 years of age may be enrolled on study at the discretion of the study chair(s) if supporting evidence that brainstem lesion represents a brainstem glioma.
  • Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 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 purpose of assessing the performance score
  • Life expectancy of greater than 12 weeks measured from the date of completion of radiotherapy
  • Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration
  • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 14 days prior to registration)
  • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 14 days prior to registration)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender (within 14 days prior to registration) as follows: * Age 2 to < 6 years; maximum serum creatinine (mg/dL) 0.8 (male and female) * Age 6 to < 10 years; maximum serum creatinine (mg/dL) 1 (male and female) * Age 10 to < 13 years; maximum serum creatinine (mg/dL) 1.2 (male and female) * Age 13 to < 16 years; maximum serum creatinine (mg/dL) 1.5 (male) and 1.4 (female) * Age >= 16 years; maximum serum creatinine (mg/dL) 1.7 (male) and 1.4 (female)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 14 days prior to registration)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (within 14 days of registration)
  • Serum albumin >= 2 g/dL (within 14 days prior to registration)
  • Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled
  • The effects of irinotecan liposome injection on the developing human fetus are unknown; for this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of irinotecan liposome injection administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate

Exclusion Criteria

  • Patients who had clinical and/or radiographic (magnetic resonance imaging [MRI]) progression of tumor following external beam radiation therapy
  • Patients with metastatic disease, including leptomeningeal or subarachnoid disseminated disease
  • Patients with tumor morphology or other imaging findings that predict poor coverage of the majority of the tumor including significant tumor volume outside the pons or presence of large cysts within the tumor that would prevent adequate tumor coverage by CED; patients with concern for adequate tumor coverage based on tumor morphology should be discussed with the study chairs
  • Patients who are receiving any other tumor-directed therapy
  • Patients with MRI or clinical evidence of uncontrolled tumor mass effect are excluded; the patients should be discussed with the study chair(s) and study neurosurgeon prior to any planned CED treatment
  • Untreated symptomatic hydrocephalus determined by treating physician
  • Patients should not be on enzyme-inducing anticonvulsants or other drugs that might interact with the cytochrome P450 enzyme system; if previously on an enzyme-inducing anti-epileptic drug (EIAED), patients should be off for at least 10 days prior to CED infusion and discussed with the study chair
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to irinotecan, topotecan, gadolinium, or lipids
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Female patients of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test within 14 days of registration
  • Patients who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy; telemedicine visits are acceptable

Locations & Contacts

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: Sabine Mueller
Phone: 415-476-3831
Email: Sabine.Mueller@ucsf.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of repeated administration of liposomal irinotecan (liposomal encapsulation of irinotecan [nal-IRI]) co-infused with gadoteridol given by intratumoral convection enhanced delivery in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

SECONDARY OBJECTIVES:

I. To determine the clinical efficacy of repeated administration of nal-IRI given by intratumoral convection enhanced delivery (CED) in children with newly diagnosed DIPG in the confines of a phase I and early efficacy study.

EXPLORATORY OBJECTIVES:

I. To assess the magnetic resonance image-guided intracranial injection procedure in patients with DIPG by correlating the observed distribution of gadoteridol to pre-treatment modeling of the drug distribution utilizing predictive imaging software.

II. To assess Quality of Life (QOL) in pediatric patients with newly diagnosed DIPG treated with nal-IRI co-infused with gadoteridol given by intratumoral CED.

III. Perform central review of imaging to explore magnetic resonance (MR) qualitative and quantitative measures as markers of disease response and/or progression and treatment effect in comparison to institutional evaluation of disease response and/or progression.

OUTLINE: This is a dose-escalation study.

Patients receive liposomal irinotecan intratumorally (IT) via CED every 4-8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
UCSF Medical Center-Mount Zion

Principal Investigator
Sabine Mueller

Trial IDs

Primary ID 160816
Secondary IDs NCI-2017-01829, 17-21535, PNOC009
Clinicaltrials.gov ID NCT03086616