Clinical Trials /

CED With Irinotecan Liposome Injection Using Real Time Imaging in Children With Diffuse Intrinsic Pontine Glioma (DIPG) (PNOC 009)

NCT03086616

Description:

This is a Phase I and Early Efficacy Study of Convection Enhanced Delivery (CED) of irinotecan liposome injection (nal-IRI) Using Real Time Imaging with Gadolinium in Children with Diffuse Intrinsic Pontine Glioma who have completed focal radiotherapy

Related Conditions:
  • Diffuse Intrinsic Pontine Glioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CED With Irinotecan Liposome Injection Using Real Time Imaging in Children With DIPG
  • Official Title: A Phase I and Early Efficacy Study of Convection Enhanced Delivery of Irinotecan Liposome Injection Using Real Time Imaging With Gadolinium in Children With Diffuse Intrinsic Pontine Glioma

Clinical Trial IDs

  • ORG STUDY ID: PNOC 009
  • SECONDARY ID: 160816
  • NCT ID: NCT03086616

Conditions

  • Diffuse Intrinsic Pontine Glioma

Interventions

DrugSynonymsArms
Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)Irinotecan Liposome InjectionNewly Diagnosed DIPG

Purpose

This is a Phase I and Early Efficacy Study of Convection Enhanced Delivery (CED) of irinotecan liposome injection (nal-IRI) Using Real Time Imaging with Gadolinium in Children with Diffuse Intrinsic Pontine Glioma who have completed focal radiotherapy

Detailed Description

      This study will assess the safety and tolerability of repeated administration of nal-IRI
      co-infused with gadoteridol given by intratumoral CED in children with newly diagnosed DIPG.
    

Trial Arms

NameTypeDescriptionInterventions
Newly Diagnosed DIPGExperimentalConvection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI): Nal-IRI given directly into the tumor using a method called CED to newly diagnosed DIPG subjects after completion of radiotherapy. CED will be performed every 4-6 weeks. Drug concentration will start at 20mg/ml and escalate up to 40 mg/ml concentration.
  • Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with newly diagnosed DIPG who have completed focal radiotherapy are
             eligible. Patients with disseminated disease are not eligible, and MRI of the spine
             must be performed if disseminated disease is suspected by the treating physician.

          -  Treatment must begin at a minimum of 28 days after but no later than 42 days of the
             date of the completion of radiotherapy.

          -  Prior Chemotherapy: No prior experimental chemotherapy is allowed. If a subject
             received chemotherapy during radiation, the subject needs to be discussed with the
             study chair(s). The use of temolzolomide is allowed at standard pediatric dosing
             during radiation therapy. All other therapies need to be discussed with the study
             chair.

          -  Prior Radiation: Patients must have received prior treatment with focal radiotherapy
             as part of initial treatment for DIPG and had their last dose at least 28 days prior
             to and no later than 42 days from the first CED treatment with liposomal-irinotecan.

          -  Age ≥ 3 and < 39 years of age.

          -  Karnofsky ≥ 50 for patients > 16 years of age and Lansky ≥ 50 for patients 16 years
             of age and younger. 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.

          -  Corticosteroids: Patients who are receiving dexamethasone must be on a stable or
             decreasing dose for at least 1 week prior to registration.

          -  Organ Function Requirements

               -  Adequate Bone Marrow Function Defined as:Peripheral absolute neutrophil count
                  (ANC) ≥1000/mm3 and platelet count ≥ 100,000/mm3 (transfusion independent,
                  defined as not receiving platelet transfusions for at least 7 days prior to
                  enrollment) and normal coagulation defined as normal INR or per institutional
                  guidelines.

               -  Adequate Renal Function Defined as:

                    -  Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 or

                    -  A serum creatinine based on age/gender as follows:

        Age Maximum Serum Creatinine (mg/dL) Male Female 3 to < 6 years 0.8 0.8 6 to < 10 years 1
        1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

        ≥ 16 years 1.7 1.4

          -  Adequate Liver Function Defined as: Bilirubin (sum of conjugated + unconjugated) less
             than or equal to 1.5 x upper limit of normal (ULN) for age and SGPT (ALT) less than
             or equal to 110 U/L. and Serum albumin ≥ 2 g/dL.

          -  Adequate Neurologic Function Defined as: 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.

               -  Ability to understand and the willingness to sign a written informed consent
                  document.

        Exclusion Criteria:

          -  Patients who have had prior experimental chemotherapy.

          -  Patients who are receiving any other investigational agents.

          -  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 7 days of registration.

          -  Patients with inability to return for follow-up visits or obtain follow-up studies
             required to assess toxicity to therapy.

          -  Patients with MRI or clinical evidence of uncontrolled tumor mass effect are
             excluded; the assessment of mass effect should be made by the study chair and study
             neurosurgeon prior to any planned CED treatment.

          -  Leptomeningeal or subarachnoid disseminated disease.

          -  Patients with evidence of hemorrhage (besides what is expected if a patient underwent
             a biopsy). These subjects should be discussed with the study chair.

          -  Patients with evidence of cystic changes greater than 1 cm in diameter will be
             excluded. These subjects should be discussed with the study chair.

          -  Patients must not be on enzyme-inducing anticonvulsants or other drugs that might
             interact with the cytochrome P450 enzyme system. If previously on an EIAED, patient
             must be off for at least 10 days prior to CED infusion.
      
Maximum Eligible Age:39 Years
Minimum Eligible Age:3 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events related to treatment
Time Frame:12 months
Safety Issue:
Description:Safety of repeated CED of nal-IRI following standard of care focal radiotherapy will be assessed by monitoring for adverse events, scheduled laboratory assessments, vital sign measurements, and physical examinations for subjects who receive the vaccination. The severity of toxicities will be graded according to the NCI CTCAE v4.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to study drug(s). Grade 1 and 2 adverse events will be summarized if related to study therapy.

Secondary Outcome Measures

Measure:Overall Survival (OS) at 12 months (OS12)
Time Frame:12 months
Safety Issue:
Description:Any eligible subject treated on the dose level that will be investigated within the expansion cohort will be considered evaluable for clinical efficacy. Analyses will be performed after all enrolled patients have completed 12 months, or whenever the status of all patients has been established, whichever comes first.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of California, San Francisco

Trial Keywords

  • DIPG
  • CED
  • glioma

Last Updated

March 16, 2017