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CED With Irinotecan Liposome Injection Using Real Time Imaging in Children With DIPG

This study is currently recruiting participants.
Verified November 2017 by University of California, San Francisco
Sponsor:
ClinicalTrials.gov Identifier:
NCT03086616
First Posted: March 22, 2017
Last Update Posted: December 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
The V Foundation for Cancer Research
Pacific Pediatric Neuro-Oncology Consortium
Information provided by (Responsible Party):
University of California, San Francisco
  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

Condition Intervention Phase
Diffuse Intrinsic Pontine Glioma Drug: Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI) Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Number of Participants with Adverse Events related to treatment [ Time Frame: 12 months ]
    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:
  • Overall Survival (OS) at 12 months (OS12) [ Time Frame: 12 months ]
    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.


Other Outcome Measures:
  • Distribution of Gadolinium [ Time Frame: 12 months ]
    Assessment of observed distribution of gadolinium compared to pre-treatment modeling of the drug distribution utilizing predictive imaging software.


Estimated Enrollment: 19
Actual Study Start Date: May 23, 2017
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Newly Diagnosed DIPG
Convection 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.
Drug: Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)
Nal-IRI will be given directly into the tumor using CED.
Other Name: Irinotecan Liposome Injection

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   3 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with newly diagnosed DIPG by 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 of 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 of the date of the completion of radiotherapy.
  • Prior Chemotherapy: 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.
  • 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 4 weeks prior to and no later than 14 weeks from the first CED treatment with liposomal-irinotecan. Standard focal radiation therapy will include 54 to 60 Gy by external beam radiotherapy to the brainstem.
  • Age ≥ 3 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 are receiving any other investigational agents or other tumor-directed therapy.
  • Patients with metastatic disease, including leptomeningeal or subarachnoid disseminated disease.
  • Patients with tumor morphology that predicts poor coverage of the majority of the tumor including bilateral thalamic involvement, >30% of estimated tumor volume outside the pons, or cysts that represent >50% of cross-sectional areas of the pons. Patients with evidence of cystic changes greater than 1 cm in diameter will be excluded. These subjects should be discussed with the study chairs.
  • 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(s) and study neurosurgeon prior to any planned CED treatment.
  • Patients with evidence of intra-tumoral hemorrhage > 5 mm maximal diameter. These subjects should be discussed with the study chair.
  • Patients with tumor morphology that predicts poor coverage of the majority of the tumor including bilateral thalamic involvement, >30% of estimated tumor volume outside the pons, or cysts that represent >50% of cross-sectional areas of the pons. Patients with evidence of cystic changes greater than 1 cm in diameter will be excluded. These subjects should be discussed with the study chair(s).
  • 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.
  • Untreated symptomatic hydrocephalus determined by treating physician.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03086616


Contacts
Contact: Sabine Mueller, MD, PhD, MAS (415) 476-3831 sabine.mueller@ucsf.edu
Contact: Ashley DeSilva, MPH (415) 502-1600 ashley.desilva@ucsf.edu

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94158
Contact: Sabine Mueller, MD    415-476-3831    sabine.mueller@ucsf.edu   
Sponsors and Collaborators
University of California, San Francisco
The V Foundation for Cancer Research
Pacific Pediatric Neuro-Oncology Consortium
Investigators
Study Chair: Sabine Mueller, MD, PhD, MAS University of California, San Francisco
  More Information

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03086616     History of Changes
Other Study ID Numbers: PNOC 009
160816 ( Other Identifier: University of California, San Francisco )
First Submitted: March 16, 2017
First Posted: March 22, 2017
Last Update Posted: December 1, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of California, San Francisco:
DIPG
CED
glioma

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Irinotecan
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action