Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03086616
Other study ID # 160816
Secondary ID NCI-2017-01829
Status Completed
Phase Phase 1
First received
Last updated
Start date October 31, 2017
Est. completion date October 4, 2021

Study information

Verified date April 2023
Source University of California, San Francisco
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Completed
Enrollment 6
Est. completion date October 4, 2021
Est. primary completion date October 4, 2021
Accepts healthy volunteers No
Gender All
Age group 2 Years and older
Eligibility 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 after, the date of the completion of focal 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. Patients less than 30 days from last chemotherapy dose should be discussed with the study chair(s). - Prior Radiation: 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 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 international normalized ratio (INR) or per institutional guidelines. - Adequate Renal Function Defined as: - Creatinine clearance or radioisotope glomerular filtration rate (GFR) = 70 milliliters (mL)/min/1.73 m2 or - A serum creatinine based on age/gender as follows: Age Maximum Serum Creatinine (mg/dL) Male Female 2 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 serum glutamate pyruvate transaminase (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. - 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 (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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Convection Enhanced Delivery (CED) of Nanoliposomal irinotecan (nal-IRI)
Nal-IRI will be given directly into the tumor using CED.

Locations

Country Name City State
United States University of California, San Francisco San Francisco California

Sponsors (3)

Lead Sponsor Collaborator
Sabine Mueller, MD, PhD Pacific Pediatric Neuro-Oncology Consortium, The V Foundation for Cancer Research

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Distribution of Gadolinium Assessment of observed distribution of gadolinium compared to pre-treatment modeling of the drug distribution utilizing predictive imaging software. 12 months
Primary Number of Participants Experiencing Treatment-Related Adverse Events (AE) 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. Descriptive statistics will be utilized to display the data on toxicity 12 months
Secondary Overall Survival (OS) at 12 months (OS12) 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. The primary analysis will be based on the Kaplan-Meier method. Kaplan-Meier estimates and the associated 95% confidence intervals (CI) will be calculated 12 months
See also
  Status Clinical Trial Phase
Completed NCT01922076 - Adavosertib and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas Phase 1
Recruiting NCT05476939 - Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0 Phase 3
Terminated NCT03330197 - A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG Phase 1/Phase 2
Terminated NCT03690869 - REGN2810 in Pediatric Patients With Relapsed, Refractory Solid, or Central Nervous System (CNS) Tumors and Safety and Efficacy of REGN2810 in Combination With Radiotherapy in Pediatric Patients With Newly Diagnosed or Recurrent Glioma Phase 1/Phase 2
Active, not recruiting NCT02992015 - Gemcitabine in Newly-Diagnosed Diffuse Intrinsic Pontine Glioma Early Phase 1
Terminated NCT01182350 - Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG) Phase 2
Recruiting NCT04837547 - PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy Phase 1
Active, not recruiting NCT04911621 - Adjuvant Dendritic Cell Immunotherapy for Pediatric Patients With High-grade Glioma or Diffuse Intrinsic Pontine Glioma Phase 1/Phase 2
Not yet recruiting NCT06333899 - Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion Early Phase 1
Completed NCT00879437 - Valproic Acid, Radiation, and Bevacizumab in Children With High Grade Gliomas or Diffuse Intrinsic Pontine Glioma Phase 2
Active, not recruiting NCT02420613 - Vorinostat and Temsirolimus With or Without Radiation Therapy in Treating Younger Patients With Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma Phase 1
Recruiting NCT01837862 - A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas Phase 1/Phase 2
Not yet recruiting NCT06093165 - RE-irradiation of Diffuse MIdline Glioma paTients N/A
Withdrawn NCT03632317 - A Study of Panobinostat in Combination With Everolimus for Children and Young Adults With Gliomas Phase 2
Completed NCT02502708 - Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients With Progressive Primary Malignant Brain Tumors Phase 1
Recruiting NCT02233049 - Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication Phase 2
Completed NCT00996723 - Clinical Trial Evaluating the Combination of Vandetanib and Dasatinib During and After Radiation Therapy (RT) in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) Phase 1
Recruiting NCT05009992 - Combination Therapy for the Treatment of Diffuse Midline Gliomas Phase 2
Recruiting NCT04049669 - Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG Phase 2
Recruiting NCT05298995 - GD2-CAR T Cells for Pediatric Brain Tumours Phase 1