Lenalidomide and Radiation Therapy in High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas

NCT01222754 | Completed Phase 1 FDA Drug

• 2 other identifiers: 10021910-C-0219
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Children who are diagnosed with brain tumors known as high grade gliomas or diffuse intrinsic pontine gliomas are generally treated with radiation therapy and chemotherapy. However, these tumors are very difficult to cure, and the tumor frequently begins to grow again even after treatment or surgery. Researchers are interested in determining whether the anticancer drug lenalidomide, which has been used to treat other aggressive types of cancer, is a safe and effective additional treatment for children who are scheduled to receive radiation therapy to treat high grade gliomas or diffuse intrinsic pontine gliomas. Objectives: \- To determine the safety and effectiveness of lenalidomide, in conjunction with radiation therapy, as a treatment for children who have been diagnosed with high grade gliomas or diffuse intrinsic pontine gliomas. Eligibility: \- Children and adolescents up to 21 years of age who have been diagnosed with high grade gliomas or diffuse intrinsic pontine gliomas and have not had radiotherapy or chemotherapy. Design:

• Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies.
• Participants will have two phases of treatment: a lenalidomide plus radiation phase and a lenalidomide-only phase.
• During the radiation phase, participants will take lenalidomide daily and have 6 weeks of radiation therapy (five treatments per week). After the radiation therapy, participants will stop taking lenalidomide for 2 weeks before continuing to the next phase.
• During the lenalidomide-only phase, participants will take lenalidomide daily for 21 days, followed by 7 days without lenalidomide (28-day cycle of treatment). Participants will have up to 24 cycles of lenalidomide.
• Participants will have frequent blood tests during the first cycle of treatment, and will have imaging studies or other tests as required by the study researchers.
• Treatment will continue until the disease progresses, the participant chooses to leave the study, or the researchers end the study.

Conditions

Diffuse Intrinsic Pontine Glioma; Anaplastic Astrocytoma; High Grade Glioma

Keywords

Newly Diagnosed; DIPG; Radiation Therapy; CC-5013; XRT; Brain Tumor; Glioma; Pediatrics

Outcome Measures

Primary Outcomes (2)

• Tolerability

  The plasma steady state concentration (and CSF levels if available for other reasons) will be correlated with toxicities (type and incidence), time to progression and response.

  2 years

• Toxicity Profile

  We will also estimate the population parameters using nonlinear mixed effects modeling methods (NONMEM)

  2 years

Secondary Outcomes (5)

• Evaluate MRI Sequences

  3 years

• Progression-free survival

  4 years

• Overall Survival

  4 years

• Biomarkers & toxicity/disease response correlation

  3 years

• Pharmacokinetics correlation with progression and toxicities

  3 years

Study Arms (1)

1

EXPERIMENTAL

Radiation with Lenalidomide

Drug: Lenalidomide; Radiation: XRT, 54-59.4 Gy

Interventions

Lenalidomide DRUG

1. With radiation therapy five days per week, concurrent doses of lenalidomide daily in a standard Phase I dose escalation design. 2. Maintenance dosing of lenalidomide, post-radiation, for 21 days of a 28 day course.

1

XRT, 54-59.4 Gy RADIATION

Radiation therapy five days per week to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide

1

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• Patients who have had prior chemotherapy for this tumor.
• Patients with an HGG that was completed resected with good margins.
• Patients with a body surface area (BSA) less than or equal to 0.4 m(2) are excluded because the lowest dose of the medication is 5 mg in capsule form.
• Patients with a known coagulation disorder are excluded. Patients with a first-degree relative with a history of venous thrombosis before age 50 yrs or an arterial thrombosis before age 40 yrs must have the following testing performed prior to enrollment to exclude a heritable disorder. Patients with a suspected disorder will be excluded due to the potential increased risk of thrombosis.
• Patients who have had a thromboembolic event that is not line-related are excluded.
• Patients with any significant medical illnesses that, in the investigator s opinion, cannot be adequately controlled with appropriate therapy, would compromise a patient s ability to tolerate this therapy or result in inability to assess toxicity. This includes, but is not limited to uncontrolled intercurrent illness including ongoing or active infection, cardiac disease, renal impairment or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with a history of Toxic Epidermal Necrolysis (TEN) or Stevens-Johnson syndrome are excluded as this has occurred in patients receiving lenalidomide.
• Patients receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide (i.e. thalidomide).
• Patients with known hypersensitivity to anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate.
• Pregnant or breast feeding females:
• Pregnant women are excluded from this study because lenalidomide is in a class with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide.
• Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with lenalidomide. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Patients identified as needing spinal radiation at diagnosis (e.g. spinal metastasis or malignant cells identified on CSF cytology) are excluded due to the increased risk of myelosuppression.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Siffert J, Greenleaf M, Mannis R, Allen J. Pediatric brain tumors. Child Adolesc Psychiatr Clin N Am. 1999 Oct;8(4):879-903, x.

  PMID: 10553209 BACKGROUND

• Finlay JL, Boyett JM, Yates AJ, Wisoff JH, Milstein JM, Geyer JR, Bertolone SJ, McGuire P, Cherlow JM, Tefft M, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. J Clin Oncol. 1995 Jan;13(1):112-23. doi: 10.1200/JCO.1995.13.1.112.

  PMID: 7799011 BACKGROUND

• Freeman CR, Farmer JP. Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys. 1998 Jan 15;40(2):265-71. doi: 10.1016/s0360-3016(97)00572-5.

  PMID: 9457808 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Astrocytoma; Glioma; Brain Neoplasms

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• John W Glod, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2010
• First Posted: October 18, 2010
• Study Start: November 23, 2010
• Primary Completion: April 17, 2019
• Study Completion: April 17, 2019
• Last Updated: January 3, 2022

Record last verified: 2021-12

Locations

US (1)