Lenalidomide and Radiation Therapy in Treating Children with Pontine Glioma or High-Grade Glioma
This phase I trial studies the side effects and best dose of lenalidomide when given together with radiation therapy in treating younger patients with pontine glioma or glioma that tends to grow and spread more quickly (high-grade). Lenalidomide may stop the growth of gliomas by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving lenalidomide together with radiation therapy may kill more tumor cells.
- Histological confirmation of a high-grade malignant glioma is required; histologic diagnoses include, but are not limited to, anaplastic astrocytoma and glioblastoma multiforme; patients with DIPG are exempt from histologic verification if they have typical MRI findings of DIPG (i.e. hypo- or isointense on T1-weighted imaging, hyperintense on fluid-attenuated inversion recovery [FLAIR] or T2-weighted imaging, epicenter in the pons, > 50% of pons involved) in the face of a typical clinical presentation
- Inoperable tumor or residual disease after resection
- No prior chemotherapy or radiation therapy for HGG or DIPG is permitted; prior chemotherapy or radiation therapy for treatment of other malignancies is permitted
- Able to swallow whole capsules
- Patients should have a Karnofsky/Lansky score of greater than or equal to 60; patients who require special assistance due to tumor-related paralysis, but who are out of bed during the day will be considered ambulatory for the purpose of calculating the performance score; patients must be able to communicate any symptoms
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
- Total bilirubin < 1.5 x upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine below age-adjusted maximum limits in the table below OR creatinine clearance >= 60 mL/min/1.73 m^2 * 0.8 mg/dl (patients =< 5 years of age) * 1.0 mg/dl (patients 5 < age =< 10 years of age) * 1.2 mg/dl (patients 10 < age =< 15 years of age) * 1.5 mg/dl (patients > 15 years of age)
- Females only: * Urine or serum pregnancy test negative
- No overt renal, hepatic, cardiac or pulmonary disease
- Newly diagnosed patients may need to be on steroids due to surgery or control of neurologic symptoms; patients on steroids postoperatively or for control of tumor-related edema are eligible, but attempts to keep patients on the lowest dose necessary to control symptoms should be made
- This protocol defines a female of childbearing potential (FCCBP) as a sexually mature female (at least Tanner 2) who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) * Criteria for female children of childbearing potential (FCCBP) ** This protocol defines FCCBP as females who have: *** Achieved menarche and/or breast development in Tanner stage 2 or greater *** Has not undergone a hysterectomy or bilateral oophorectomy; *** Note: amenorrhea following cancer therapy does not rule out childbearing potential * Criteria for female children not of childbearing potential (FCBCBP) ** This protocol defines FCNCBP as females: *** Who have not yet experienced menarche or breast development in Tanner stage 2 *** Who have undergone a hysterectomy or bilateral oophorectomy * Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days and again within 24 hours prior to starting course 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature female (Tanner stage 2) who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure * Male subjects ** Appropriate male subjects (i.e. those who have reached puberty and are sexually active) will be counseled regarding birth control methods; they must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy ** Appropriate male patients will be given a reproductive risks handout and counseled by a provider; for sexually active patients, the counseling session, consent and counseling checklist will be documented monthly
- All patients or their legal guardians (if the patient is < 18 years old) or durable power of attorney (DPA) must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study; when appropriate, pediatric patients will be included in all discussions in order to obtain verbal assent
- Assignment of DPA to a family member or guardian should be offered to all patients 18 years of age or older
- Signed informed consent according to institutional guidelines must be obtained
- Patients who have had prior chemotherapy for this tumor
- Patients with an HGG that was completely resected with good margins
- Patients with a body surface area (BSA) =< 0.4 m^2 are excluded
- Patients with a known coagulation disorder are excluded; patients with a first-degree relative with a history of venous thrombosis before age 50 years (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
- 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
- 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 women are excluded from this study; breastfeeding should be discontinued if the mother is treated with lenalidomide
- Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients identified as needing spinal radiation at diagnosis (e.g. spinal metastasis or malignant cells identified on cerebrospinal fluid [CSF] cytology) are excluded
Locations & Contacts
Contact: Stewart Goldman
Contact: Katherine Elizabeth Warren
Phone: 301-435-4683 Email: firstname.lastname@example.org
Contact: Katherine Elizabeth Warren
Phone: 301-435-4683 Email: email@example.com
New Hyde Park
Contact: Mark P. Atlas
Contact: Julia Glade-Bender
Phone: 212-305-5808 Email: firstname.lastname@example.org
Contact: Michael N. Needle
Contact: Matthias A. Karajannis Email: email@example.com
Trial Objectives and Outline
I. To determine the tolerability and toxicity profile of oral lenalidomide when administered to children with newly diagnosed high-grade glioma (HGG) and diffuse infiltrative pontine glioma (DIPG) with concurrent radiation at doses up to 116 mg/m^2/day.
II. To evaluate long-term tolerability of lenalidomide in children with newly diagnosed HGG and DIPG.
I. To evaluate magnetic resonance imaging (MRI) sequences for noninvasive monitoring of metabolic and biologic changes in malignant brain tumors with therapy.
II. To estimate 6-month and 12-month progression free survival (PFS) and overall survival (OS) in this patient population.
III. To determine if angiogenic and/or immunomodulatory biomarkers in the blood and urine correlate with toxicity and disease response.
IV. To determine the rate of central nervous system (CNS) metastatic disease in patients on antiangiogenic chemotherapy.
V. To determine any correlation of steady-state pharmacokinetics of lenalidomide with time to progression, number and type of toxicities, and dose-limiting toxicities.
OUTLINE: This is a dose-escalation study of lenalidomide.
RADIATION PHASE: Patients undergo radiotherapy 5 days per week for 6 weeks and receive lenalidomide orally (PO) once daily (QD) for 6 weeks.
MAINTENANCE PHASE: Beginning two weeks after completion of radiotherapy, patients receive lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 3 months for 2 years.
Trial Phase & Type
NCI - Center for Cancer Research
Katherine Elizabeth Warren
Secondary IDs 10-C-0219, NCI-2011-02539, 100219, P10687, NCI-10-C-0219, CDR0000687467
Clinicaltrials.gov ID NCT01226940