|Phase I||Biomarker/Laboratory analysis, Treatment||Active||Under 19 at diagnosis||NCI||NCI-2011-02539|
10-C-0219, CDR0000687467, NCI-10-C-0219, 8449, NCT01226940
This phase I trial is studying side effects and best dose of lenalidomide when given together with radiation therapy in treating young patients with pontine glioma or high-grade glioma. 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
Further Study Information
I. To determine the tolerability and toxicity profile of oral lenalidomide when administered to children with newly diagnosed HGG and 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 MRI sequences for noninvasive monitoring of metabolic and biologic changes in malignant brain tumors with therapy.
II. To estimate 6-month and 12-month PFS and 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 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 (for a total of 54-59.4 Gy) and receive oral lenalidomide once daily for 6 weeks.
MAINTENANCE PHASE: Beginning two weeks after completion of radiotherapy, patients receive oral lenalidomide once daily on days 1-21.
Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Blood and cerebrospinal fluid samples may be collected periodically for pharmacokinetic and biologic studies.
After completion of study treatment, patients are followed up for 30 days and then every 3 months for 2 years.
- 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 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 is permitted
- Able to swallow capsules whole
- 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
- AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal
- Creatinine below age-adjusted maximum limits in the table below OR
- 0.8 mg/dl (patients =< 5 years of age)
- 1.0 mg/dl (patients 6 to =< 10 years of age)
- 1.2 mg/dl (patients 11 to =< 15 years of age)
- 1.5 mg/dl (patients > 15 years of age)
- Creatinine clearance >= 60 mL/min/1.73 m^2
- 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
- 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
- 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 woman 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; this protocol defines a female of childbearing potential as a sexually mature woman 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); This protocol defines FCCBP as females who have:
- Achieved menarche and/or breast development in Tanner stage 2 or greater
- Onset of fertility typically occurs within 3-12 months after menarche; menarche varies considerably from person to person, and thus no age cut off can be attributed; one of the primary tools used to follow a girl's progress through puberty is the Tanner staging system, which describes the pattern of development of the secondary sex characteristics; Tanner stage 2 corresponds to the beginning of breast development, which is the first visible sign of puberty in girls; breast development is estrogen stimulated, and since ovulation cannot occur without estrogen, Tanner stage 2 will be a reliable marker for the definition of fertility
- Has not undergone a hysterectomy or bilateral oophorectomy; NOTE: Amenorrhea following cancer therapy does not rule out childbearing potential
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.
- 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
- 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 completed resected with good margins
- Patients with a body surface area (BSA) =< 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
- PT, PTT, thrombin time, fibrinogen
- Protein C, protein S
- Factor V Leiden
- Prothrombin G20210A gene analysis
- Fasting serum homocysteine
- Lupus anticoagulant assays
- Anticardiolipin level
- Fasting serum homocysteine
- Anticardiolipin level
- LDL, HDL, triglycerides
- 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
- Known 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 CSF cytology) are excluded
Trial Lead Organizations/Sponsors
National Cancer Institute
|Katherine Warren||Principal Investigator|
|Ann and Robert H. Lurie Children's Hospital of Chicago|
|Stewart Goldman||Ph: 773-880-4562|
|NCI - Pediatric Oncology Branch|
|Katherine Warren||Ph: 301-435-4683|
|Children's Hospital at Montefiore|
|Adam S Levy||Ph: 718-741-2342|
|New Hyde Park|
|Schneider Children's Hospital|
|Mark P Atlas||Ph: 718-470-3470|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center|
|Michael N Needle||Ph: 212-305-8615|
|New York University Medical Center|
|Matthias A Karajannis||Ph: 212-263-4434|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01226940
Information obtained from ClinicalTrials.gov on January 21, 2013
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