Lenalidomide and Radiation Therapy in High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas
|First Received Date ICMJE||October 15, 2010|
|Last Updated Date||February 19, 2014|
|Start Date ICMJE||September 2010|
|Estimated Primary Completion Date||September 2016 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||To determine the tolerability and toxicity profile of lenalidomide when administered to children with newly diagnosed HGG and DIPG with concurrent radiation and to evaluate long-term tolerability of lenalidomide.|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01222754 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||To evaluate: MRI biologic changes, 6 and 12 progression free survival, angiogenic and or immunomodulatory biomarkers, rate of metastatic disease in patients treated with antiangiogenic therapy, steady state pharmacokinetics.|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Lenalidomide and Radiation Therapy in High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas|
|Official Title ICMJE||A Phase I Trial of Lenalidomide and Radiotherapy in Children With Diffuse Intrinsic Pontine Gliomas and High-grade Gliomas|
- 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.
- 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.
- 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.
Brain tumors are the most common solid neoplasm in childhood and the second most common group of pediatric cancers.
Standard therapeutic options for brain tumors consist of surgical resection, radiation therapy and chemotherapy; yet overall survival rates for malignant brain tumors remain low.
Radiation therapy plays a key role in the treatment of diffuse intrinsic pontine gliomas (DIPG) and high-grade gliomas (HGG), and thalidomide has been shown in an animal model to be a radiosensitizer.
Lenalidomide, a thalidomide analog with antiangiogenic, cytotoxic and immunomodulatory effects, is being evaluated for the treatment of CNS tumors, and has shown tolerability and activity in pediatric studies.
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.
To evaluate long-term tolerability of lenalidomide in children with newly-diagnosed HGG and DIPG.
To evaluate magnetic resonance imaging (MRI) sequences for noninvasive monitoring of metabolic and biologic changes in malignant brain tumors with therapy.
To estimate 6 month and 12 month progression free survival (PFS) and overall survival (OS) in this patient population.
To determine if angiogenic and/or immunomodulatory biomarkers in the blood and urine correlate with toxicity and disease response.
To determine the rate of CNS metastatic disease in patients treated with antiangiogenic chemotherapy.
To determine any correlation of steady state pharmacokinetics of lenalidomide with time to progression, number and type of toxicities, and dose limiting toxicities.
Children with newly diagnosed HGG or DIPG, less than 22 years of age, no prior chemotherapy or radiation therapy, and performance score greater than or equal to 60%.
Children with HGG must have an inoperable or incompletely resected tumor.
Clinical laboratory tests must be within stated limits.
There will be two phases to therapy on this study, the Radiation Phase and the Maintenance Phase. The MTD will be determined by tolerability during the Radiation Phase.
Eligible patients will receive radiation therapy five days per week to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide daily in a standard Phase I dose escalation design.
At the conclusion of radiation therapy, there will be a two week break followed by maintenance dosing of lenalidomide for 21 days of a 28 day course, until unacceptable toxicity, disease progression or completion of 24 courses of lenalidomide beyond radiotherapy.
Using a standard phase I dose escalation design, the total sample size and the study duration are expected to be 18-30 patients and 5-6 years, respectively.
Using a multi-center, standard phase I dose escalation design, the total sample size
and the study duration are expected to be 18 30 patients and 5-6 years, respectively
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||30|
|Estimated Completion Date||September 2016|
|Estimated Primary Completion Date||September 2016 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
-No prior chemotherapy or radiation therapy for HGG or DIPG is permitted. Prior chemotherapy or radiation therapy for treatment of other malignancies is permitted.
-Patients must be less than 22 years of age at the time of diagnosis.
Able to swallow capsules whole
Patients of childbearing potential:
--Definition of female of childbearing potential (FCBP)
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).
--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
----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
--Criteria for female children not of childbearing potential (FCNCBP)
This protocol defines FCNCBP as females:
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.
All patients or their legal guardians (if the patient is less than18 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.
Durable Power of Attorney:
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) 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.
|Ages||1 Year to 21 Years|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01222754|
|Other Study ID Numbers ICMJE||100219, 10-C-0219|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||April 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP