Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01553149
First received: March 10, 2012
Last updated: July 28, 2014
Last verified: June 2014
  Purpose

This randomized phase II trial studies low-dose or high-dose lenalidomide to see how well it works in treating younger patients with recurrent, refractory, or progressive juvenile pilocytic astrocytomas or optic nerve pathway gliomas. Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor.


Condition Intervention Phase
Neurofibromatosis Type 1
Recurrent Childhood Pilocytic Astrocytoma
Recurrent Childhood Visual Pathway Glioma
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized Trial of Lenalidomide (NSC # 703813) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response - best response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The response rate will be calculated as the ratio of the number of patients who demonstrate response (CR or PR) divided by the number of patients evaluable for response.


Secondary Outcome Measures:
  • Time to treatment failure (EFS) [ Time Frame: Time from study enrollment to tumor progression, tumor recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 5 years ] [ Designated as safety issue: No ]
    Standard survival methods will be used for analysis of EFS. Analyses include log rank tests and the product-limit (Kaplan-Meier) estimate for estimation of EFS probability.

  • Time to death (overall survival [OS]) [ Time Frame: Time from study enrollment to death from any cause ] [ Designated as safety issue: No ]
    Standard survival methods will be used for analysis of OS. Analyses include log rank tests and the product-limit (Kaplan-Meier) estimate for estimation of OS probability.


Estimated Enrollment: 80
Study Start Date: March 2012
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive low-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Experimental: Arm II
Patients receive high-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the objective response rate in children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with Regimen A low-dose (20 mg/m²/dose) or Regimen B high-dose (115 mg/m²/dose) lenalidomide.

SECONDARY OBJECTIVES:

I. To estimate the event-free survival (EFS) (based on standard two-dimensional tumor measurements, determined by each institution) of children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas and optic pathway gliomas who are treated with lenalidomide.

II. To compare response categories and EFS across the 3 magnetic resonance (MR) sequences (T2-weighted, fluid attenuated inversion recovery [FLAIR], T1-weighted post-contrast).

III. To correlate steady-state pharmacokinetics of lenalidomide (1 sample obtained between Days 5-21) with objective response and EFS.

IV. To evaluate toxicities of long-term lenalidomide use.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I (regimen A): Patients receive low-dose lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

ARM II (regimen B): Patients receive high-dose lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection between days 5-21 during course 1 for pharmacokinetic studies.

After completion of study treatment, patients are followed up for up to 5 years.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a pilocytic astrocytoma or optic pathway glioma that has relapsed, progressed, or become refractory to conventional therapy; patients with neurofibromatosis (NF-1) are eligible
  • Patients must have histologic verification of malignancy; histologic confirmation for patients with optic pathway gliomas will not be required
  • Patients must have measurable residual disease, defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI); for a lesion to be considered measurable, it must be at least twice the slice thickness on MRI (i.e., visible on more than one slice)
  • To document the degree of residual tumor, the following must be obtained:

    • All patients must have a brain MRI with and without contrast (gadolinium) within 1 week prior to study enrollment; for patients on steroids, baseline MRI scans must be performed after at least 1 week at a stable or decreasing dose of steroids
    • All patients with a history of spinal or leptomeningeal disease, and those patients with symptoms suspicious of spinal disease, must have a spine MRI with and without contrast (gadolinium) performed within 2 weeks prior to study enrollment
  • Patients must have been treated with two or fewer anti-cancer regimens, including chemotherapy, biologic agents, immunotherapy, vaccines, monoclonal antibodies, or radiation therapy

    • At least one prior treatment regimen must have included carboplatin
    • Patients who have received prior radiation therapy for this tumor are eligible
  • Patients must have a body surface area (BSA) ≥ 0.4 m² at the time of study enrollment
  • Patients must have a Lansky or Karnofsky performance status score of ≥ 60%; use Karnofsky for patients> 16 years of age and Lansky for patients ≤ 16 years of age
  • Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL
  • Platelet count ≥ 100,000/μL (transfusion independent)
  • Hemoglobin ≥ 8.0 g/dL (may receive red blood cell [RBC] transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate(GFR) ≥ 70 mL/min OR a serum creatinine based on age/gender as follows:

    • 0.4 mg/dL (1 month to < 6 months of age)
    • 0.5 mg/dL (6 months to < 1 year of age)
    • 0.6 mg/dL (1 to < 2 years of age)
    • 0.8 mg/dL (2 to < 6 years of age)
    • 1.0 mg/dL (6 to 10 years of age)
    • 1.2 mg/dL (10 to < 13 years of age)
    • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
    • 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
  • Serum glutamic pyruvate transaminase(SGPT) (alanine aminotransferase [ALT]) ≤ 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin ≥ 2 g/dL
  • No evidence of dyspnea at rest and a pulse oximetry > 94% if there is clinical indication for determination
  • Patients must be able to swallow intact capsules
  • Not pregnant or breastfeeding

    • Lactating females are not eligible unless they have agreed not to breastfeed their infants while receiving protocol therapy and for 28 days after the last dose of lenalidomide
  • Female patients of childbearing potential are not eligible unless they commit to complete abstinence or have been on 2 methods of birth control, including 1 highly effective method and 1 additional method at the same time (unless committing to complete abstinence of heterosexual intercourse), at least 28 days (4weeks) prior to study enrollment; sexually active females must also agree to remain on 2 methods of birth control during treatment (including during dose interruptions) and continuing for at least 28 days after the completion of protocol therapy; examples of methods of contraception are as follows:

    • Highly effective methods (must use at least 1):

      • Intrauterine device (IUD)
      • Hormonal (prescription birth control pills, injections, implants)
      • Tubal ligation
      • Partner's vasectomy
    • Additional effective methods:

      • Male condom
      • Diaphragm
      • Cervical cap
    • The two methods of birth control requirement applies to all sexually active females unless they have not had a menstrual period in the preceding 24 consecutive months or have undergone a hysterectomy or bilateral oophorectomy
  • Female patients of childbearing potential (including those who commit to complete abstinence) are not eligible unless they agree to ongoing pregnancy testing and counseling every28 days about pregnancy precautions and risks of fetal exposure
  • Male patients of child-fathering potential are not eligible unless they have agreed to use latex condoms during intercourse with a woman of childbearing potential while receiving treatment and for 28 days thereafter
  • Patients with a history of thromboembolism unrelated to a central line or patients with a known predisposition syndrome for thromboembolism are not eligible
  • Patients who have an uncontrolled or untreated infection are not eligible
  • Patients with known overt cardiac disease including, but not limited to, a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, Grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmia are not eligible
  • Patients with a significant systemic illness that is not well-controlled, in the opinion of the treating physician, are not eligible
  • See Disease Characteristics
  • Patients must have recovered (to common terminology criteria [CTC] v.4.0 ≤ Grade 1 unless indicated below) from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, with the exception of alopecia, weight changes, and Grade I or II lymphopenia

    • Must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study(6 weeks if prior nitrosourea or mitomycin C)
    • At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
    • At least 42 days after the completion of any type of immunotherapy, e.g., tumor vaccines
    • At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
    • Patients must have had their last fraction of craniospinal radiotherapy (RT)≥ 6 months prior to study entry and their last fraction of focal RT ≥ 4 weeks prior to study entry; if the lesion used for on-study criteria is in the radiation field, there must be evidence of tumor progression after radiation therapy was completed
    • Study-specific limitations on prior therapy:

      • Patients who have received prior thalidomide are eligible if all acute thalidomide-related toxicity has resolved
      • Patients must not have received lenalidomide previously
  • Must not have received growth factor(s) within 2 weeks of entry onto this study
  • Patients who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to baseline MRI
  • Concurrent cancer therapy, including chemotherapy, radiation therapy, immunotherapy, or biologic therapy, may NOT be administered to patients while on this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01553149

  Show 115 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Katherine Warren Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01553149     History of Changes
Other Study ID Numbers: NCI-2012-00703, NCI-2012-00703, CDR0000728296, COG-ACNS1022, ACNS1022, ACNS1022, U10CA098543
Study First Received: March 10, 2012
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Glioma
Neurofibromatoses
Neurofibromatosis 1
Osteitis Fibrosa Cystica
Optic Nerve Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neurofibroma
Nerve Sheath Neoplasms
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Optic Nerve Neoplasms
Cranial Nerve Neoplasms
Nervous System Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on July 29, 2014