MK0752 in Treating Young Patients With Recurrent or Refractory CNS Cancer

NCT00572182 | Terminated Phase 1 DMC

• 4 other identifiers: CDR0000578114U01CA081457PBTC-024NCI-09-C-0112
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 12

Brief Summary

RATIONALE: MK0752 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of MK0752 in treating young patients with recurrent or refractory CNS cancer.

Conditions

Brain and Central Nervous System Tumors

Keywords

recurrent childhood brain stem glioma; childhood central nervous system germ cell tumor; recurrent childhood cerebellar astrocytoma; recurrent childhood cerebral astrocytoma; childhood high-grade cerebral astrocytoma; childhood choroid plexus tumor; childhood craniopharyngioma; recurrent childhood ependymoma; recurrent childhood medulloblastoma; childhood oligodendroglioma; recurrent childhood pineoblastoma; recurrent childhood supratentorial primitive neuroectodermal tumor; childhood atypical teratoid/rhabdoid tumor; childhood spinal cord neoplasm; childhood infratentorial ependymoma; childhood supratentorial ependymoma; recurrent childhood visual pathway and hypothalamic glioma; childhood grade III meningioma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  First 28 days of treatment

• MK0752 systemic exposure

  Serial blood samples for pharmacokinetic studies of MK-0752 will be collected with the first dose of course 1 at pre-specified times.

  Day 1 of course 1

Secondary Outcomes (3)

• Pharmacokinetics

  Day 1 of course 1

• Toxicity

  From day 1 of treatment until off study

• Objective response rate

  End of courses 2, 4, 6 and at the end of treatment

Interventions

MK-0752 DRUG

This is a dose escalation study. Patients may receive 150, 200, 260 or 325 mg/m2 orally for 3 consecutive days of every 7 days for 28 days (dosing regimen 1 - closed to accrual 2/23/2010) or 800, 1000, 1400, or 1800 mg/m2 orally once weekly for 28 days (1 course). In the absence of unacceptable toxicity or disease progression, treatment may continue for 6 courses.

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically confirmed primary CNS tumor * Patients with intrinsic brain stem tumors do not require histologic verification, but must have radiographic evidence of progression * Recurrent disease or refractory to standard therapy * No histologically benign brain tumors (e.g., low-grade glioma) PATIENT CHARACTERISTICS: * Karnofsky performance status (PS) or Lansky PS 60-100% * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Absolute neutrophil count ≥ 1,000/μL * Platelet count ≥ 100,000/μL (unsupported) * Hemoglobin ≥ 8 g/dL (RBC transfusions allowed) * Creatinine clearance OR glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age as follows: * 0.8 mg/dL (≤ 5 years of age) * 1.0 mg/dL (\> 5 to ≤ 10 years of age) * 1.2 mg/dL (\> 10 to ≤ 15 years of age) * 1.5 mg/dL (\> 15 years of age) * Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age * ALT ≤ 2.5 times ULN for age * Albumin ≥ 2.5 g/dL * Sodium, potassium, magnesium, and calcium normal * Patients with neurological deficits are eligible provided these deficits are stable for ≥ 2 weeks prior to study registration * No clinically significant systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient's ability to tolerate study therapy or would likely interfere with the study procedures or results * No known hypersensitivity to MK0752 PRIOR CONCURRENT THERAPY: * Recovered from the acute toxic effects of all prior therapy * At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas) * At least 7 days since prior investigational or biologic agents * At least 3 weeks since prior investigational or biologic agents that have a prolonged half-life or for which the patient has experienced ≥ grade 2 myelosuppression in the treatment course preceding discontinuation of therapy * At least 3 half lives since prior monoclonal antibody therapy * At least 6 months since prior total body irradiation or craniospinal radiotherapy * At least 6 weeks since other prior substantial bone marrow irradiation * At least 2 weeks since prior local palliative radiotherapy (small volume) * At least 6 months since prior allogeneic bone marrow transplantation (BMT) * No evidence of active graft versus host disease * At least 3 months since prior autologous BMT or stem cell transplantation * At least 7 days since prior hematopoietic growth factors (filgrastim \[G-CSF\], sargramostim \[GM-CSF\], or erythropoietin) (14 days for long-acting formulations) * No prior MK0752 * No concurrent enzyme-inducing anticonvulsant drugs (EIACDs) * No other concurrent anticancer or investigational drug therapy * Concurrent dexamethasone allowed provided patient is on a stable or decreasing dose for ≥ 2 weeks prior to study registration

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

NCI - Pediatric Oncology Branch

Bethesda, Maryland, 20892, United States

Location

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Dan L. Duncan Cancer Center at Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Astrocytoma; Choroid Plexus Neoplasms; Familial ependymoma; Medulloblastoma; Oligodendroglioma; Rhabdoid Tumor; Spinal Cord Neoplasms; Optic Nerve Glioma

Interventions

3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Neuroectodermal Tumors, Primitive; Neoplasms, Complex and Mixed; Spinal Cord Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases

Study Officials

• Maryam Fouladi, MD

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: December 11, 2007
• First Posted: December 12, 2007
• Study Start: July 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: March 6, 2012

Record last verified: 2012-03

Locations

US (12)