MK0752 in Treating Young Patients With Recurrent or Refractory CNS Cancer

Brain and Central Nervous System Tumors Clinical Trial

Official title:

A Phase I Study of MK-0752 in Pediatric Patients With Recurrent or Refractory CNS Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00572182
• Other study ID #: CDR0000578114
• Secondary ID: U01CA081457PBTC-
• Status: Terminated
• Phase: Phase 1
• First received: December 11, 2007
• Last updated: March 2, 2012
• Start date: July 2008
• Est. completion date: February 2011

Study information

• Verified date: March 2012
• Source: Pediatric Brain Tumor Consortium
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

Primary

• To estimate the maximum tolerated dose (MTD) and recommended phase II dose of MK0752 administered for 3 consecutive days of every 7 days in 28 day courses to young patients with recurrent or refractory CNS malignancies (Dosing regimen 1 - closed to accrual 2/23/2010).

• To estimate the MTD and recommend a phase II dose of MK0752 administered once weekly in 28 day courses to young patients with recurrent or refractory CNS malignancies (Dosing regimen 2).

• To compared the MK0752 systemic exposure attained with each dosage level on the different dosing regimens.

Secondary

• To characterize the pharmacokinetics of MK0752.

• To document and describe toxicities associated with MK0752.

• To preliminarily define the antitumor activity of MK0752 within the confines of a phase I setting.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral MK0752 once daily on days 1-3, 8-10, 15-17, and 22-24 (dosing regimen 1 - closed to accrual 2/23/2010) or days 1, 8, 15, and 22 (dosing regimen 2). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment may be extended up to 19 courses if the patient is benefitting from the treatment.

Patients undergo blood sample collection periodically for pharmacokinetic studies.

After completion of study treatment, patients are followed for 30 days.

Other known NCT identifiers

• NCT00923208

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 33
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• MK-0752
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.

Locations

Country	Name	City	State
United States	NCI - Pediatric Oncology Branch	Bethesda	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Dan L. Duncan Cancer Center at Baylor College of Medicine	Houston	Texas
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Pediatric Brain Tumor Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose		First 28 days of treatment	Yes
Primary	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	No
Secondary	Pharmacokinetics	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	No
Secondary	Toxicity		From day 1 of treatment until off study	Yes
Secondary	Objective response rate	Brain imaging to assess tumor response to the treatment is performed at baseline, at the end of courses 2, 4, 6 and at the end of therapy.	End of courses 2, 4, 6 and at the end of treatment	No