Irofulven in Treating Children With Recurrent or Refractory Solid Tumors

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00003370

Collaborator

(none)

Enrollment

Locations

Arm

0.2

Patients Per Site

Study Details

Study Description

Brief Summary

Phase I trial to study the effectiveness of irofulven in treating children with recurrent or refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells so they stop growing or die.

Condition or Disease	Intervention/Treatment	Phase
Unspecified Childhood Solid Tumor, Protocol Specific	Drug: irofulven	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose and dose limiting toxicity of 6-hydroxymethylacylfulvene (MGI-114) in pediatric patients with recurrent or refractory solid tumors.
Determine the incidence and severity of other toxic effects of MGI-114. III. Determine a safe and tolerable dose of MGI-114 to be used in phase II studies.
Determine the pharmacokinetics of MGI-114 in these patients. V. Determine preliminary evidence of antitumor activity of MGI-114 against recurrent or refractory pediatric solid tumors.

OUTLINE: This is a dose escalation study. If the dose limiting toxicity is myelosuppression in stratum 1, then stratum 1 is closed and stratum 2 opens.

Stratum 2 consists of the following: patients receiving no more than 2 prior chemotherapy regimens; patients who have not received prior central axis radiation or bone marrow transplantation; and patients with no known bone marrow involvement. Patients receive intravenous 6-hydroxymethylacylfulvene over 10 minutes daily for 5 days. The course is repeated every 28 days unless disease progression or unacceptable toxic effects are observed. Patients with stable or responding disease may receive up to 1 year of therapy. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose. Dose escalation will not occur until all patients within a cohort have been observed for 28 days from day 1 of therapy. Patients are followed until death.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Trial of MGI 114 in Children With Solid Tumors: A Pediatric Oncology Group Phase I Cooperative Agreement Study

Study Start Date :

Aug 1, 1998

Actual Primary Completion Date :

Mar 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I If the dose limiting toxicity is myelosuppression in stratum 1, then stratum 1 is closed and stratum 2 opens. Stratum 2 consists of the following: patients receiving no more than 2 prior chemotherapy regimens; patients who have not received prior central axis radiation or bone marrow transplantation; and patients with no known bone marrow involvement. Patients receive intravenous 6-hydroxymethylacylfulvene over 10 minutes daily for 5 days. The course is repeated every 28 days unless disease progression or unacceptable toxic effects are observed. Patients with stable or responding disease may receive up to 1 year of therapy. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose. Dose escalation will not occur until all patients within a cohort have been observed for 28 days from day 1 of therapy. Patients are followed until death.	Drug: irofulven

Arm

Intervention/Treatment

Experimental: Arm I

If the dose limiting toxicity is myelosuppression in stratum 1, then stratum 1 is closed and stratum 2 opens. Stratum 2 consists of the following: patients receiving no more than 2 prior chemotherapy regimens; patients who have not received prior central axis radiation or bone marrow transplantation; and patients with no known bone marrow involvement. Patients receive intravenous 6-hydroxymethylacylfulvene over 10 minutes daily for 5 days. The course is repeated every 28 days unless disease progression or unacceptable toxic effects are observed. Patients with stable or responding disease may receive up to 1 year of therapy. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the next lower dose is declared the maximum tolerated dose. Dose escalation will not occur until all patients within a cohort have been observed for 28 days from day 1 of therapy. Patients are followed until death.

Drug: irofulven

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically proven recurrent or refractory solid tumors
No leukemia
Patients with brain tumors are not eligible until the first 2 patients at each dose level are evaluable for toxicity

PATIENT CHARACTERISTICS:

Age: 21 and under
Performance status: Karnofsky 50-100% Lansky play scale 50-100% (for infants)
Life expectancy: At least 8 weeks
Absolute neutrophil count at least 1,000/mm3
Hemoglobin at least 9 g/dL
Platelet count at least 75,000/mm3
Bilirubin less than 1.5 mg/dL
SGPT less than 5 times upper limit of normal
Creatinine normal for age OR GFR at least 70 mL/min
Cardiac shortening fraction at least 27% OR institutional normal OR cardiac ejection fraction greater than 50% OR institutional normal
Neurologic deficits in patients with CNS tumors must be stable for at least 2 weeks
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after the study
No uncontrolled infection

PRIOR CONCURRENT THERAPY:

At least 1 week since prior growth factor therapy and recovered
At least 6 months since prior bone marrow transplantation and no evidence of graft versus host disease
At least 2 weeks since prior myelosuppressive chemotherapy and recovered
At least 6 weeks since prior nitrosourea and recovered
At least 2 weeks on stable dexamethasone for patients with CNS tumors
No concurrent chemotherapy
At least 2 weeks since prior palliative radiotherapy (small port)
At least 6 months since prior substantial bone marrow radiation
At least 6 months since total abdominal, pelvic, chest, mantle, and Y ports radiotherapy
No other concurrent anticancer therapy or investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	City of Hope National Medical Center	Duarte	California	United States	91010
3	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
4	Children's Hospital Los Angeles	Los Angeles	California	United States	90027-0700
5	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
6	Children's Hospital of Orange County	Orange	California	United States	92868
7	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94143-0128
8	Stanford University Medical Center	Stanford	California	United States	94305-5408
9	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
10	University of Florida Health Science Center	Gainesville	Florida	United States	32610-0296
11	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
12	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois	United States	60611-3013
13	Children's Memorial Hospital, Chicago	Chicago	Illinois	United States	60614
14	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5289
15	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
16	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
17	Boston Floating Hospital Infants and Children	Boston	Massachusetts	United States	02111
18	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
19	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
20	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
21	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
22	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
23	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
24	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
25	Cardinal Glennon Children's Hospital	Saint Louis	Missouri	United States	63104
26	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
27	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
28	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
29	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
30	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
31	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
32	Columbia Presbyterian Hospital	New York	New York	United States	10032
33	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
34	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
35	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio	United States	45229-3039
36	Children's Hospital of Columbus	Columbus	Ohio	United States	43205-2696
37	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73190
38	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
39	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
40	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
41	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
42	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
43	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
44	Texas Children's Cancer Center	Houston	Texas	United States	77030-2399
45	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
46	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
47	Primary Children's Medical Center	Salt Lake City	Utah	United States	84113
48	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
49	Veterans Affairs Medical Center - Huntington	Huntington	West Virginia	United States	25704
50	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
51	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
52	Royal Children's Hospital	Parkville	Victoria	Australia	3052
53	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
54	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
55	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec	Canada	H3H 1P3
56	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair: Gail C. Megason, MD, University of Mississippi Cancer Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

National Cancer Institute (NCI)

ClinicalTrials.gov Identifier:

NCT00003370

Other Study ID Numbers:

NCI-2012-01838
POG-9772
CDR0000066359

First Posted:

Feb 9, 2004

Last Update Posted:

Feb 5, 2013

Last Verified:

May 1, 2006

Keywords provided by National Cancer Institute (NCI)

unspecified childhood solid tumor, protocol specific

Additional relevant MeSH terms:

Neoplasms

Irofulven

Study Results

No Results Posted as of Feb 5, 2013