Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia



Status:Archived
Conditions:Cancer, Brain Cancer, Blood Cancer, Lymphoma, Leukemia
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any
Updated:7/1/2011
Start Date:March 2010

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A Phase 1/2 Study of RO4929097, an Oral Small Molecule Inhibitor of Gamma-Secretase, in Children With Relapsed/Refractory Solid or CNS Tumors, Lymphoma, or T-Cell Leukemia


RATIONALE: Gamma-secretase inhibitor RO4929097 may stop the growth of cancer cells by
blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II clinical trial is studying the side effects and best dose of
gamma-secretase inhibitor RO4929097 and to see how well it works in treating young patients
with relapsed or refractory solid tumors, CNS tumors, lymphoma, or T-cell leukemia.


OBJECTIVES:

Primary

- To estimate the maximum-tolerated dose (MTD) and recommend a phase II dose of
gamma-secretase inhibitor RO4929097 administered orally to children with relapsed or
refractory solid tumors or lymphoma on two schedules: once daily orally on a 3-day
on/4-day off weekly schedule (schedule A) or once daily for 5 consecutive days weekly
schedule (schedule B).

- To define and describe the toxicities of this drug administered on these schedules to
children with relapsed or refractory solid tumors, lymphoma, or T-cell leukemia.

- To estimate the MTD and recommended phase II dose of gamma-secretase inhibitor
RO4929097 administered with dexamethasone.

- To define and describe the toxicities of gamma-secretase inhibitor RO4929097
administered with dexamethasone.

- To characterize the pharmacokinetics of gamma-secretase inhibitor RO4929097 in children
with refractory cancer.

Secondary

- To preliminarily define the antitumor activity of gamma-secretase inhibitor RO4929097
in children with solid or CNS tumors and lymphoma within the confines of a phase I
study.

- To obtain initial efficacy data on the antitumor activity of gamma-secretase inhibitor
RO4929097 when combined with dexamethasone in children with relapsed-refractory T-cell
leukemia (T-acute lymphoblastic leukemia [ALL]).

- To study the effect of gamma-secretase inhibitor RO4929097 on Hes1 (hairy/enhancer of
split) and other components of the Notch signaling pathway in peripheral blood
mononuclear cells and/or T-ALL blasts. (exploratory)

- To examine archival tumor samples for expression of JAGGED1, JAGGED2, cleaved NOTCH1,
and HES1, and HES5 by IHC and for amplification of NOTCH1 or NOTCH2 using FISH
analysis. (exploratory)

- To preliminarily assess changes following treatment with gamma-secretase inhibitor
RO4929097 using FDG PET imaging. (exploratory)

OUTLINE: This is a multicenter, phase I, dose-escalation study of gamma-secretase inhibitor
RO4929097 followed by a phase II study. Patients are enrolled sequentially to group A or B.

- Group A: Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days
1-3, 8-10, 15-17, and 22-24. Treatment repeats every 28 days for up to 24 courses in
the absence of disease progression or unacceptable toxicity.

- Group B: Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days
1-5, 8-12, 15-19, and 22-26. Treatment repeats every 28 days for up to 24 courses in
the absence of disease progression or unacceptable toxicity.

Patients may also receive concurrent oral dexamethasone twice daily on the days of
gamma-secretase inhibitor RO4929097 administration.

Once the MTD or recommended phase II dose of RO4929097 plus dexamethasone in children with
solid tumors, including CNS tumors, or lymphoma has been identified, this dose is used for
patients with relapsed-refractory T-ALL (phase 2 portion of the study) to evaluate RO4929097
in combination with dexamethasone using one of the studied schedules.

Blood, plasma, bone marrow, and tumor tissue samples may be collected at baseline and
periodically during the first course for correlative lab and tumor studies, including
pharmacokinetics.

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


We found this trial at
22
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722 W 168th St
New York, New York 10032
(212) 305-2500
Columbia Presbyterian Med Ctr On January 1, 1998, The New York Hospital publicly announced its...
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Ann Arbor, MI 48109Bus: -
Ann Arbor, Michigan 48109
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1405 Clifton Road Northeast
Atlanta, Georgia 30322
(404) 785-6000
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus...
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1802 6th Avenue South
Birmingham, Alabama 35294
(205) 934-4011
UAB Comprehensive Cancer Center One of the nation’s leading cancer research and treatment centers, the...
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300 Longwood Avenue
Boston, Massachusetts 02115
617-355-6000
Children's Hospital - Boston Boston Children's Hospital is a 395-bed comprehensive center for pediatric health...
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450 Brookline Ave
Boston, Massachusetts 2215
(617) 632-3000
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Founded in 1997, Dana-Farber/Harvard Cancer Center (DF/HCC) was...
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas From its...
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425 E River Pkwy # 754
Minneapolis, Minnesota 55455
612-624-2620
Masonic Cancer Center at University of Minnesota The Masonic Cancer Center was founded in 1991....
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3181 SW Sam Jackson Park Rd
Portland, Oregon 97239
(503) 494-5058
Knight Cancer Institute at Oregon Health and Science University Cancer takes many forms. Although cancer...
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4800 Sand Point Way Northeast
Seattle, Washington 98105
(206) 987-2000
Children's Hospital and Regional Medical Center - Seattle Seattle Children
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136 Mountainview Blvd
Basking Ridge, New Jersey 7920
(908) 542-3000
Memorial Sloan-Kettering Cancer Center - Basking Ridge At Memorial Sloan Kettering Basking Ridge, we offer...
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Boston, Massachusetts 02115
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1 Baylor Plaza
Houston, Texas 77030
(713) 798-4951
Baylor School of Medicine Baylor College of Medicine is a health sciences university that creates...
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Indianapolis, Indiana 46202
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Pittsburgh, Pennsylvania 15213
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660 S Euclid Ave
St. Louis, Missouri 63110
(800) 600-3606
Siteman Cancer Center The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University...
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