RO4929097 in Children With Relapsed/Refractory Solid or CNS Tumors, Lymphoma, or T-Cell Leukemia

NCT01236586 | Withdrawn Phase 1

• 2 other identifiers: 11001711-C-0017
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Background: \- The anti-cancer drug RO4929097 is being tested for its ability to block blood vessel growth to tumors and slow or stop the growth of cancer cells. However, it has been used in only a small number of adults and has not yet been tested in children. Researchers are interested in determining whether RO4929097 is a safe and effective treatment for tumors or leukemia that has not responded to standard treatment. Objectives: \- To determine the safety and effectiveness of RO4929097 as a treatment for children and adolescents who have been diagnosed with certain kinds of cancer that have not responded to standard treatment. Eligibility: \- Children, adolescents, and young adults between 1 and 21 years of age who have been diagnosed with solid, nervous system, or blood-based cancers that have not responded to standard treatment. Design:

• Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies. Some participants may also have a bone marrow biopsy to evaluate the state of their disease.
• Participants will be separated into three groups: One group will receive RO4929097 alone, and the other two will receive RO4929097 in combination with the immune-suppressing drug dexamethasone.
• RO4929097 will be given as tablets on one of two schedules: days 1 to 3 of every week (Schedule A) or days 1 to 5 of every week (Schedule B). The dosing schedule will be determined randomly. Every 4-week treatment period is one cycle, and participants may receive RO4929097 for up to 24 cycles.
• Participants will have frequent blood and urine tests and imaging studies to evaluate the progress of treatment, and will be asked to keep a diary to monitor any side effects.

Conditions

Lymphoma; Brain Neoplasms; Sarcoma; Osteosarcoma; Wilm's Tumor

Keywords

Maximum Tolerated Dose; Toxicity; Pharmacokinetics; NOTCH Signaling Pathway; Expression of JAGGED 1 and 2; Cancer; Solid Tumor; Brain Tumor; Wilms Tumor; Osteosarcoma; Lymphoma

Outcome Measures

Primary Outcomes (1)

• The primary outcomes of this study are self-reported fatigue, depression, and quality of life scores of patients before, at midpoint, and at completion of each cycle of their cancer treatment.

Secondary Outcomes (1)

• Cytokine profile

Interventions

RO4929097 DRUG

Dexamethasone DRUG

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

* ELIGIBILITY CRITERIA: * Patients greater than 12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with intrinsic brain stem tumors, optic pathway gliomas) of measureable or evaluable relapsed or refractory disease. Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival with an acceptable quality of life. * Subjects must be able to swallow tablets. * Patients who are pregnant, are known to be serologically positive for Hepatitis A, B, C, or have a history of liver disease, or have prolonged QTc are not eligible.

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

St. Jude Childrens Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (3)

• Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999 Apr 30;284(5415):770-6. doi: 10.1126/science.284.5415.770.

  PMID: 10221902 BACKGROUND

• Curry CL, Reed LL, Golde TE, Miele L, Nickoloff BJ, Foreman KE. Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells. Oncogene. 2005 Sep 22;24(42):6333-44. doi: 10.1038/sj.onc.1208783.

  PMID: 15940249 BACKGROUND

• Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006 Sep;7(9):678-89. doi: 10.1038/nrm2009.

  PMID: 16921404 BACKGROUND

MeSH Terms

Conditions

Lymphoma; Brain Neoplasms; Sarcoma; Osteosarcoma; Wilms Tumor; Neoplasms

Interventions

2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 5, 2010
• First Posted: November 8, 2010
• Study Start: October 8, 2010
• Primary Completion: April 13, 2011
• Study Completion: April 13, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-04-13

Locations

US (2)