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

NCT01088763 | Terminated Phase 1

• 5 other identifiers: NCI-2011-02024COG-ADVL0919CDR0000667505ADVL0919U01CA097452
• Study Type: interventional
• Target: 129
• Locations: 2 countries
• Sites: 12

Brief Summary

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

Conditions

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of RO4929097 determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)

  28 days

• MTD of RO4929097 administered with dexamethasone determined according to DLTs graded using CTCAE v4.0

  28 days

Secondary Outcomes (1)

• Antitumor activity of RO4929097 with or without dexamethasone assessed by Response Evaluation Criteria for Solid Tumors (RECIST)

  Up to 30 days

Study Arms (1)

Arm I

EXPERIMENTAL

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.

Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: diagnostic laboratory biomarker analysis; Other: pharmacological study; Drug: dexamethasone

Interventions

gamma-secretase/Notch signalling pathway inhibitor RO4929097 DRUG

Given PO

Also known as: R4733, RO4929097

Arm I

diagnostic laboratory biomarker analysis OTHER

Correlative studies

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

dexamethasone DRUG

Given IV

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Arm I

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed malignancy (at diagnosis or relapse)
• Biopsy not required for intrinsic brain stem tumors or optic pathway gliomas
• No B-cell precursor acute lymphoblastic lymphoma (ALL) or acute myeloid leukemia
• No T-cell leukemia with CNS3 disease
• Measurable or evaluable 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
• Neurologic deficits in patients with CNS tumors must have been relatively stable for 1 week
• No active CNS leukemia
• Karnofsky performance status (PS) 50-100% (for patients \> 16 years of age) or Lansky PS 50-100% (for patients ≤ 16 years of age)
• Patients who are unable to walk because of paralysis,but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the PS
• Patients with solid tumors without bone marrow involvement must meet the following criteria:
• Peripheral ANC ≥ 1,000/mm\^3
• Platelet count ≥ 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions within the past 7 days)
• Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
• Patients with known bone marrow metastatic disease must meet the above criteria and must not be known to be refractory to red cell or platelet transfusion

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (12)

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Stanford University Hospitals and Clinics

Stanford, California, 94305, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Rhabdoid Tumor; Choroid Plexus Neoplasms; Oligodendroglioma; Adenoma, Basophil; Adenoma, Chromophobe; Adenoma, Acidophil; Prolactinoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large-Cell, Anaplastic; Astrocytoma; Familial ependymoma; Dendritic Cell Sarcoma, Interdigitating; Medulloblastoma; Burkitt Lymphoma; Spinal Cord Neoplasms; Optic Nerve Glioma; Pituitary Neoplasms; Recurrence; Leukemia, Large Granular Lymphocytic

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; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Cerebral Ventricle Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Adenoma; Endocrine Gland Neoplasms; Pituitary Diseases; Hypothalamic Diseases; Endocrine System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Histiocytic Disorders, Malignant; Histiocytosis; Neuroectodermal Tumors, Primitive; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Spinal Cord Diseases; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, T-Cell

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Najat Daw

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 16, 2010
• First Posted: March 17, 2010
• Study Start: March 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: November 5, 2014

Record last verified: 2011-10

Locations

US (11); CA (1)