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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: 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

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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. 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).

II. 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.

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

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

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

SECONDARY OBJECTIVES:

I. 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.

II. 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]).

III. 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 m
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • 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) [ Time Frame: 28 days ]
  • MTD of RO4929097 administered with dexamethasone determined according to DLTs graded using CTCAE v4.0 [ Time Frame: 28 days ]


Original Primary Outcome:

  • Maximum-tolerated dose (MTD) and recommended phase II dose of gamma-secretase inhibitor RO4929097 with or without dexamethasone
  • Toxicities associated with gamma-secretase inhibitor RO4929097 with or without dexamethasone
  • Pharmacokinetics


Current Secondary Outcome: Antitumor activity of RO4929097 with or without dexamethasone assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 30 days ]

Original Secondary Outcome: Antitumor activity of gamma-secretase inhibitor RO4929097 with or without dexamethasone

Information By: National Cancer Institute (NCI)

Dates:
Date Received: March 16, 2010
Date Started: March 2010
Date Completion:
Last Updated: November 4, 2014
Last Verified: October 2011