Clinical Trial: Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

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

Official Title: Phase II Study of RO4929097 (NSC-749225) in Advanced Melanoma

Brief Summary: This phase II trial is studying how well gamma-secretase/Notch signalling pathway inhibitor RO4929097 works in treating patients with stage IV melanoma. Gamma-secretase/Notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the six-month progression-free survival and one-year overall survival probability in Stage IV melanoma patients treated with RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097).

SECONDARY OBJECTIVES:

I. To investigate in a preliminary manner the relationship between Notch activation status and gene expression profile of tumor and clinical outcomes from patients in this study.

II. To study the effects of the investigational therapy on T cell function, which will provide a basis for subsequent trials combining Notch blockade with immunomodulatory therapy for advanced melanoma.

III. To assess the response rate (confirmed and unconfirmed complete and partial responses).

IV. To assess toxicity.

OUTLINE: This is a multicenter study.

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 orally (PO) on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood collection at baseline and during study for analysis of T-cell function by flow cytometry and ELISA. Tumor tissue samples from biopsy or surgery are also analyzed for Notch activation by IHC and qRT-PCR.

After completion of study therapy, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Progression-free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Disease assessments were performed every 6 weeks, up to 3 years. ]
    From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.
  • Overall Survival [ Time Frame: Weekly, up to 3 years. ]
    From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.


Original Primary Outcome:

  • 6-month progression-free survival
  • 1-year overall survival


Current Secondary Outcome:

  • Percentage of Participants With Confirmed and Unconfirmed Complete or Partial Response [ Time Frame: Disease assessments for response were performed every 6 weeks, up to 3 years ]
    Complete disappearance of all measurable and non-measurable disease, or greater than or equal to 30% decrease under baseline of the sum of the longest diameters of all target measurable lesions.
  • Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [ Time Frame: Toxicity assessment was evaluated at least every 3 weeks at the beginning of each cycle, up to 3 years ]
    Adverse Events (AEs) are reported by CTCAE version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.


Original Secondary Outcome:

  • Relationship between Notch activation status, gene expression profile, and clinical outcomes
  • RO4929097 effects on T-cell function
  • Response rate (confirmed and unconfirmed complete or partial response)
  • Toxicity


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 7, 2010
Date Started: October 2010
Date Completion:
Last Updated: May 6, 2016
Last Verified: May 2016