Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma
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|ClinicalTrials.gov Identifier: NCT01120275|
Recruitment Status : Terminated (Administratively complete.)
First Posted : May 10, 2010
Results First Posted : June 14, 2016
Last Update Posted : June 14, 2016
|Condition or disease||Intervention/treatment||Phase|
|Acral Lentiginous Malignant Melanoma Lentigo Maligna Malignant Melanoma Nodular Malignant Melanoma Recurrent Melanoma Solar Radiation-related Skin Melanoma Stage IV Melanoma Superficial Spreading Malignant Melanoma||Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097 Other: laboratory biomarker analysis||Phase 2|
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).
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of RO4929097 (NSC-749225) in Advanced Melanoma|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||May 2013|
|Actual Study Completion Date :||August 2015|
Experimental: Treatment (gamma-secretase inhibitor RO4929097)
Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Other: laboratory biomarker analysis
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01120275
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|Principal Investigator:||Kim Margolin||Southwest Oncology Group|