LDE225 + Everolimus in Advanced Gastroesophageal Adenocarcinoma
|ClinicalTrials.gov Identifier: NCT02138929|
Recruitment Status : Completed
First Posted : May 15, 2014
Last Update Posted : June 11, 2020
|Condition or disease||Intervention/treatment||Phase|
|Esophageal Cancer||Drug: Everolimus Drug: LDE 225||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of LDE225 in Combination With Everolimus in Patients With Advanced Gastroesophageal Adenocarcinoma|
|Actual Study Start Date :||November 10, 2014|
|Actual Primary Completion Date :||June 8, 2020|
|Actual Study Completion Date :||June 8, 2020|
Experimental: Everolimus + LDE 225
Dose Escalation: Everolimus at a dose of 10 mg by mouth daily with dose escalation of LDE 225 from 200 mg - 800mg by mouth daily. Study cycle is 28 days.
Dose Expansion: Everolimus at a dose of 10 mg by mouth daily. LDE 225 at MTD from Dose Escalation. Study cycle is 28 days.
Induction and Dose Expansion Phase: 10 mg by mouth daily in a 28 day cycle.
Drug: LDE 225
Induction Phase Starting Dose: 400 mg by mouth daily in a 28 day cycle.
Expansion Phase Starting Dose: Maximum tolerated dose from Induction Phase.
- Maximum Tolerated Dose (MTD) of LDE225 in Combination with Everolimus in Participants with Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction (GEJ) or Stomach in the Second or Third Line Setting [ Time Frame: 10 weeks ]Maximum tolerated dose (MTD) defined as highest dose level for the combination therapy with no more than 1 out of 6 patients experiencing dose limiting toxicity (DLT). DLT defined as an adverse event (AE) or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤56 days following the first dose of LDE225 (DLT assessment period).
- Safety of LDE225 in Combination with Everolimus in a Cohort of Participants with Metastatic Nuclear Gli-1 Expressing Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach per CTCAE. [ Time Frame: 30 days after last dose of study drug given. ]A Bayesian method by Thall, Simon, and Estey  used for safety monitoring, starting from the 5th patient. The monitoring rule for toxicity is Pr (P(Tox) > 0.25 | data) > 0.80, where P(Tox) is the proportion of patients that experience DLT and it has a prior distribution of beta (0.5, 1.5).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02138929
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jaffer Ajani, MD||M.D. Anderson Cancer Center|