Study of Minnelide™ in Patients With Advanced GI Tumors
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Minnelide™ Given Daily for 21 Days Followed by 7 Days Off Schedule in Patients With Advanced GI Tumors.|
- To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of Minnelide™ [ Time Frame: 24 months ]The MTD will be determined using a 3 + 3 design and will continue until 2 patients at any dose level experience a DLT. A DLT will be defined as Grade 4 neutropenia lasting ≥ 5 days or Grade 3 or 4 neutropenia with fever and/or infection;Grade 4 thrombocytopenia (or Grade 3 with bleeding);Grade 3 or 4 treatment-related non-hematological toxicity (Grade 3 nausea, vomiting or diarrhea that last > 72 hours despite maximal treatment constitutes a DLT, insufficient treatment will not constitute an exception to the DLT criteria, as this would constitute inadequate conduct of the study); Dosing delay greater than 2 weeks due to treatment-emergent AEs or related severe laboratory abnormalities.
- To establish the dose of Minnelide™ recommended for future phase 2 protocol [ Time Frame: 24 months ]Once the MTD has been determined this will be the dose going forward in phase 2 studies
- To determine the pharmacokinetics of Minnelide™ [ Time Frame: 24 months ]
Plasma concentration data will be used to determine the following PK parameters:
- AUC Area under the concentration curve
- Cmax Maximum plasma concentration
- Tmax Time to maximum plasma concentration
- t1/2 Terminal phase half life
- CL/F Total body clearance
- Vd/F Apparent volume of distribution
- To observe patients for any evidence of antitumor activity of Minnelide™ per RECIST criteria [ Time Frame: 24 months ]Objective measurements of tumor size will be recorded from PET, CT scan and other measures.
- To determine pharmacodynamic effect of Minnelide™ on HSP70 levels. And to explore pharmacodynamics effect of Minnelide™ on PET Scans and using Choi criteria on the CT scans. [ Time Frame: 24 months ]
As part of exploratory PD, the following assessments will be performed:
- Biomarkers including CA19-9 (or CA125, CEA if non-secretors for pancreas cancer), CEA and CA125 as applicable, any tumor marker appropriate to the given cancer or that is known to be elevated in a given patient will be evaluated according the Investigator's discretion, prior to every Cycle.
- Serum HSP70 levels
- PET Scans
- Evaluation of CT scans using Choi criteria
|Study Start Date:||August 2013|
|Study Completion Date:||December 2016|
|Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Experimental: Minnelide™ 001
A Phase 1, Multi-Center, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™ given daily for 21 days followed by 7 days off schedule in patients with Advanced GI Tumors
Drug: Minnelide™ 001
Minnelide™ will be given as a single agent intravenously as a 30-minute infusion daily x 21 days followed by a 7-day rest period. One cycle will equal 28 days.
Other Name: Minnelide
This is a Phase 1, open label, multicenter, dose-escalation study of safety, pharmacokinetics, and pharmacodynamics of Minnelide™
Minnelide™ will be given as a single agent intravenously as a 30-minute infusion daily x 21 days followed by a 7-day rest period. One cycle will equal 28 days. Dose escalation will follow a modified Fibonacci design.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01927965
|United States, Arizona|
|Virginia G. Piper Cancer Center at Scottsdale Healthcare|
|Scottsdale, Arizona, United States, 85258|
|United States, Minnesota|
|University of Minnesota Masonic Cancer Clinic|
|Minneapolis, Minnesota, United States, 55455|
|Study Director:||Mohana Velagapudi, MD||Minneamrita Therapeutics LLC|
|Study Director:||Linda Vocila, BSN||TD2|