TGR-1202 Alone and in Combination With Either Nab-paclitaxel + Gemcitabine or With FOLFOX in Patients With Select Relapsed or Refractory Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1 multi-center study to assess the safety and efficacy of TGR-1202 as a single agent or in combination with nab-paclitaxel + gemcitabine or with FOLFOX in patients with select relapsed or refractory solid tumors.

Detailed Description
-----------------
TGR-1202 will be evaluated alone or in combination with nab-paclitaxel + gemcitabine or with FOLFOX in patients with adenocarcinoma of the pancreas, adenocarcinoma of the colon, rectum, gastric and GE junction cancer, and GI Stromal Tumor (GIST) who have relapsed from or are refractory to prior treatment.

Official Title
-----------------
A Phase I Study Evaluating the Safety and Efficacy of TGR 1202 Alone and in Combination With Either Nab-paclitaxel + Gemcitabine or With FOLFOX in Patients With Select Relapsed or Refractory Solid Tumors

Conditions
-----------------
Pancreatic Cancer, Colorectal Cancer, Rectal Cancer, Gastric Cancer, Esophageal Cancer, Gastrointestinal Stromal Tumor (GIST)

Intervention / Treatment
-----------------
* Drug: TGR-1202
* Drug: nab-paclitaxel + gemcitabine
* Drug: Oxaliplatin + Folinic acid + Fluorouracil
* Drug: Oxaliplatin + Folinic acid + Fluorouracil + Bevacizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed: adenocarcinoma of the pancreas (pancreatic cancer) adenocarcinoma of the colon or rectum (colorectal cancer) adenocarcinoma of the gastric (gastric cancer) esophageal cancer gastrointestinal stromal tumor (GIST) Relapsed or refractory disease Measurable lesion by RECIST 1.1 Exclusion Criteria: Known Hepatitis B, C or HIV infection Previous therapy with any drug that inhibits the PI3K pathway Anti-tumor therapy within 21 days of study Day 1

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TGR-1202<br>TGR-1202 daily dose | Drug: TGR-1202<br>* TGR-1202 oral daily dose<br>|
| Experimental: TGR-1202 + nab-paclitaxel + gemcitabine<br>TGR-1202 oral daily dose + nab-paclitaxel + gemcitabine both as an IV infusion | Drug: TGR-1202<br>* TGR-1202 oral daily dose<br>Drug: nab-paclitaxel + gemcitabine<br>* IV infusion<br>* Other names: Abraxane (nab-paclitaxel) + Gemzar (gemcitabine);|
| Experimental: TGR-1202 + FOLFOX<br>TGR-1202 oral daily dose + oxaliplatin IV infusion + leucovorin IV infusion followed by 5-fluorouracil IV bolus followed by 5-FU IV infusion (FOLFOX regimen) | Drug: TGR-1202<br>* TGR-1202 oral daily dose<br>Drug: Oxaliplatin + Folinic acid + Fluorouracil<br>* IV infusion<br>* Other names: Eloxatin (Oxaliplatin) + Leucovorin (Folinic acid) + 5-FU (Fluorouracil);|
| Experimental: TGR-1202 + FOLFOX + Bevacizumab<br>TGR-1202 oral daily dose + oxaliplatin IV infusion + leucovorin IV infusion followed by 5-fluorouracil IV bolus followed by 5-FU IV infusion (FOLFOX regimen) + bevacizumab IV infusion | Drug: TGR-1202<br>* TGR-1202 oral daily dose<br>Drug: Oxaliplatin + Folinic acid + Fluorouracil + Bevacizumab<br>* IV Infusion<br>* Other names: Eloxatin (Oxaliplatin) + Leucovorin (Folinic acid) + 5-FU (Fluorouracil) + Avastin (Bevacizumab);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events as a measure of safety and tolerability of TGR-1202 as a single agent and in combination in combination with nab-paclitaxel + gemcitabine, or with oxaliplatin + leucovorin + 5-FU (FOLFOX) or with FOLFOX + bevacizumab. | To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities. | Up to 28 days after the last patient enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate with TGR-1202 as a single agent and in combination with nab-paclitaxel + gemcitabine, or with oxaliplatin + leucovorin + 5-FU (FOLFOX) or with FOLFOX + bevacizumab. | Up to 1 year | 
| Duration of Response | Duration of response with TGR-1202 as a single agent and in combination with nab-paclitaxel + gemcitabine, or with oxaliplatin + leucovorin + 5-FU (FOLFOX) or with FOLFOX + bevacizumab. | Up to 1 year | 
| Pharmacokinetic (PK) profile of TGR-1202. Peak Plasma Concentration (Cmax). | This endpoint will measure the plasma PK profile of TGR-1202 as a single agent and in combination with nab-paclitaxel + gemcitabine, or with oxaliplatin + leucovorin + 5-FU (FOLFOX) or with FOLFOX + bevacizumab. | At selected timepoints up through 6 months | 
| Pharmacokinetic (PK) profile of TGR-1202. Time to Peak Plasma Concentration (Tmax). |  | At selected timepoints up through 6 months | 
| Pharmacokinetic (PK) profile of TGR-1202. Area under the plasma concentration versus time curve (AUC) |  | At selected timepoints up through 6 months |