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

Phase 1

Completed

• Conditions: Gastrointestinal Stromal Tumor (GIST); Rectal Cancer; Colorectal Cancer; Gastric Cancer; Pancreatic Cancer; Esophageal Cancer
• Interventions: Drug: TGR-1202; Drug: Oxaliplatin + Folinic acid + Fluorouracil + Bevacizumab; Drug: nab-paclitaxel + gemcitabine; Drug: Oxaliplatin + Folinic acid + Fluorouracil

• Registration Number: NCT02574663
• Lead Sponsor: TG Therapeutics, Inc.

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.

Study Timeline

• Study Start: 2015-09-11
• Study First Submitted: 2015-10-01
• Study First Submitted QC: 2015-10-09
• Study First Posted: 2015-10-14
• Primary Completion: 2018-08
• Study Completion: 2018-08
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-01
• Last Update Posted: 2019-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

• Histologically confirmed:

  1. adenocarcinoma of the pancreas (pancreatic cancer)
  2. adenocarcinoma of the colon or rectum (colorectal cancer)
  3. adenocarcinoma of the gastric (gastric cancer)
  4. esophageal cancer
  5. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TGR-1202 + FOLFOX + Bevacizumab	Oxaliplatin + Folinic acid + Fluorouracil + Bevacizumab	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
TGR-1202 + nab-paclitaxel + gemcitabine	nab-paclitaxel + gemcitabine	TGR-1202 oral daily dose + nab-paclitaxel + gemcitabine both as an IV infusion
TGR-1202 + nab-paclitaxel + gemcitabine	TGR-1202	TGR-1202 oral daily dose + nab-paclitaxel + gemcitabine both as an IV infusion
TGR-1202	TGR-1202	TGR-1202 daily dose
TGR-1202 + FOLFOX	TGR-1202	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)
TGR-1202 + FOLFOX	Oxaliplatin + Folinic acid + Fluorouracil	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)
TGR-1202 + FOLFOX + Bevacizumab	TGR-1202	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

Primary Outcome Measures

Name	Time	Method
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.	Up to 28 days after the last patient enrolled	To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) profile of TGR-1202. Area under the plasma concentration versus time curve (AUC)	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
Duration of Response	Up to 1 year	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.
Pharmacokinetic (PK) profile of TGR-1202. Peak Plasma Concentration (Cmax).	At selected timepoints up through 6 months	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.
Overall Response Rate	Up to 1 year	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.

Trial Locations

Locations (1)

TG Therapeutics Trial Site; 🇺🇸 Nashville, Tennessee, United States