Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer

Phase 1

Terminated

Brief Summary: This is a multicenter, open-label, Phase 1, dose escalation trial to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of TH-302 in combination with gemcitabine and nab-paclitaxel in previously untreated subjects with locally advanced unresectable or metastatic pancreatic adenocarcinoma.

Recruitment & Eligibility

Inclusion Criteria

Subjects greater than or equal to (>=) 18 years of age with locally advanced unresectable or metastatic pancreatic adenocarcinoma proven by histology or cytology and previously untreated with chemotherapy or systemic therapy other than:
- Radiosensitizing doses of 5-fluorouracil;
- Radiosensitizing doses of gemcitabine if relapse occurred at least 6 months after completion of gemcitabine;
- Neoadjuvant chemotherapy if relapse occurred at least 6 months after surgical resection;
- Adjuvant chemotherapy if relapse occurred at least 6 months after completion of adjuvant chemotherapy
Subjects may have measurable or non-measurable disease according to RECIST 1.1.
Eastern cooperative oncology group (ECOG) performance status of 0 or 1
Acceptable hematological status, liver and renal function as defined in the protocol
Other protocol defined inclusion criteria could apply

Exclusion Criteria

Significant cardiac or peripheral vascular arterial disease
Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months)
Severe chronic obstructive or other pulmonary disease with hypoxemia
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Subjects receiving concomitant treatment with radiotherapy or other investigational drugs
Other protocol defined exclusion criteria could apply

Arm && Interventions

Group	Intervention	Description
TH-302 plus Nab-paclitaxel plus Gemcitabine	TH-302	-
TH-302 plus Nab-paclitaxel plus Gemcitabine	Nab-paclitaxel	-
TH-302 plus Nab-paclitaxel plus Gemcitabine	Gemcitabine	-

Primary Outcome Measures

Name	Time	Method
Number of Subjects Experiencing Dose Limiting Toxicity (DLT)	Up to Day 28 of Cycle 1

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria	Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria	Baseline and 8 weeks after Day 1 of Cycle 1
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	Baseline up to Day 30 after the last dose of study treatment
Duration of Overall Response According to RECIST Version 1.1 Criteria	Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Progression Free Survival (PFS) Time	Time from enrollment to progressive disease (PD) or occurrence of death due to any cause within 120 days of either first administration of study drug or the last tumor assessment
Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria	Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment

Locations (5): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Washington University
🇺🇸
Saint Louis, Missouri, United States
Mayo Clinic
🇺🇸
Scottsdale, Arizona, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States