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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Phase I Dose Escalation Trial of TH-302 in Combination With Gemcitabine and Nab-Paclitaxel in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: TH-302
* Drug: Nab-paclitaxel
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TH-302 plus Nab-paclitaxel plus Gemcitabine<br> | Drug: TH-302<br>* TH-302 will be administered at a dose ranging from 170-340 milligram per square meter (mg/m^2) as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.<br>Drug: Nab-paclitaxel<br>* Nab-paclitaxel will be administered at a dose ranging from 100-125 mg/m^2 as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.<br>Drug: Gemcitabine<br>* Gemcitabine will be administered at a dose ranging from 800-1000 mg/m^2 as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing Dose Limiting Toxicity (DLT) |  | Up to Day 28 of Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TH-302, Nab-paclitaxel, Gemcitabine, Evofosfamide