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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02047500
• Other study ID #: EMR200592-006
• Status: Terminated
• Phase: Phase 1
• First received: January 24, 2014
• Last updated: July 18, 2017
• Start date: January 2014
• Est. completion date: May 2016

Study information

• Verified date: July 2017
• Source: Threshold Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: May 2016
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• TH-302
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.
• Nab-paclitaxel
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.
• Gemcitabine
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.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Threshold Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects Experiencing Dose Limiting Toxicity (DLT)		Up to Day 28 of Cycle 1
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)		Baseline up to Day 30 after the last dose of study treatment