Back to resultsPhase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer
Primary Purpose
Pancreatic Cancer
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TH-302
Nab-paclitaxel
Gemcitabine
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring TH-302, Nab-paclitaxel, Gemcitabine, Evofosfamide
Eligibility Criteria
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
Sites / Locations
- Mayo Clinic
- Massachusetts General Hospital
- Dana Farber Cancer Institute
- Washington University
- Fox Chase Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TH-302 plus Nab-paclitaxel plus Gemcitabine
Arm Description
Outcomes
Primary Outcome Measures
Number of Subjects Experiencing Dose Limiting Toxicity (DLT)
Secondary Outcome Measures
Progression Free Survival (PFS) Time
Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria
Duration of Overall Response According to RECIST Version 1.1 Criteria
Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria
Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Full Information
NCT ID
NCT02047500
First Posted
January 24, 2014
Last Updated
July 18, 2017
Sponsor
Threshold Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02047500
Brief Title
Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Terminated
Why Stopped
The trial has been terminated earlier following the company decision to discontinue the clinical development of Evofosfamide
Study Start Date
January 2014 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
May 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Threshold Pharmaceuticals
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
TH-302, Nab-paclitaxel, Gemcitabine, Evofosfamide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TH-302 plus Nab-paclitaxel plus Gemcitabine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
TH-302
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Subjects Experiencing Dose Limiting Toxicity (DLT)
Time Frame
Up to Day 28 of Cycle 1
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) Time
Time Frame
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
Title
Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria
Time Frame
Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Title
Duration of Overall Response According to RECIST Version 1.1 Criteria
Time Frame
Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Title
Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria
Time Frame
Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Title
Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria
Time Frame
Baseline and 8 weeks after Day 1 of Cycle 1
Title
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Time Frame
Baseline up to Day 30 after the last dose of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25679067
Citation
Sun JD, Liu Q, Ahluwalia D, Li W, Meng F, Wang Y, Bhupathi D, Ruprell AS, Hart CP. Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer. Cancer Biol Ther. 2015;16(3):438-49. doi: 10.1080/15384047.2014.1003005.
Results Reference
derived
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Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer
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