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

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ClinicalTrials.gov Identifier: NCT02047500
Recruitment Status : Terminated (The trial has been terminated earlier following the company decision to discontinue the clinical development of Evofosfamide)
First Posted : January 28, 2014
Results First Posted : December 15, 2017
Last Update Posted : December 15, 2017
Sponsor:
Information provided by (Responsible Party):
Threshold Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE January 24, 2014
First Posted Date  ICMJE January 28, 2014
Results First Submitted Date  ICMJE July 18, 2017
Results First Posted Date  ICMJE December 15, 2017
Last Update Posted Date December 15, 2017
Study Start Date  ICMJE January 2014
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2017)
Number of Subjects Experiencing Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 of Cycle 1 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 24, 2014)
Number of subjects experiencing dose limiting toxicity (DLT) [ Time Frame: Up to Day 28 of Cycle 1 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2017)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Day 30 after the last dose of study treatment ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2014)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Number of subjects with Treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline up to Day 30 after the last dose of study treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • 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.
  • Drug: 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.
  • Drug: 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.
Study Arms  ICMJE Experimental: TH-302 plus Nab-paclitaxel plus Gemcitabine
Interventions:
  • Drug: TH-302
  • Drug: Nab-paclitaxel
  • Drug: Gemcitabine
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 29, 2016)
19
Original Estimated Enrollment  ICMJE
 (submitted: January 24, 2014)
48
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02047500
Other Study ID Numbers  ICMJE EMR200592-006
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Threshold Pharmaceuticals
Original Responsible Party EMD Serono
Current Study Sponsor  ICMJE Threshold Pharmaceuticals
Original Study Sponsor  ICMJE EMD Serono
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Responsible EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
PRS Account Threshold Pharmaceuticals
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP