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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by EMD Serono
Sponsor:
Collaborator:
Threshold Pharmaceuticals
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT02047500
First received: January 24, 2014
Last updated: May 2, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Drug: TH-302
Drug: Nab-paclitaxel
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Number of subjects experiencing dose limiting toxicity (DLT) [ Time Frame: Up to Day 28 of Cycle 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of subjects with Treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline up to Day 30 after the last dose of study treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 48
Study Start Date: January 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TH-302 plus Nab-paclitaxel plus Gemcitabine 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02047500

Contacts
Contact: US Medical Information 888-275-7376

Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations    507-538-7623      
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States
United States, Missouri
Washington University Recruiting
St Louis, Missouri, United States
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
EMD Serono
Threshold Pharmaceuticals
Investigators
Study Director: Medical Responsible EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT02047500     History of Changes
Other Study ID Numbers: EMR200592-006
Study First Received: January 24, 2014
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
TH-302
Nab-paclitaxel
Gemcitabine

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 18, 2014