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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pancreatic Cancer
Interventions Drug: TH-302
Drug: Nab-paclitaxel
Drug: Gemcitabine
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title TH-302 Plus Nab-paclitaxel Plus Gemcitabine
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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.

Period Title: Overall Study
Started 19
Completed 0
Not Completed 19
Arm/Group Title TH-302 Plus Nab-paclitaxel Plus Gemcitabine
Hide Arm/Group Description

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.

Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
<=18 years
0
   0.0%
Between 18 and 65 years
11
  57.9%
>=65 years
8
  42.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
10
  52.6%
Male
9
  47.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants
19
1.Primary Outcome
Title Number of Subjects Experiencing Dose Limiting Toxicity (DLT)
Hide Description [Not Specified]
Time Frame Up to Day 28 of Cycle 1
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Hide Analysis Population Description
One patient not evaluable as they did not complete cycle 1
Arm/Group Title TH-302 Plus Nab-paclitaxel Plus Gemcitabine
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 18
Measure Type: Count of Participants
Unit of Measure: Participants
1
   5.6%
2.Secondary Outcome
Title Progression Free Survival (PFS) Time
Hide Description [Not Specified]
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
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria
Hide Description [Not Specified]
Time Frame Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Duration of Overall Response According to RECIST Version 1.1 Criteria
Hide Description [Not Specified]
Time Frame Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria
Hide Description [Not Specified]
Time Frame Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria
Hide Description [Not Specified]
Time Frame Baseline and 8 weeks after Day 1 of Cycle 1
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Hide Description [Not Specified]
Time Frame Baseline up to Day 30 after the last dose of study treatment
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TH-302 Plus Nab-paclitaxel Plus Gemcitabine
Hide Arm/Group Description

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.

All-Cause Mortality
TH-302 Plus Nab-paclitaxel Plus Gemcitabine
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
TH-302 Plus Nab-paclitaxel Plus Gemcitabine
Affected / at Risk (%) # Events
Total   19/19 (100.00%)    
Blood and lymphatic system disorders   
Febrile neutropenia   1/19 (5.26%)  1
Pancytopenia   2/19 (10.53%)  2
Cardiac disorders   
Cardiac failure congestive   1/19 (5.26%)  3
Gastrointestinal disorders   
Abdominal pain   1/19 (5.26%)  1
Retroperitoneal haemorrhage   1/19 (5.26%)  1
General disorders   
Chest pain   1/19 (5.26%)  1
Pyrexia   1/19 (5.26%)  1
Hepatobiliary disorders   
Bile duct obstruction   1/19 (5.26%)  1
Cholangitis   1/19 (5.26%)  1
Cholangitis acute   1/19 (5.26%)  2
Infections and infestations   
Cellulitis of male external genital organ   1/19 (5.26%)  1
Pneumonia   2/19 (10.53%)  3
Sepsis   3/19 (15.79%)  3
Urinary tract infection   1/19 (5.26%)  1
Metabolism and nutrition disorders   
Hypokalaemia   1/19 (5.26%)  1
Nervous system disorders   
Presyncope   1/19 (5.26%)  1
Syncope   1/19 (5.26%)  1
Renal and urinary disorders   
Acute kidney injury   1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders   
Lung infiltration   1/19 (5.26%)  1
Respiratory failure   1/19 (5.26%)  1
Skin and subcutaneous tissue disorders   
Rash erythematous   1/19 (5.26%)  1
Vascular disorders   
Hypotension   1/19 (5.26%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TH-302 Plus Nab-paclitaxel Plus Gemcitabine
Affected / at Risk (%) # Events
Total   19/19 (100.00%)    
Blood and lymphatic system disorders   
Anaemia   13/19 (68.42%)  57
Leukopenia   8/19 (42.11%)  132
Neutropenia   14/19 (73.68%)  88
Pancytopenia   2/19 (10.53%)  2
Thrombocytopenia   15/19 (78.95%)  99
Ear and labyrinth disorders   
Tinnitus   2/19 (10.53%)  2
Gastrointestinal disorders   
Abdominal pain   7/19 (36.84%)  10
Abdominal pain lower   2/19 (10.53%)  3
Abdominal pain upper   3/19 (15.79%)  4
Constipation   8/19 (42.11%)  10
Diarrhoea   9/19 (47.37%)  12
Flatulence   2/19 (10.53%)  5
Nausea   13/19 (68.42%)  20
Proctalgia   3/19 (15.79%)  3
Stomatitis   6/19 (31.58%)  7
Vomiting   9/19 (47.37%)  17
General disorders   
Chills   8/19 (42.11%)  13
Fatigue   14/19 (73.68%)  27
Infusion site rash   2/19 (10.53%)  2
Mucosal inflammation   2/19 (10.53%)  2
Non-cardiac chest pain   3/19 (15.79%)  3
Oedema peripheral   8/19 (42.11%)  12
Pyrexia   7/19 (36.84%)  12
Hepatobiliary disorders   
Bile duct obstruction   2/19 (10.53%)  2
Hyperbilirubinaemia   2/19 (10.53%)  2
Infections and infestations   
Oral herpes   2/19 (10.53%)  3
Investigations   
Neutrophil count decreased   3/19 (15.79%)  11
Weight decreased   6/19 (31.58%)  11
White blood cell count decreased   2/19 (10.53%)  2
Metabolism and nutrition disorders   
Decreased appetite   9/19 (47.37%)  14
Dehydration   3/19 (15.79%)  6
Hyperglycaemia   2/19 (10.53%)  3
Hypokalaemia   4/19 (21.05%)  6
Hypomagnesaemia   2/19 (10.53%)  2
Hypophosphataemia   2/19 (10.53%)  5
Musculoskeletal and connective tissue disorders   
Arthralgia   3/19 (15.79%)  6
Back pain   2/19 (10.53%)  2
Muscle spasms   2/19 (10.53%)  2
Muscular weakness   2/19 (10.53%)  2
Myalgia   5/19 (26.32%)  5
Pain in extremity   3/19 (15.79%)  4
Nervous system disorders   
Dizziness   4/19 (21.05%)  4
Dysgeusia   3/19 (15.79%)  3
Headache   4/19 (21.05%)  4
Peripheral sensory neuropathy   9/19 (47.37%)  21
Psychiatric disorders   
Anxiety   2/19 (10.53%)  2
Depression   2/19 (10.53%)  2
Insomnia   4/19 (21.05%)  4
Renal and urinary disorders   
Pollakiuria   2/19 (10.53%)  2
Respiratory, thoracic and mediastinal disorders   
Cough   6/19 (31.58%)  10
Dyspnoea   5/19 (26.32%)  6
Dyspnoea exertional   2/19 (10.53%)  2
Epistaxis   4/19 (21.05%)  4
Oropharyngeal pain   3/19 (15.79%)  3
Skin and subcutaneous tissue disorders   
Alopecia   12/19 (63.16%)  15
Erythema   2/19 (10.53%)  2
Pruritus   2/19 (10.53%)  2
Rash   10/19 (52.63%)  22
Rash maculo-papular   2/19 (10.53%)  2
Vascular disorders   
Flushing   3/19 (15.79%)  6
Hot flush   2/19 (10.53%)  3
Hypotension   3/19 (15.79%)  4
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Thomas Wilson
Organization: Threshold Pharmaceuticals
Phone: 302-359-0565
EMail: twilson@thresholdpharm.com
Layout table for additonal information
Responsible Party: Threshold Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02047500    
Other Study ID Numbers: EMR200592-006
First Submitted: January 24, 2014
First Posted: January 28, 2014
Results First Submitted: July 18, 2017
Results First Posted: December 15, 2017
Last Update Posted: December 15, 2017