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The trial has been terminated earlier following the company decision to discontinue the clinical development of Evofosfamide
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| Name | Class |
|---|---|
| Threshold Pharmaceuticals | INDUSTRY |
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TH-302 plus Nab-paclitaxel plus Gemcitabine | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TH-302 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Experiencing Dose Limiting Toxicity (DLT) | Up to Day 28 of Cycle 1 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Scottsdale | Arizona | 85259 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25679067 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | TH-302 Plus Nab-paclitaxel Plus Gemcitabine | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | TH-302 Plus Nab-paclitaxel Plus Gemcitabine | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects Experiencing Dose Limiting Toxicity (DLT) | One patient not evaluable as they did not complete cycle 1 | Posted | Count of Participants | Participants | Up to Day 28 of Cycle 1 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TH-302 Plus Nab-paclitaxel Plus Gemcitabine | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis of male external genital organ | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oral herpes | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Wilson | Threshold Pharmaceuticals | 302-359-0565 | twilson@thresholdpharm.com |
Not provided
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
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| ID | Term |
|---|---|
| C552526 | TH 302 |
| C520255 | 130-nm albumin-bound paclitaxel |
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| Nab-paclitaxel | Drug | 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 | Drug | 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. |
|
| 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 | 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 | 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 | Baseline and 8 weeks after Day 1 of Cycle 1 |
| Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 30 after the last dose of study treatment |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Washington University | St Louis | Missouri | 63110 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Progression Free Survival (PFS) Time | Not Posted | 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 | Participants |
| Secondary | Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria | Not Posted | Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment | Participants |
| Secondary | Duration of Overall Response According to RECIST Version 1.1 Criteria | Not Posted | Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment | Participants |
| Secondary | Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria | Not Posted | Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment | Participants |
| Secondary | Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria | Not Posted | Baseline and 8 weeks after Day 1 of Cycle 1 | Participants |
| Secondary | Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | Not Posted | Baseline up to Day 30 after the last dose of study treatment | Participants |
| 19 |
| 19 |
| 19 |
| 19 |
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Presyncope | Nervous system disorders | Systematic Assessment |
|
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Cardiac failure congestive | Cardiac disorders | Systematic Assessment |
|
| Hypotension | Vascular disorders | Systematic Assessment |
|
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Retroperitoneal haemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | Systematic Assessment |
|
| Cholangitis acute | Hepatobiliary disorders | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
|
| Chest pain | General disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | Systematic Assessment |
|
| Flushing | Vascular disorders | Systematic Assessment |
|
| Hot flush | Vascular disorders | Systematic Assessment |
|
| Hypotension | Vascular disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Infusion site rash | General disorders | Systematic Assessment |
|
| Mucosal inflammation | General disorders | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | Systematic Assessment |
|
| Oedema peripheral | General disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Weight decreased | Investigations | Systematic Assessment |
|
| White blood cell count decreased | Investigations | Systematic Assessment |
|
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| D004066 |
| Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |