Trial Outcomes & Findings for Clinical Trial Testing TH-302 in Combination With Gemcitabine in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma (NCT NCT01746979)
NCT ID: NCT01746979
Last Updated: 2025-05-11
Results Overview
Overall survival is defined as time from randomization to death or last day known to be alive.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
693 participants
Primary outcome timeframe
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Results posted on
2025-05-11
Participant Flow
Participant milestones
| Measure |
Gemcitabine Plus TH-302
TH-302: TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
Gemcitabine Plus Placebo
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Placebo (5 percent dextrose - D5W): TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
|---|---|---|
|
Overall Study
STARTED
|
346
|
347
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
346
|
347
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Clinical Trial Testing TH-302 in Combination With Gemcitabine in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
Baseline characteristics by cohort
| Measure |
Gemcitabine Plus TH-302
n=346 Participants
TH-302: TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
Gemcitabine Plus Placebo
n=347 Participants
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Placebo (5 percent dextrose - D5W): TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
Total
n=693 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65 years
STANDARD_DEVIATION 9.70 • n=99 Participants
|
63.8 years
STANDARD_DEVIATION 9.82 • n=107 Participants
|
64.4 years
STANDARD_DEVIATION 9.77 • n=206 Participants
|
|
Sex: Female, Male
Female
|
155 Participants
n=99 Participants
|
168 Participants
n=107 Participants
|
323 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
191 Participants
n=99 Participants
|
179 Participants
n=107 Participants
|
370 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 yearsOverall survival is defined as time from randomization to death or last day known to be alive.
Outcome measures
| Measure |
Gemcitabine Plus TH-302
n=346 Participants
TH-302: TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
Gemcitabine Plus Placebo
n=347 Participants
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Placebo (5 percent dextrose - D5W): TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
|---|---|---|
|
Overall Survival
|
8.9 months
Interval 7.6 to 9.9
|
7.6 months
Interval 6.7 to 8.3
|
SECONDARY outcome
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 yearsProgression Free Survival is defined as the time from randomization to either first observation of progressive disease or occurrence of death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Gemcitabine Plus TH-302
n=346 Participants
TH-302: TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
Gemcitabine Plus Placebo
n=347 Participants
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Placebo (5 percent dextrose - D5W): TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
|---|---|---|
|
Progression Free Survival
|
5.5 months
Interval 4.8 to 5.6
|
3.7 months
Interval 3.6 to 3.8
|
Adverse Events
TH-302
Serious events: 341 serious events
Other events: 341 other events
Deaths: 0 deaths
Placebo
Serious events: 338 serious events
Other events: 338 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TH-302
n=341 participants at risk
TH-302: TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
Placebo
n=338 participants at risk
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Placebo (5 percent dextrose - D5W): TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
|---|---|---|
|
Infections and infestations
Appendicitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/341
|
0.59%
2/338 • Number of events 3
|
|
Infections and infestations
Bacterial infection
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Bacterial prostatitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Biliary sepsis
|
0.88%
3/341 • Number of events 3
|
0.59%
2/338 • Number of events 2
|
|
Infections and infestations
Biliary tract infection
|
0.59%
2/341 • Number of events 3
|
0.00%
0/338
|
|
Infections and infestations
Bronchopneumonia
|
0.59%
2/341 • Number of events 2
|
0.00%
0/338
|
|
Infections and infestations
Cellulitis
|
0.88%
3/341 • Number of events 3
|
0.59%
2/338 • Number of events 2
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Cystitis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Device related infection
|
1.2%
4/341 • Number of events 5
|
0.59%
2/338 • Number of events 2
|
|
Infections and infestations
Device related sepsis
|
0.59%
2/341 • Number of events 2
|
0.00%
0/338
|
|
Infections and infestations
Diabetic gangrene
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Diverticulitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Enterococcal infection
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Erysipelas
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Escherichia infection
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Escherichia sepsis
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Febrile infection
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Fungal oesophagitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Herpes zoster
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Infection
|
0.59%
2/341 • Number of events 2
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Infusion site infection
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Klebsiella bacteraemia
|
0.00%
0/341
|
0.30%
1/338 • Number of events 2
|
|
Infections and infestations
Klebsiella sepsis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/341
|
0.30%
1/338 • Number of events 2
|
|
Infections and infestations
Meningoencephalitis herpetic
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Oesophageal candidiasis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Oropharyngeal candidiasis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Pancreatic abscess
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Penile infection
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Peritonitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Pharyngitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Pneumonia
|
2.6%
9/341 • Number of events 11
|
2.4%
8/338 • Number of events 8
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Sepsis
|
1.5%
5/341 • Number of events 5
|
1.5%
5/338 • Number of events 5
|
|
Infections and infestations
Septic shock
|
0.29%
1/341 • Number of events 1
|
0.59%
2/338 • Number of events 2
|
|
Infections and infestations
Splenic abscess
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Infections and infestations
Subcutaneous abscess
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Urinary tract infection
|
1.2%
4/341 • Number of events 4
|
0.00%
0/338
|
|
Infections and infestations
Urosepsis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.59%
2/341 • Number of events 3
|
0.59%
2/338 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant ascites
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Paraneoplastic syndrome
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Blood and lymphatic system disorders
Anaemia
|
4.4%
15/341 • Number of events 18
|
4.7%
16/338 • Number of events 18
|
|
Blood and lymphatic system disorders
Bone marrow failure
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.29%
1/341 • Number of events 1
|
1.8%
6/338 • Number of events 7
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.29%
1/341 • Number of events 1
|
2.7%
9/338 • Number of events 13
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Blood and lymphatic system disorders
Splenic infarction
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Blood and lymphatic system disorders
Splenic vein thrombosis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/341
|
5.6%
19/338 • Number of events 25
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Metabolism and nutrition disorders
Cachexia
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.59%
2/341 • Number of events 2
|
0.59%
2/338 • Number of events 2
|
|
Metabolism and nutrition disorders
Dehydration
|
0.59%
2/341 • Number of events 2
|
0.59%
2/338 • Number of events 2
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.59%
2/341 • Number of events 2
|
0.59%
2/338 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.59%
2/341 • Number of events 2
|
0.00%
0/338
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.59%
2/341 • Number of events 2
|
0.30%
1/338 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Metabolism and nutrition disorders
Metabolic disorder
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Psychiatric disorders
Anxiety
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Psychiatric disorders
Confusional state
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Psychiatric disorders
Depression
|
0.59%
2/341 • Number of events 3
|
0.30%
1/338 • Number of events 1
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Nervous system disorders
Amnesia
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Nervous system disorders
Balance disorder
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Nervous system disorders
Cerebral artery stenosis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Nervous system disorders
Cerebral infarction
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/341
|
0.89%
3/338 • Number of events 3
|
|
Nervous system disorders
Coma
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Nervous system disorders
Convulsion
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.29%
1/341 • Number of events 2
|
0.00%
0/338
|
|
Nervous system disorders
Headache
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Nervous system disorders
Hemianopia
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Nervous system disorders
Ischaemic stroke
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Nervous system disorders
Transient ischaemic attack
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Eye disorders
Macular hole
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Cardiac disorders
Acute myocardial infarction
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
Cardiac disorders
Aortic valve disease
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Cardiac disorders
Atrial fibrillation
|
0.88%
3/341 • Number of events 3
|
0.00%
0/338
|
|
Cardiac disorders
Atrial tachycardia
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 2
|
|
Cardiac disorders
Cardiac arrest
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Cardiac disorders
Cardiac failure
|
0.88%
3/341 • Number of events 3
|
0.00%
0/338
|
|
Cardiac disorders
Cardiac failure congestive
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Vascular disorders
Aortic dissection
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Vascular disorders
Arterial occlusive disease
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Vascular disorders
Arterial thrombosis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Vascular disorders
Axillary vein thrombosis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Vascular disorders
Circulatory collapse
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Vascular disorders
Deep vein thrombosis
|
1.2%
4/341 • Number of events 4
|
2.1%
7/338 • Number of events 7
|
|
Vascular disorders
Embolism
|
0.88%
3/341 • Number of events 3
|
0.00%
0/338
|
|
Vascular disorders
Hypertension
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 2
|
|
Vascular disorders
Hypotension
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Vascular disorders
Peripheral ischaemia
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 2
|
|
Vascular disorders
Phlebitis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Vascular disorders
Shock haemorrhagic
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Vascular disorders
Thrombophlebitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Vascular disorders
Venous thrombosis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Acute interstitial pneumonitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.59%
2/341 • Number of events 2
|
0.59%
2/338 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.29%
1/341 • Number of events 1
|
0.59%
2/338 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.9%
10/341 • Number of events 10
|
3.3%
11/338 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
2.1%
7/341 • Number of events 8
|
3.0%
10/338 • Number of events 10
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.88%
3/341 • Number of events 3
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Ascites
|
1.5%
5/341 • Number of events 5
|
0.59%
2/338 • Number of events 2
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.88%
3/341 • Number of events 3
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.59%
2/341 • Number of events 2
|
2.4%
8/338 • Number of events 11
|
|
Gastrointestinal disorders
Duodenal obstruction
|
1.2%
4/341 • Number of events 4
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Duodenal perforation
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Duodenal stenosis
|
1.2%
4/341 • Number of events 4
|
0.89%
3/338 • Number of events 3
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Gastric perforation
|
0.59%
2/341 • Number of events 2
|
0.00%
0/338
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Gastric ulcer perforation
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.59%
2/341 • Number of events 2
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal inflammation
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
0.59%
2/341 • Number of events 2
|
0.00%
0/338
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Haematemesis
|
0.59%
2/341 • Number of events 2
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Ileus
|
0.88%
3/341 • Number of events 3
|
0.59%
2/338 • Number of events 2
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.88%
3/341 • Number of events 4
|
0.59%
2/338 • Number of events 2
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Intra-abdominal haemorrhage
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Nausea
|
1.2%
4/341 • Number of events 4
|
0.89%
3/338 • Number of events 4
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.88%
3/341 • Number of events 3
|
0.00%
0/338
|
|
Gastrointestinal disorders
Oedematous pancreatitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Pancreatitis
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 2
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.59%
2/341 • Number of events 2
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Gastrointestinal disorders
Subileus
|
0.88%
3/341 • Number of events 3
|
0.00%
0/338
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.59%
2/341 • Number of events 2
|
0.59%
2/338 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
3.8%
13/341 • Number of events 13
|
2.1%
7/338 • Number of events 8
|
|
Hepatobiliary disorders
Bile duct obstruction
|
1.8%
6/341 • Number of events 6
|
0.89%
3/338 • Number of events 3
|
|
Hepatobiliary disorders
Bile duct stenosis
|
1.5%
5/341 • Number of events 5
|
1.5%
5/338 • Number of events 5
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/341
|
0.30%
1/338 • Number of events 2
|
|
Hepatobiliary disorders
Biliary dilatation
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Hepatobiliary disorders
Cholangiectasis acquired
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Hepatobiliary disorders
Cholangiolitis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Hepatobiliary disorders
Cholangitis
|
4.4%
15/341 • Number of events 21
|
3.6%
12/338 • Number of events 12
|
|
Hepatobiliary disorders
Cholangitis acute
|
1.8%
6/341 • Number of events 10
|
0.30%
1/338 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
0.88%
3/341 • Number of events 3
|
0.59%
2/338 • Number of events 2
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
Hepatobiliary disorders
Cholestasis
|
0.59%
2/341 • Number of events 2
|
0.89%
3/338 • Number of events 3
|
|
Hepatobiliary disorders
Gallbladder obstruction
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Hepatobiliary disorders
Hepatic failure
|
0.29%
1/341 • Number of events 2
|
0.89%
3/338 • Number of events 3
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.29%
1/341 • Number of events 1
|
1.2%
4/338 • Number of events 4
|
|
Hepatobiliary disorders
Hepatorenal failure
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.59%
2/341 • Number of events 2
|
0.00%
0/338
|
|
Hepatobiliary disorders
Jaundice
|
1.2%
4/341 • Number of events 5
|
0.30%
1/338 • Number of events 1
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
1.8%
6/341 • Number of events 6
|
0.89%
3/338 • Number of events 3
|
|
Hepatobiliary disorders
Portal hypertension
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Diabetic foot
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin maceration
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Yellow skin
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.88%
3/341 • Number of events 3
|
0.89%
3/338 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Gouty arthritis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Renal and urinary disorders
Proteinuria
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Renal and urinary disorders
Renal failure
|
0.59%
2/341 • Number of events 2
|
0.59%
2/338 • Number of events 2
|
|
Renal and urinary disorders
Renal failure acute
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Renal and urinary disorders
Renal impairment
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Renal and urinary disorders
Urinary retention
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Congenital, familial and genetic disorders
Pyloric stenosis
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
General disorders
Asthenia
|
0.29%
1/341 • Number of events 1
|
1.2%
4/338 • Number of events 4
|
|
General disorders
Chills
|
0.59%
2/341 • Number of events 2
|
0.00%
0/338
|
|
General disorders
Device malfunction
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
General disorders
Device occlusion
|
0.00%
0/341
|
0.89%
3/338 • Number of events 3
|
|
General disorders
Disease progression
|
0.59%
2/341 • Number of events 2
|
1.2%
4/338 • Number of events 4
|
|
General disorders
Fatigue
|
0.88%
3/341 • Number of events 3
|
0.59%
2/338 • Number of events 2
|
|
General disorders
General physical health deterioration
|
4.1%
14/341 • Number of events 15
|
3.3%
11/338 • Number of events 12
|
|
General disorders
Generalised oedema
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
General disorders
Infusion site extravasation
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
General disorders
Injection site extravasation
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
General disorders
Local swelling
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
General disorders
Malaise
|
0.29%
1/341 • Number of events 1
|
0.59%
2/338 • Number of events 2
|
|
General disorders
Multi-organ failure
|
0.29%
1/341 • Number of events 2
|
0.30%
1/338 • Number of events 1
|
|
General disorders
Non-cardiac chest pain
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
General disorders
Oedema peripheral
|
0.29%
1/341 • Number of events 1
|
0.59%
2/338 • Number of events 2
|
|
General disorders
Pain
|
0.59%
2/341 • Number of events 2
|
0.00%
0/338
|
|
General disorders
Pyrexia
|
3.2%
11/341 • Number of events 12
|
4.1%
14/338 • Number of events 15
|
|
General disorders
Stent malfunction
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
General disorders
Sudden death
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Investigations
Blood bilirubin increased
|
0.88%
3/341 • Number of events 3
|
0.89%
3/338 • Number of events 3
|
|
Investigations
Blood creatinine increased
|
0.29%
1/341 • Number of events 1
|
0.30%
1/338 • Number of events 1
|
|
Investigations
Blood glucose fluctuation
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Investigations
C-reactive protein increased
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.59%
2/341 • Number of events 2
|
1.2%
4/338 • Number of events 4
|
|
Investigations
General physical condition abnormal
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Investigations
Liver function test abnormal
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/341
|
0.59%
2/338 • Number of events 2
|
|
Investigations
Platelet count decreased
|
0.59%
2/341 • Number of events 2
|
2.4%
8/338 • Number of events 8
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.29%
1/341 • Number of events 1
|
0.59%
2/338 • Number of events 5
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Injury, poisoning and procedural complications
Chemical peritonitis
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/341
|
0.30%
1/338 • Number of events 1
|
|
Injury, poisoning and procedural complications
Post procedural bile leak
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Injury, poisoning and procedural complications
Prescribed overdose
|
0.00%
0/341
|
0.30%
1/338 • Number of events 2
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
|
Injury, poisoning and procedural complications
Traumatic haemothorax
|
0.29%
1/341 • Number of events 1
|
0.00%
0/338
|
Other adverse events
| Measure |
TH-302
n=341 participants at risk
TH-302: TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
Placebo
n=338 participants at risk
Gemcitabine: Gemcitabine will be administered at a dose of 1000 (mg/m\^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Placebo (5 percent dextrose - D5W): TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
31.7%
108/341 • Number of events 254
|
48.5%
164/338 • Number of events 582
|
|
Blood and lymphatic system disorders
Leukopenia
|
8.5%
29/341 • Number of events 47
|
13.9%
47/338 • Number of events 198
|
|
Blood and lymphatic system disorders
Neutropenia
|
27.6%
94/341 • Number of events 248
|
41.4%
140/338 • Number of events 546
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
17.9%
61/341 • Number of events 151
|
46.7%
158/338 • Number of events 772
|
|
Metabolism and nutrition disorders
Decreased appetite
|
34.0%
116/341 • Number of events 184
|
34.6%
117/338 • Number of events 205
|
|
Nervous system disorders
Dysgeusia
|
9.7%
33/341 • Number of events 39
|
13.6%
46/338 • Number of events 57
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.9%
27/341 • Number of events 44
|
13.0%
44/338 • Number of events 55
|
|
Gastrointestinal disorders
Abdominal pain
|
20.5%
70/341 • Number of events 149
|
19.2%
65/338 • Number of events 110
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.1%
38/341 • Number of events 58
|
13.0%
44/338 • Number of events 66
|
|
Gastrointestinal disorders
Constipation
|
30.5%
104/341 • Number of events 146
|
30.8%
104/338 • Number of events 171
|
|
Gastrointestinal disorders
Diarrhoea
|
26.1%
89/341 • Number of events 181
|
33.1%
112/338 • Number of events 245
|
|
Gastrointestinal disorders
Nausea
|
44.0%
150/341 • Number of events 320
|
49.7%
168/338 • Number of events 354
|
|
Gastrointestinal disorders
Stomatitis
|
15.5%
53/341 • Number of events 78
|
25.4%
86/338 • Number of events 172
|
|
Gastrointestinal disorders
Vomiting
|
32.0%
109/341 • Number of events 233
|
32.2%
109/338 • Number of events 243
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.7%
23/341 • Number of events 30
|
20.1%
68/338 • Number of events 81
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.5%
46/341 • Number of events 65
|
18.6%
63/338 • Number of events 104
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.2%
45/341 • Number of events 58
|
8.9%
30/338 • Number of events 35
|
|
General disorders
Asthenia
|
20.8%
71/341 • Number of events 165
|
24.0%
81/338 • Number of events 229
|
|
General disorders
Fatigue
|
31.1%
106/341 • Number of events 219
|
29.0%
98/338 • Number of events 234
|
|
General disorders
Oedema peripheral
|
21.1%
72/341 • Number of events 104
|
18.9%
64/338 • Number of events 87
|
|
General disorders
Pyrexia
|
22.3%
76/341 • Number of events 147
|
18.9%
64/338 • Number of events 104
|
|
Investigations
Neutrophil count decreased
|
8.5%
29/341 • Number of events 94
|
15.4%
52/338 • Number of events 301
|
|
Investigations
Platelet count decreased
|
12.9%
44/341 • Number of events 122
|
29.6%
100/338 • Number of events 476
|
|
Investigations
White blood cell count decreased
|
8.2%
28/341 • Number of events 84
|
16.3%
55/338 • Number of events 263
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place