Trial Outcomes & Findings for A Study Comparing CO-1.01 With Gemcitabine as First Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma (LEAP) (NCT NCT01124786)

NCT ID: NCT01124786

Last Updated: 2014-04-17

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 367 participants
• Primary outcome timeframe: Monthly follow up after treatment discontinuation until death, up to 1.5 years.
• Results posted on: 2014-04-17

Participant Flow

This was a multicenter, multinational study conducted at 98 medical centers in Europe, Australia, and the Americas. The first patient was randomized on 04-Aug-2010 and the last patient on 09-April-2012.

Eligible patients were randomized (1:1) to receive either gemcitabine elaidate or gemcitabine. The stratification factors in this model were Eastern Cooperative Group Performance Status (ECOG PS) (0 vs 1) and region (North America/Western Europe/Australia vs Eastern Europe vs South America).

Participant milestones

Measure	CO-1.01 CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Overall Study STARTED	182	185
Overall Study Intent-to-Treat (ITT) Population	182	185
Overall Study Safety Population	179	181
Overall Study Tumor Evaluable Population	178	180
Overall Study COMPLETED	178	180
Overall Study NOT COMPLETED	4	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study Comparing CO-1.01 With Gemcitabine as First Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma (LEAP)

Baseline characteristics by cohort

Measure	Gemcitabine Elaidate n=182 Participants CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine n=185 Participants Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks	Total n=367 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	103 Participants n=5 Participants	116 Participants n=7 Participants	219 Participants n=5 Participants
Age, Categorical >=65 years	79 Participants n=5 Participants	69 Participants n=7 Participants	148 Participants n=5 Participants
Age, Continuous	62.5 years STANDARD_DEVIATION 9.62 • n=5 Participants	60.5 years STANDARD_DEVIATION 11.19 • n=7 Participants	61.5 years STANDARD_DEVIATION 10.47 • n=5 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	74 Participants n=7 Participants	148 Participants n=5 Participants
Sex: Female, Male Male	108 Participants n=5 Participants	111 Participants n=7 Participants	219 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants	22 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Ukraine	40 participants n=5 Participants	47 participants n=7 Participants	87 participants n=5 Participants
Region of Enrollment Russian Federation	45 participants n=5 Participants	40 participants n=7 Participants	85 participants n=5 Participants
Region of Enrollment Italy	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment United Kingdom	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment France	19 participants n=5 Participants	10 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Canada	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Argentina	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Brazil	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Belgium	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Australia	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Germany	14 participants n=5 Participants	17 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment Norway	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Sweden	1 participants n=5 Participants	7 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Monthly follow up after treatment discontinuation until death, up to 1.5 years.

Population: Analysis was per protocol and included hENT-1 low Intent to Treat (IIT) population.

Outcome measures

Measure	CO-1.01 n=114 Participants CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine n=118 Participants Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Overall Survival in Patients With Low High Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression	5.7 months Interval 4.7 to 7.6	6.1 months Interval 5.2 to 7.7

SECONDARY outcome

Timeframe: Monthly follow up after treatment discontinuation until death, up to 1.5 years

Population: Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 8 weeks

Population: Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 4 weeks, up to 1.5 years

Population: Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every week, up to 1.5 years

Population: Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 4 weeks, up to 1.5 years

Population: Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 4 weeks, up to 1.5 years

Population: Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 30 days after first dose

Population: Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Outcome measures

Outcome data not reported

Adverse Events

CO-1.01

Serious events: 82 serious events

Other events: 171 other events

Deaths: 0 deaths

Gemcitabine

Serious events: 82 serious events

Other events: 164 other events

Deaths: 0 deaths

Serious adverse events

Measure	CO-1.01 n=179 participants at risk CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine n=181 participants at risk Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Blood and lymphatic system disorders Anaemia	3.4% 6/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.7% 3/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Blood and lymphatic system disorders Leukopenia	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Blood and lymphatic system disorders Thrombocytopenia	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Cardiac disorders Acute myocardial infarction	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Cardiac disorders Atrial fibrillation	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Cardiac disorders Cardiac failure	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Cardiac disorders Cardiac failure acute	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Cardiac disorders Cardiovascular disorder	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Abdominal pain	1.7% 3/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Abdominal pain upper	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Ascites	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Colitis	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Constipation	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Duodenal obstruction	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Duodenal stenosis	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Enteritis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Erosive oesophagitis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Asthenia	1.7% 3/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Device occlusion	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Fatigue	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Oedema peripheral	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Pyrexia	1.7% 3/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.7% 3/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Sudden cardiac death	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Sudden death	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Bile duct obstruction	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Cholangitis	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	2.2% 4/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Cholestasis	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	3.3% 6/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Jaundice	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Jaundice cholestatic	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Biliary sepsis	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	2.2% 4/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Biliary tract infection	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Bronchitis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Bronchopneumonia	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Cellulitis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Device related infection	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Enterococcal bacteraemia	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Erysipelas	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Escherichia urinary tract infection	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Infection	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Liver abscess	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Lobar pneumonia	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Lymphangitis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Nasopharyngitis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Peritonitis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Peritonitis bacterial	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Pneuomococcal sepsis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Pneumonia	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	2.2% 4/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Sepsis	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Urinary tract infection	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Injury, poisoning and procedural complications Infusion related reaction	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Injury, poisoning and procedural complications Intestinal anastomosis complication	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Injury, poisoning and procedural complications Pneuomothorax traumatic	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Alanine aminotransferase increased	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Aspartate aminotransferase increased	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Blood alkaline phosphatase increased	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Blood bilirubin increased	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	2.8% 5/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations C-reactive protein increased	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Haemoglobin decreased	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Platelet count decreased	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Decreased appetite	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Dehydration	2.8% 5/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Fluid retention	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Hypercalcaemia	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Hyperglycaemia	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Hyperkalaemia	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Hyperuricaemia	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Hyponatraemia	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Malnutrition	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Musculoskeletal and connective tissue disorders Back pain	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	17.9% 32/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	21.5% 39/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Cerebrovascular accident	1.7% 3/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Convulsion	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Dizziness	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Haemorrhage intracranial	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Hypotonia	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Ischaemic stroke	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Syncope	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Renal and urinary disorders Acute prerenal failure	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Renal and urinary disorders Hydronephrosis	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Renal and urinary disorders Prerenal failure	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Renal and urinary disorders Renal failure acute	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Renal and urinary disorders Urinary retention	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Couth	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.7% 3/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.2% 4/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	2.8% 5/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Vascular disorders Arterial thrombosis limb	5.0% 9/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.7% 3/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Vascular disorders Deep vein thrombosis	1.7% 3/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Vascular disorders Hypertension	1.7% 3/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Vascular disorders Thrombophlebitis	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Vascular disorders Venous thrombosis limb	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Gastric haemorrhage	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Gastric stenosis	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Gastric ulcer	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Intestinal obstruction	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Mallory-Weiss syndrome	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Nausea	1.7% 3/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Obstruction gastric	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Pancreatitis	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Pancreatitis acute	0.56% 1/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.00% 0/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Vomiting	2.2% 4/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.7% 3/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Dilatation intrahepatic duct acquired	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	1.1% 2/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Renal and urinary disorders Renal failure	1.1% 2/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Infection (not confirmed) due to fever and elevated CRP	0.00% 0/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.

Other adverse events

Measure	CO-1.01 n=179 participants at risk CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine n=181 participants at risk Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Gastrointestinal disorders Nausea	39.1% 70/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	32.6% 59/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Blood and lymphatic system disorders Anaemia	36.3% 65/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	43.1% 78/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Blood and lymphatic system disorders Thrombocytopenia	29.6% 53/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	33.1% 60/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Asthenia	26.3% 47/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	18.8% 34/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Blood and lymphatic system disorders Neutropenia	25.7% 46/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	26.0% 47/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Decreased appetite	23.5% 42/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	18.2% 33/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Vomiting	22.9% 41/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	19.3% 35/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Fatigue	21.2% 38/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	24.9% 45/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Pyrexia	19.6% 35/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	22.7% 41/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Diarrhoea	19.0% 34/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	16.6% 30/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Abdominal pain	17.9% 32/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	13.3% 24/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Constipation	14.5% 26/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	13.8% 25/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
General disorders Oedema peripheral	14.0% 25/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	18.8% 34/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Alanine aminotransferase increased	11.2% 20/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	8.3% 15/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Abdominal pain upper	10.6% 19/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	16.0% 29/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.1% 18/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	13.3% 24/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Aspartate aminotransferase increased	8.9% 16/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	10.5% 19/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Blood and lymphatic system disorders Platelet count decreased	7.8% 14/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	5.5% 10/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Weight decreased	7.8% 14/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	5.5% 10/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Musculoskeletal and connective tissue disorders Back pain	7.3% 13/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	8.8% 16/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Psychiatric disorders Insomnia	7.3% 13/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	5.5% 10/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 12/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	3.9% 7/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Blood and lymphatic system disorders Leukopenia	6.7% 12/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	9.4% 17/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Blood akaline phosphatase increased	6.1% 11/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	5.5% 10/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Dizziness	6.1% 11/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	4.4% 8/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Nervous system disorders Headache	6.1% 11/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	6.6% 12/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Hepatobiliary disorders Hyperbilirubinaemia	6.1% 11/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	9.4% 17/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Blood and lymphatic system disorders Thrombocytosis	5.6% 10/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	0.55% 1/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Investigations Gamma-glutamyltransferase increased	5.0% 9/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	4.4% 8/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Gastrointestinal disorders Ascites	3.9% 7/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	9.4% 17/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Vascular disorders Hypertension	3.9% 7/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	5.5% 10/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Vascular disorders Hypotension	2.8% 5/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	5.5% 10/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Infections and infestations Urinary tract infection	2.8% 5/179 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.	6.1% 11/181 • Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.

Additional Information

VP Clinical Development

Clovis Oncology, Inc.

Phone: 415-409-5440

Email: clinicaltrialinfo@clovisoncology.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 120 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER