Trial Outcomes & Findings for Phase II Trial of Nab-Paclitaxel and Gemcitabine for First-Line Treatment of Patients With Cholangiocarcinoma (NCT NCT02181634)

NCT ID: NCT02181634

Last Updated: 2018-10-03

Results Overview

Progression-free survival is defined as the time from the date of first study treatment to either the date of documented disease progression or death from any cause, whichever occurred first. Progression-free survival rate at 6 months is defined as the proportion of patients who were disease progression-free and alive at 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameter/axes of target lesions, taking as reference the smallest sum on study, or unequivocal progression of existing non-target lesions, or the appearance of new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 74 participants
• Primary outcome timeframe: Assessed at 6 months
• Results posted on: 2018-10-03

Participant Flow

Participant milestones

Measure	Nab-Paclitaxel and Gemcitabine Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.
Overall Study STARTED	74
Overall Study Eligible and Treated	73
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	72

Reasons for withdrawal

Measure	Nab-Paclitaxel and Gemcitabine Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.
Overall Study Lack of Efficacy	33
Overall Study Adverse Event	17
Overall Study Physician Decision	8
Overall Study Withdrawal by Subject	5
Overall Study Death	2
Overall Study Treatment delayed greater than 4 weeks	3
Overall Study Ineligible	1
Overall Study Max number of dose reduction	1
Overall Study Symptomatic progression	1
Overall Study Patient opted to proceed to surgery	1

Baseline Characteristics

Phase II Trial of Nab-Paclitaxel and Gemcitabine for First-Line Treatment of Patients With Cholangiocarcinoma

Baseline characteristics by cohort

Measure	Nab-Paclitaxel and Gemcitabine n=73 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	71 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	67 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed at 6 months

Population: Eligible and treated

Progression-free survival is defined as the time from the date of first study treatment to either the date of documented disease progression or death from any cause, whichever occurred first. Progression-free survival rate at 6 months is defined as the proportion of patients who were disease progression-free and alive at 6 months.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the diameter/axes of target lesions, taking as reference the smallest sum on study, or unequivocal progression of existing non-target lesions, or the appearance of new lesions.

Outcome measures

Measure

Nab-Paclitaxel and Gemcitabine n=73 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.

Progression-Free Survival (PFS) Rate at 6 Months (Proportion of Participants Alive and Progression-Free at 6 Months)

0.605 proportion of participants Interval 0.482 to 0.729

SECONDARY outcome

Timeframe: Every 3-6 months for up to 3 years

Population: Eligible and treated

OS is defined as the time from enrollment until death or last patient contact.

Outcome measures

Measure

Nab-Paclitaxel and Gemcitabine n=73 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.

Overall Survival (OS)

11.2 months Interval 9.6 to 14.7

SECONDARY outcome

Timeframe: Every 3-6 months for up to 3 years

Population: Eligible and treated patients

Progression-free survival is defined as the time from the date of first study treatment to either the date of documented disease progression or death from any cause, whichever occurred first.

Outcome measures

Measure

Nab-Paclitaxel and Gemcitabine n=73 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.

Progression-free Survival (PFS)

7.7 months Interval 5.9 to 13.1

SECONDARY outcome

Timeframe: Every 3-6 months for up to 3 years

Population: Eligible and treated

TTP was defined as the time from date of first dose of study therapy to date of removal from study for progression. Patients who have not experienced progression were censored at the date of last disease evaluation. Progression is evaluated using Solid Tumor Response Criteria (RECIST) Version 1.1. Progression is defined as at least a 20% increase in the sum of the diameters/axes of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm over the nadir. The appearance of new lesions or unequivocal progression of existing non-target lesions also constitutes disease progression.

Outcome measures

Measure

Nab-Paclitaxel and Gemcitabine n=73 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.

Time To Progression (TTP)

7.7 months Interval 6.5 to 13.1

SECONDARY outcome

Timeframe: Every 3-6 months for up to 3 years

Population: Eligible and treated

Overall response rate is defined as the proportion of patients with complete response or partial response per RECIST version 1.1. Complete response is defined as disappearance of all lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters/axes of target lesions and the persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker levels above the normal limits. A confirmation assessment performed >=4 weeks after the criteria for response is met is required.

Outcome measures

Measure

Nab-Paclitaxel and Gemcitabine n=73 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.

Overall Response Rate (ORR)

0.301 proportion of participants Interval 0.199 to 0.42

SECONDARY outcome

Timeframe: Every 3-6 months for up to 3 years

Population: Eligible and treated patients

Disease control rate is the proportion of patients achieved complete response, partial response or stable disease per RECIST version 1.1. Complete response is defined as disappearance of all lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters/axes of target lesions and the persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker levels above the normal limits. Stable disease is defined as neither sufficient shrinkage to qualify for complete or partial response nor sufficient increase to qualify for progression. A confirmation assessment performed >=4 weeks after the criteria for response is met is required.

Outcome measures

Measure

Nab-Paclitaxel and Gemcitabine n=73 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.

Disease Control Rate (DCR)

0.658 proportion of participants Interval 0.537 to 0.765

SECONDARY outcome

Timeframe: CA 19-9 was evaluated every 8 weeks until progression or for up to 3 years and off-treatment

Population: Eligible and treated patients with CA 19-9 data available

Patients were dichotomized into maximum CA 19-9 decline >=50% and maximum CA 19-9 decline <50%. Cox proportional hazards model was used to evaluate the association between PFS and maximum change in CA 19-9.

Outcome measures

Measure	Nab-Paclitaxel and Gemcitabine n=35 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.
Association Between PFS and Maximum Change in Carbohydrate Antigen (CA) 19-9 From Baseline CA 19-9 decline >=50%	7.7 months Interval 6.6 to 13.1
Association Between PFS and Maximum Change in Carbohydrate Antigen (CA) 19-9 From Baseline CA 19-9 decline <50%	1.9 months Interval 1.6 to 18.2

SECONDARY outcome

Timeframe: CA 19-9 was evaluated every 8 weeks until progression or for up to 3 years and off-treatment

Population: Eligible and treated patients with CA 19-9 data available

Patients were dichotomized into maximum CA 19-9 decline >=50% and maximum CA 19-9 decline <50%. Cox proportional hazards model was used to evaluate the association between OS and maximum change in CA 19-9.

Outcome measures

Measure	Nab-Paclitaxel and Gemcitabine n=35 Participants Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.
Association Between OS and Maximum Change in Carbohydrate Antigen (CA) 19-9 From Baseline CA 19-9 decline >=50%	14.6 months Interval 10.2 to 25.6
Association Between OS and Maximum Change in Carbohydrate Antigen (CA) 19-9 From Baseline CA 19-9 decline <50%	10.2 months Interval 4.1 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

OTHER_PRE_SPECIFIED outcome

Timeframe: Prior to Cycle 1, Day 1; Cycle 1 Day 8; Cycle 3, Day 1 and at Off Treatment

Correlate change in CTCs to median PFS, OS, TTP, ORR and DCR.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Correlate stromal SPARC (high versus low) expression by immunohistochemistry (IHC) with median PFS, OS, TTP, ORR and DCR.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Correlate fibrosis (low, intermediate and high) by trichrome staining with median PFS, OS, TTP, ORR and DCR.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Correlate CDA (high versus low) expression by IHC with median PFS, OS, TTP, ORR and DCR.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Correlate hENT1 (high versus low) expression by IHC with median PFS, OS, TTP, ORR and DCR.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Prior to Cycle 1, Day 1; Cycle 1, Day 8; Cycle 3, Day 1 and at Off Treatment

Optional specimen banking of patient blood specimens (including serum, plasma and buffy coat) as well as fixed left-over tissue specimens when available from all enrolled patients in this trial for possible future molecular, pharmacogenomic, and/or proteomic testing.

Outcome measures

Outcome data not reported

Adverse Events

Nab-Paclitaxel and Gemcitabine

Serious events: 42 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Measure	Nab-Paclitaxel and Gemcitabine n=74 participants at risk Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.
Blood and lymphatic system disorders Anemia	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Blood and lymphatic system disorders Febrile neutropenia	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Blood and lymphatic system disorders Haemolytic uraemic syndrome	4.1% 3/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Blood and lymphatic system disorders Neutropenia	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Cardiac disorders Atrial fibrillation	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Cardiac disorders Cardiac failure	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Cardiac disorders Cardiac failure congestive	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Cardiac disorders Pericardial effusion	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Cardiac disorders Tachycardia	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Abdominal pain	4.1% 3/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Ascites	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Constipation	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Diarrhea	4.1% 3/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Gastrointestinal haemorrhage	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Disease progression	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Fatigue	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Generalised oedema	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Multi-organ failure	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Oedema peripheral	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Pyrexia	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Hepatobiliary disorders Bile duct obstruction	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Hepatobiliary disorders Bile duct stenosis	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Hepatobiliary disorders Biliary fistula	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Hepatobiliary disorders Cholangitis	4.1% 3/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Hepatobiliary disorders Cholecystitis	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Hepatobiliary disorders Cholestasis	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Hepatobiliary disorders Hyperbilirubinaemia	4.1% 3/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Abscess	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Biliary tract infection	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Clostridium difficile infection	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Device related infection	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Diverticulitis	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Emphysematous cholecystitis	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Infection	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Lung infection	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Neutropenic sepsis	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Pneumonia	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Sepsis	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Injury, poisoning and procedural complications Humerus fracture	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Injury, poisoning and procedural complications Post procedural haemorrhage	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Neutrophil count decreased	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Metabolism and nutrition disorders Hyponatraemia	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Metabolism and nutrition disorders Hypovolaemia	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Encephalopathy	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Facial nerve disorder	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Haemorrhage intracranial	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Headache	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Hepatic encephalopathy	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Syncope	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Renal and urinary disorders Acute kidney injury	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Renal and urinary disorders Renal failure	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.7% 2/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Skin and subcutaneous tissue disorders Rash macular	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Skin and subcutaneous tissue disorders Rash maculo-papular	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Deep vein thrombosis	4.1% 3/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Embolism	4.1% 3/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Hypertension	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Hypotension	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Thrombosis	1.4% 1/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy

Other adverse events

Measure	Nab-Paclitaxel and Gemcitabine n=74 participants at risk Nab-Paclitaxel 125 mg/m² IV and Gemcitabine 1000 mg/m² on days 1, 8 and 15 every 28 days until progression or unacceptable toxicity. Nab-Paclitaxel and Gemcitabine: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.
Gastrointestinal disorders Abdominal distension	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Abdominal pain	16.2% 12/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Renal and urinary disorders Acute kidney injury	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Alanine aminotransferase increased	24.3% 18/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Skin and subcutaneous tissue disorders Alopecia	52.7% 39/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Blood and lymphatic system disorders Anemia	41.9% 31/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Musculoskeletal and connective tissue disorders Arthralgia	17.6% 13/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Ascites	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Aspartate aminotransferase increased	24.3% 18/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Asthenia	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Musculoskeletal and connective tissue disorders Back pain	8.1% 6/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Blood alkaline phosphatase increased	23.0% 17/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Blood bilirubin increased	9.5% 7/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Musculoskeletal and connective tissue disorders Bone pain	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Chills	14.9% 11/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Constipation	45.9% 34/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Cough	14.9% 11/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Decreased appetite	37.8% 28/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Deep vein thrombosis	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Metabolism and nutrition disorders Dehydration	9.5% 7/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Diarrhea	47.3% 35/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Dizziness	14.9% 11/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Dry mouth	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Dysgeusia	23.0% 17/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Dyspnea	29.7% 22/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Embolism	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Epistaxis	14.9% 11/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Fatigue	71.6% 53/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Headache	8.1% 6/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Hot flashes	8.1% 6/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Hyperbilirubinemia	9.5% 7/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Vascular disorders Hypertension	13.5% 10/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Hypoalbuminemia	12.2% 9/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Hypocalcemia	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Metabolism and nutrition disorders Hypokalaemia	9.5% 7/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Metabolism and nutrition disorders Hyponatremia	10.8% 8/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Influenza like illness	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Psychiatric disorders Insomnia	16.2% 12/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Leukopenia	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Mucosal inflammation	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Musculoskeletal and connective tissue disorders Muscular weakness	18.9% 14/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Musculoskeletal and connective tissue disorders Myalgia	10.8% 8/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Skin and subcutaneous tissue disorders Nail discolouration	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Nausea	45.9% 34/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Neuropathy peripheral	37.8% 28/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Blood and lymphatic system disorders Neutropenia	35.1% 26/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Neutrophil count decreased	18.9% 14/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Oedema peripheral	41.9% 31/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Pain	9.5% 7/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Musculoskeletal and connective tissue disorders Pain in extremity	12.2% 9/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Peripheral sensory neuropathy	12.2% 9/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Platelet count decreased	14.9% 11/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Skin and subcutaneous tissue disorders Pruritus	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
General disorders Pyrexia	24.3% 18/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Skin and subcutaneous tissue disorders Rash	12.2% 9/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Skin and subcutaneous tissue disorders Rash maculo-papular	9.5% 7/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Infections and infestations Sepsis	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Stomatitis	10.8% 8/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Thrombocytopenia	21.6% 16/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Nervous system disorders Tremor	5.4% 4/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Eye disorders Vision blurred	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Gastrointestinal disorders Vomiting	24.3% 18/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Weight decreased	29.7% 22/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations Weight increased	6.8% 5/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy
Investigations White blood cell count decreased	13.5% 10/74 • Assessed every week for the first 2 cycles, then every two cycles (every 8 weeks) and 30 days after the last dose of therapy

Additional Information

PrECOG Statistician

ECOG-ACRIN Biostatistics Center

Phone: 617-632-3633

Email: pcata@jimmy.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place