Trial Outcomes & Findings for Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers (NCT NCT03768414)

Last Updated: 2026-01-12

Results Overview

OS will be determined using the log-rank test with stratification by disease site (gallbladder adenocarcinoma versus \[vs.\] intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma), disease stage (locally advanced vs. metastatic), and Zubrod performance status (0 vs. 1). Distributions of overall survival by treatment arm will be estimated using the method of Kaplan-Meier.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

452 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2026-01-12

Participant Flow

452 participants were registered to the study, 10 were ineligible and 1 was not analyzable.

Participant milestones

Participant milestones
Measure	Gem+Cisplatin+Nab-paclitaxel Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	294	147
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	294	147

Reasons for withdrawal

Reasons for withdrawal
Measure	Gem+Cisplatin+Nab-paclitaxel Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study Adverse Event or side effects	72	28
Overall Study Refusal unrelated to adverse event	33	33
Overall Study Progression/relapse	132	60
Overall Study Death	9	6
Overall Study Other - not protocol specified	45	18
Overall Study Reason under review	3	2

Baseline Characteristics

Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gem+Cisplatin+Nab-paclitaxel n=294 Participants Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin n=147 Participants Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total n=441 Participants Total of all reporting groups
Age, Continuous	63.2 years n=210 Participants	63.9 years n=19 Participants	63.5 years n=8 Participants
Sex: Female, Male Female	162 Participants n=210 Participants	81 Participants n=19 Participants	243 Participants n=8 Participants
Sex: Female, Male Male	132 Participants n=210 Participants	66 Participants n=19 Participants	198 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	30 Participants n=210 Participants	15 Participants n=19 Participants	45 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	256 Participants n=210 Participants	125 Participants n=19 Participants	381 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=210 Participants	7 Participants n=19 Participants	15 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=210 Participants	1 Participants n=19 Participants	3 Participants n=8 Participants
Race (NIH/OMB) Asian	14 Participants n=210 Participants	7 Participants n=19 Participants	21 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=210 Participants	0 Participants n=19 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Black or African American	18 Participants n=210 Participants	7 Participants n=19 Participants	25 Participants n=8 Participants
Race (NIH/OMB) White	244 Participants n=210 Participants	119 Participants n=19 Participants	363 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=210 Participants	1 Participants n=19 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=210 Participants	12 Participants n=19 Participants	27 Participants n=8 Participants
Disease Site Gallbladder adenocarcinoma	46 Participants n=210 Participants	24 Participants n=19 Participants	70 Participants n=8 Participants
Disease Site Intrahepatic cholangiocarcinoma	198 Participants n=210 Participants	99 Participants n=19 Participants	297 Participants n=8 Participants
Disease Site Extrahepatic cholangiocarcinoma	50 Participants n=210 Participants	24 Participants n=19 Participants	74 Participants n=8 Participants
Disease Stage Locally advances	77 Participants n=210 Participants	41 Participants n=19 Participants	118 Participants n=8 Participants
Disease Stage Metastatic	217 Participants n=210 Participants	106 Participants n=19 Participants	323 Participants n=8 Participants
Performance Status 0	147 Participants n=210 Participants	75 Participants n=19 Participants	222 Participants n=8 Participants
Performance Status 1	147 Participants n=210 Participants	72 Participants n=19 Participants	219 Participants n=8 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Population: This population includes the 441 eligible and evaluable participants. 294 in the Gem+Cisplatin+Nab-paclitaxel arm and 147 in the Gemcitabine + Cisplatin arm.

Outcome measures

Outcome measures
Measure	Gem+Cisplatin+Nab-paclitaxel n=294 Participants Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin n=147 Participants Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS)	14.0 months Interval 12.4 to 16.1	13.6 months Interval 9.7 to 16.6

SECONDARY outcome

Timeframe: Duration of treatment and follow-up until death or 3 years post registration.

Population: Participants who were eligible and received at least one dose of protocol treatment.

Only adverse events that are possibly, probably, or definitely related to study drugs are reported. CTCAE Version 5.0 was used for all AE reporting.

Outcome measures

Outcome measures
Measure	Gem+Cisplatin+Nab-paclitaxel n=287 Participants Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin n=134 Participants Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Memory impairment	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Mucositis oral	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Multi-organ failure	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Muscle weakness lower limb	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Myalgia	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Nausea	11 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Neutrophil count decreased	105 Participants	37 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Pain	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Paresthesia	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Peripheral motor neuropathy	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Peripheral sensory neuropathy	10 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Peritoneal infection	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Platelet count decreased	56 Participants	20 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Pleural effusion	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Portal vein thrombosis	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Rectal hemorrhage	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Respiratory failure	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Respiratory, thoracic and mediastinal disorders -	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Seizure	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Sepsis	15 Participants	3 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Skin infection	4 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Superior vena cava syndrome	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Supraventricular tachycardia	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Syncope	2 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Thromboembolic event	9 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Thrush	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Typhlitis	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Upper gastrointestinal hemorrhage	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Urinary tract infection	4 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Vascular access complication	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Vasovagal reaction	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Vomiting	5 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Wheezing	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. White blood cell decreased	46 Participants	10 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Generalized muscle weakness	3 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Headache	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hearing impaired	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Heart failure	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hematuria	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hepatic infection	1 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hepatobiliary disorders - Other, specify	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hyperglycemia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hyperkalemia	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hypertension	7 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hypoalbuminemia	5 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hypocalcemia	3 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hypokalemia	9 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hypomagnesemia	6 Participants	5 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hyponatremia	6 Participants	4 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Hypotension	3 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Infections and infestations - Other, specify	3 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Infusion related reaction	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Investigations - Other, specify	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Lung infection	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Lymphocyte count decreased	30 Participants	4 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Alkaline phosphatase increased	3 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Anemia	95 Participants	30 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Anorexia	8 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Arthralgia	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Ascites	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Aspartate aminotransferase increased	5 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Ataxia	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Atrial fibrillation	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Back pain	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Blood and lymphatic system disorders - Other, spec	1 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Blood bilirubin increased	3 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Cardiac arrest	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Catheter related infection	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Cholecystitis	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Chronic kidney disease	2 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Colitis	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Constipation	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Creatinine increased	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Death NOS	1 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Dehydration	4 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Delirium	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Diarrhea	13 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Dizziness	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Dysphagia	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Dyspnea	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Edema limbs	4 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Endocarditis infective	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Enterocolitis	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Enterocolitis infectious	3 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Epistaxis	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Esophagitis	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Fatigue	27 Participants	8 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Febrile neutropenia	10 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Fever	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Flu like symptoms	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. GGT increased	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Gallbladder infection	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Gastric hemorrhage	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Gastrointestinal disorders - Other, specify	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. General disorders and administration site conditio	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Abdominal pain	2 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Acute kidney injury	5 Participants	3 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs. Alanine aminotransferase increased	6 Participants	1 Participants

SECONDARY outcome

Timeframe: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Population: This population includes the 441 eligible and evaluable participants. 294 in the Gem+Cisplatin+Nab-paclitaxel arm and 147 in the Gemcitabine + Cisplatin arm.

Distributions of PFS will be described using cumulative incidence estimates with differences in these estimates between treatment arms assessed by a stratified Cox regression model.

Outcome measures

Outcome measures
Measure	Gem+Cisplatin+Nab-paclitaxel n=294 Participants Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin n=147 Participants Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS)	7.5 months Interval 6.4 to 8.5	6.3 months Interval 4.4 to 8.2

SECONDARY outcome

Timeframe: Up to 3 years

ORR is defined as confirmed and unconfirmed; complete response + partial response + stable disease. The chi-square test will be used to compare ORR, disease control rate (DCR), and rates of toxicity events across arms. ORR will be assessed in the subset of patients with measurable disease.

Outcome measures

Outcome measures
Measure	Gem+Cisplatin+Nab-paclitaxel n=290 Participants Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin n=146 Participants Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria Complete Response	6 Participants	1 Participants
Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria Partial Response	55 Participants	11 Participants
Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria Unconfirmed Partial Response	30 Participants	19 Participants
Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria Stable/No Response	134 Participants	67 Participants
Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria Increasing Disease	38 Participants	22 Participants
Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria Symptomatic Deterioration	2 Participants	3 Participants
Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria Assessment Inadaquate	25 Participants	23 Participants

SECONDARY outcome

Timeframe: Up to 3 years

The chi-square test will be used to compare ORR, DCR, and rates of toxicity events across arms. Disease control includes confirmed and unconfirmed complete response, confirmed and unconfirmed partial response, and stable disease. In patients with non-measurable disease, disease control will be defined as those who are alive without disease progression.

Outcome measures

Outcome measures
Measure	Gem+Cisplatin+Nab-paclitaxel n=290 Participants Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin n=147 Participants Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Disease Control Rate as Measured by RECIST 1.1 Criteria	78 percentage of participants Interval 72.0 to 82.0	67 percentage of participants Interval 59.0 to 75.0

SECONDARY outcome

Timeframe: Baseline up to course 3

Population: one participant had missing baseline CA and 96 participants had missing post-treatment CA. They were not included in the analysis

Correlations between changes in CA19-9 levels from baseline to post-treatment and ORR will be estimated via logistic regression models, both within each treatment arm and in the overall cohort. Analyses will explore the prognostic and predictive values of CA19-9 for disease response.

Outcome measures

Outcome measures
Measure	Gem+Cisplatin+Nab-paclitaxel n=237 Participants Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Gemcitabine + Cisplatin n=102 Participants Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Changes in Carbohydrate Antigen 19-9 (CA 19-9) Levels	-12 U/mL Interval -151086.0 to 637797.0	-2.97 U/mL Interval -283830.0 to 3318.0

Adverse Events

Gemcitabine + Cisplatin

Serious events: 11 serious events

Other events: 133 other events

Deaths: 115 deaths

Gem+Cisplatin+Nab-paclitaxel

Serious events: 27 serious events

Other events: 280 other events

Deaths: 237 deaths

Serious adverse events

Other adverse events

Additional Information

Gastrointestinal Committee Statistician

SWOG Statistics and Data Management Center

Phone: 2066674623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Gemcitabine + Cisplatin n=134 participants at risk Patients receive cisplatin IV over 60 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. The number of participants at risk in All-cause Mortality are the number of participants included in the primary analysis.	Gem+Cisplatin+Nab-paclitaxel n=287 participants at risk Patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. The number of participants at risk in All-cause Mortality are the number of participants included in the primary analysis.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Infections and infestations Biliary tract infection	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.70% 2/287 • Duration of treatment and follow up until death or 3 years post registration.
Infections and infestations Infections and infestations-Other	0.75% 1/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Infections and infestations Sepsis	3.0% 4/134 • Duration of treatment and follow up until death or 3 years post registration.	2.1% 6/287 • Duration of treatment and follow up until death or 3 years post registration.
Investigations Alanine aminotransferase increased	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Investigations Alkaline phosphatase increased	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Investigations Aspartate aminotransferase increased	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Investigations Neutrophil count decreased	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	1.0% 3/287 • Duration of treatment and follow up until death or 3 years post registration.
Investigations Platelet count decreased	1.5% 2/134 • Duration of treatment and follow up until death or 3 years post registration.	1.0% 3/287 • Duration of treatment and follow up until death or 3 years post registration.
Investigations White blood cell decreased	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Metabolism and nutrition disorders Dehydration	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Metabolism and nutrition disorders Hypoglycemia	0.75% 1/134 • Duration of treatment and follow up until death or 3 years post registration.	0.00% 0/287 • Duration of treatment and follow up until death or 3 years post registration.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl	1.5% 2/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
General disorders Fatigue	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.70% 2/287 • Duration of treatment and follow up until death or 3 years post registration.
General disorders Multi-organ failure	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Blood and lymphatic system disorders Anemia	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.70% 2/287 • Duration of treatment and follow up until death or 3 years post registration.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	1.0% 3/287 • Duration of treatment and follow up until death or 3 years post registration.
Cardiac disorders Cardiac arrest	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Cardiac disorders Myocardial infarction	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Gastrointestinal disorders Abdominal distension	0.75% 1/134 • Duration of treatment and follow up until death or 3 years post registration.	0.00% 0/287 • Duration of treatment and follow up until death or 3 years post registration.
Gastrointestinal disorders Abdominal pain	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	1.0% 3/287 • Duration of treatment and follow up until death or 3 years post registration.
Gastrointestinal disorders Enterocolitis	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Gastrointestinal disorders Nausea	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.70% 2/287 • Duration of treatment and follow up until death or 3 years post registration.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.70% 2/287 • Duration of treatment and follow up until death or 3 years post registration.
General disorders Death NOS	1.5% 2/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
General disorders Disease progression	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.70% 2/287 • Duration of treatment and follow up until death or 3 years post registration.
Nervous system disorders Stroke	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Nervous system disorders Syncope	0.75% 1/134 • Duration of treatment and follow up until death or 3 years post registration.	0.00% 0/287 • Duration of treatment and follow up until death or 3 years post registration.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.75% 1/134 • Duration of treatment and follow up until death or 3 years post registration.	0.70% 2/287 • Duration of treatment and follow up until death or 3 years post registration.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders-Ot	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Surgical and medical procedures Surgical and medical procedures-Other	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Vascular disorders Hypotension	0.75% 1/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Vascular disorders Superior vena cava syndrome	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.35% 1/287 • Duration of treatment and follow up until death or 3 years post registration.
Vascular disorders Thromboembolic event	0.00% 0/134 • Duration of treatment and follow up until death or 3 years post registration.	0.70% 2/287 • Duration of treatment and follow up until death or 3 years post registration.