A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers
Overview
- Phase
- Phase 3
- Intervention
- Cisplatin
- Conditions
- Stage III Distal Bile Duct Cancer AJCC v8
- Sponsor
- SWOG Cancer Research Network
- Enrollment
- 452
- Locations
- 1303
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief Summary
This phase III trial studies how well gemcitabine hydrochloride and cisplatin given with or without nab-paclitaxel work in treating patients with newly diagnosed biliary tract cancers that have spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride, cisplatin, and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not known if giving gemcitabine hydrochloride and cisplatin with or without nab-paclitaxel may work better at treating biliary tract cancers.
Detailed Description
PRIMARY OBJECTIVES: I. To compare overall survival (OS) in patients with untreated, advanced biliary cancers treated with gemcitabine hydrochloride (gemcitabine) and cisplatin (GC) versus those treated with gemcitabine, cisplatin, and nab-Paclitaxel (GCN). SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS) in patients treated with GC versus GCN. II. To compare overall response rate (ORR), complete and partial, confirmed and unconfirmed, in the subset of patients with measurable disease treated with GC versus GCN. III. To compare disease control rate (confirmed and unconfirmed; complete response + partial response + stable disease) (DCR) in patients treated with GC versus GCN. IV. To evaluate the frequency and severity of toxicity associated with GC and GCN in the patient population. V. To explore the correlation between change in cancer antigen 19-9 (CA19-9) levels from baseline to post-treatment (after 3 cycles) and overall response rate, in each treatment arm separately and in the total cohort. ADDITIONAL OBJECTIVES: I. To bank tissue and blood for future translational medicine studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive nab-paclitaxel intravenously (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. ARM II: 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. After completion of study treatment, patients are followed up every 6 months for 2 years and then at the end of year 3.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer
- •NOTE: Pathology report must be uploaded in Rave. Histology report must be consistent with an adenocarcinoma with pancreaticobiliary primary assuming there are no pancreatic lesions and other primaries are ruled out per local standard
- •Patients must have documented metastatic or locally advanced unresectable disease on computed tomography (CT) or magnetic resonance (MR) imaging CT scans or MRIs used to assess measurable disease. Must have been completed within 28 days prior to registration. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form
- •Patient must not have a current diagnosis of ampullary cancer
- •Patients must not have received prior systemic therapy for the current metastatic or locally advanced biliary cancer
- •Patient must not have received adjuvant therapy within 6 months prior to registration
- •Patients must have a complete medical history and physical exam within 28 days prior to registration
- •Patients must have a Zubrod performance status of 0 or 1
- •Patients must not have a history of peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 5.
- •In CTCAE version 5.0 grade 2 sensory neuropathy is defined as ?moderate symptoms; limiting instrumental activities of daily living (ADLs)?
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (nab-paclitaxel, cisplatin, gemcitabine hydrochloride)
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.
Intervention: Cisplatin
Arm I (nab-paclitaxel, cisplatin, gemcitabine hydrochloride)
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.
Intervention: Gemcitabine Hydrochloride
Arm I (nab-paclitaxel, cisplatin, gemcitabine hydrochloride)
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.
Intervention: Nab-paclitaxel
Arm II (cisplatin, gemcitabine hydrochloride)
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.
Intervention: Cisplatin
Arm II (cisplatin, gemcitabine hydrochloride)
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.
Intervention: Gemcitabine Hydrochloride
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to 3 years
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.
Secondary Outcomes
- Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs.(Duration of treatment and follow-up until death or 3 years post registration.)
- Progression-free Survival (PFS)(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)
- Overall Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria(Up to 3 years)
- Disease Control Rate as Measured by RECIST 1.1 Criteria(Up to 3 years)
- Changes in Carbohydrate Antigen 19-9 (CA 19-9) Levels(Baseline up to course 3)