A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers
A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers
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.
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.
Inclusion Criteria:
Patients must have histologically or cytologically confirmed intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer
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) 5.0. In CTCAE version 5.0 grade 2 sensory neuropathy is defined as ?moderate symptoms; limiting instrumental activities of daily living (ADLs)?
Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 28 days prior to registration)
Platelets >= 100,000/mcL (obtained within 28 days prior to registration)
Hemoglobin >= 8 g/dL (obtained within 28 days prior to registration)
Serum albumin >= 2.8 g/dL (obtained within 28 days prior to registration)
Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except patients with Gilbert?s syndrome, who must have a direct bilirubin < 1.5 mg/dL) (obtained within 28 days prior to registration)
Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 8 x IULN (obtained within 28 days prior to registration)
Serum creatinine =< IULN OR calculated creatinine clearance >= 60 mL/min (obtained within 28 days prior to registration)
Patients must have CA19-9 obtained within 42 days prior to registration
Patients must have sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), calcium, total protein, magnesium, and alkaline phosphatase obtained within 28 days prior to registration
Patients must not have an active infection requiring systemic therapy
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for two years
Patients must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Sites must seek additional patient consent for the future use of specimens
Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Jonesboro, Arkansas 72401, United States
Burbank, California 91505, United States
Sacramento, California 95817, United States
Pekin, Illinois 61554, United States
Louisville, Kentucky 40202, United States
Brownstown, Michigan 48183, United States
Norton Shores, Michigan 49444, United States
Columbus, Mississippi 39705, United States
New Albany, Mississippi 38652, United States
Las Vegas, Nevada 89109, United States
Las Vegas, Nevada 89113, United States
Las Vegas, Nevada 89149, United States
Collierville, Tennessee 38017, United States
Houston, Texas 77030, United States
Berlin Corners, Vermont 05602, United States
Vancouver, Washington 98684, United States
Sturgeon Bay, Wisconsin 54235-1495, United States
Summit, Wisconsin 53066, United States