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

- 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) 5.0. 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