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

• ClinicalTrials.gov Identifier: NCT03768414
• Recruitment Status: Recruiting
• First Posted: December 7, 2018
• Last Update Posted: November 7, 2019
• Sponsor: Southwest Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Southwest Oncology Group

Tracking Information

• First Submitted Date: December 6, 2018
• First Posted Date: December 7, 2018
• Last Update Posted Date: November 7, 2019
• Actual Study Start Date: December 3, 2018
• Estimated Primary Completion Date: January 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 6, 2018)

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.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03768414 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 6, 2018)

• Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 3 years ]
  Rates of serious toxicities will be compared between arms.
• Progression-free survival (PFS) [ Time Frame: 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 ]
  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.
• Overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria [ Time Frame: 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.
• Disease control rate as measured by RECIST 1.1 criteria [ Time Frame: 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.
• Changes in carbohydrate antigen 19-9 (CA 19-9) levels [ Time Frame: Baseline up to course 3 ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gemcitabine Hydrochloride and Cisplatin With or Without Nab-Paclitaxel in Treating Patients With Newly Diagnosed Advanced Biliary Tract Cancers
• Official Title: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Stage III Distal Bile Duct Cancer AJCC v8
• Stage III Gallbladder Cancer AJCC v8
• Stage III Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IIIA Distal Bile Duct Cancer AJCC v8
• Stage IIIA Gallbladder Cancer AJCC v8
• Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IIIB Distal Bile Duct Cancer AJCC v8
• Stage IIIB Gallbladder Cancer AJCC v8
• Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IV Distal Bile Duct Cancer AJCC v8
• Stage IV Gallbladder Cancer AJCC v8
• Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IVA Gallbladder Cancer AJCC v8
• Stage IVB Gallbladder Cancer AJCC v8
• Unresectable Extrahepatic Bile Duct Carcinoma
• Unresectable Gallbladder Carcinoma
• Unresectable Intrahepatic Cholangiocarcinoma

Intervention

• Drug: Cisplatin
  Given IV
  Other Names:

  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
• Drug: Gemcitabine Hydrochloride
  Given IV
  Other Names:

  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
• Drug: Nab-paclitaxel
  Given IV
  Other Names:

  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • paclitaxel albumin-stabilized nanoparticle formulation
  • Protein-bound Paclitaxel

Study Arms

• Experimental: 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.
  Interventions:

  • Drug: Cisplatin
  • Drug: Gemcitabine Hydrochloride
  • Drug: Nab-paclitaxel
• Experimental: 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.
  Interventions:

  • Drug: Cisplatin
  • Drug: Gemcitabine Hydrochloride

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 6, 2018): 268
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2024
• Estimated Primary Completion Date: January 1, 2024 (Final data collection date for primary outcome measure)

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) 5.0. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Danae Campos; 210-614-8808 ext 1022; dcampos@swog.org

Contact: Dana Sparks; 210-614-8808 ext 1004; dsparks@swog.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03768414
• Other Study ID Numbers: S1815; NCI-2018-01920 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); S1815 ( Other Identifier: SWOG ); S1815 ( Other Identifier: CTEP ); U10CA180888 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Southwest Oncology Group
• Study Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Rachna Shroff; Southwest Oncology Group

• PRS Account: Southwest Oncology Group
• Verification Date: November 2019