Gemcitabine Hydrochloride, Cisplatin, and Nab-Paclitaxel in Treating Patients With Advanced or Metastatic Biliary Cancers

• ClinicalTrials.gov Identifier: NCT02392637
• Recruitment Status: Completed
• First Posted: March 19, 2015
• Results First Posted: February 2, 2022
• Last Update Posted: February 2, 2022
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Study Description

Brief Summary:

This phase II trial studies how well gemcitabine hydrochloride, cisplatin, and nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) work in treating patients with biliary cancers (which includes the gallbladder and bile ducts inside and outside the liver) that have spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as gemcitabine hydrochloride, cisplatin, and paclitaxel albumin-stabilized nanoparticle formulation, 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Condition or disease	Intervention/treatment	Phase
Stage III Intrahepatic Cholangiocarcinoma AJCC v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7; Stage IVB Gallbladder Cancer AJCC v7; Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7; Unresectable Extrahepatic Bile Duct Carcinoma; Unresectable Gallbladder Carcinoma	Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Nab-paclitaxel	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the progression-free survival (PFS) of gemcitabine hydrochloride (gemcitabine), cisplatin, and nab-paclitaxel in advanced, untreated biliary cancers (intrahepatic cholangiocarcinomas, extrahepatic cholangiocarcinomas, and gallbladder cancers).

SECONDARY OBJECTIVES:

I. Determine the response rate (RR) and disease control rate (partial response + complete response + stable disease) of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers.

II. Determine overall survival (OS) of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers.

III. Evaluate the toxicity of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers.

EXPLORATORY OBJECTIVES:

I. Correlate the carbohydrate antigen (CA) 19-9 response (defined as >50% decrease from baseline) with tumor response, PFS and OS.

II. Assess ribonucleotide reductase subunit MI (RRMI), excision repair cross-complementation group 1 (ERCC1) pre-treatment status and correlate with tumor response, PFS and OS on an exploratory basis.

III. Collect optional blood and tissue at the start of treatment and at progression to explore mechanisms of resistance.

OUTLINE:

Patients receive paclitaxel albumin-stabilized nanoparticle formulation 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.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Gemcitabine, Cisplatin, and Abraxane in Advanced Biliary Cancers
• Actual Study Start Date: April 2, 2015
• Actual Primary Completion Date: August 13, 2020
• Actual Study Completion Date: August 13, 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Treatment (nab-paclitaxel, cisplatin, gemcitabine); Patients receive paclitaxel albumin-stabilized nanoparticle formulation 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.

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; Other: Laboratory Biomarker Analysis; Correlative studies; 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

Outcome Measures

Primary Outcome Measures :

1. Median Progression Free Survival (PFS) [ Time Frame: up to 3 years ]
   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures :

1. Median Overall Survival (OS) [ Time Frame: up to 3 years ]
   The Kaplan-Meier method was used to estimate OS, with surviving patients censored at the time of surgery or at last known follow-up.
2. Number of Participants With Treatment Response Rate [ Time Frame: Up to 2 years ]
   Per Response Evaluation Criteria In Solid Tumors Criteria(RECIST v1.1.14) for target lesions and assessed by MRI: Complete Response (CR),Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient must have histologically or cytologically confirmed intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer or may undergo a repeat biopsy for histologic confirmation if pre-existing biopsy is not sufficient for diagnosis
• Metastatic or unresectable disease documented on diagnostic imaging studies
• May not have received prior chemotherapy; if patient has received prior adjuvant therapy, must be > 6 months from treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
• Platelets >= 100,000/ul
• Hemoglobin > 9.0 g/dL
• Total bilirubin =< 1.5 mg/dL (in patients with known Gilbert's syndrome direct bilirubin =< 1.5 x upper limit of normal [ULN] will be used as organ function criteria, instead of total bilirubin)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = < 5 x ULN
• Creatinine =< 1.5 gm/dL
• Negative serum or urine pregnancy test in women with childbearing potential (WOCBP) defined as not post-menopausal for 12 months or no previous surgical sterilization, within one week prior to initiation of treatment; WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy
• A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy; if the partner is pregnant or breastfeeding, the subject must use a condom
• Patients must sign an informed consent and authorization indicating that they are aware of the investigational nature of this study and the known risks involved

Exclusion Criteria:

• Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0; in CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)"
• Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infection
• Pregnancy (positive pregnancy test) or lactation
• Known central nervous system (CNS) disease, except for treated brain metastasis; treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period; anticonvulsants (stable dose) are allowed; treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic in Arizona

Scottsdale, Arizona, United States, 85259

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Texas

M D Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Milind Javle; M.D. Anderson Cancer Center

  Study Documents (Full-Text)

Documents provided by M.D. Anderson Cancer Center:

Study Protocol and Statistical Analysis Plan  [PDF] March 16, 2016

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, Raghav KPS, Iwasaki M, Masci P, Ramanathan RK, Ahn DH, Bekaii-Saab TS, Borad MJ. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):824-830. doi: 10.1001/jamaoncol.2019.0270.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02392637
• Other Study ID Numbers: 2014-0524; NCI-2015-00578 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2014-0524 ( Other Identifier: M D Anderson Cancer Center )
• First Posted: March 19, 2015
• Results First Posted: February 2, 2022
• Last Update Posted: February 2, 2022
• Last Verified: January 2022

• Studies a U.S. FDA-regulated Drug Product: Yes

Additional relevant MeSH terms:

Gallbladder Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma; Cholangiocarcinoma; Carcinoma, Ductal; Adenocarcinoma; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors