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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02392637
Recruitment Status : Active, not recruiting
First Posted : March 19, 2015
Last Update Posted : January 7, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE March 13, 2015
First Posted Date  ICMJE March 19, 2015
Last Update Posted Date January 7, 2020
Actual Study Start Date  ICMJE April 2, 2015
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 4, 2020)
Progression free survival (PFS) [ Time Frame: Up to 3 years ]
The Bayes factor single arm time-to-event model by Johnson & Cook will be used to monitor the PFS time.
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2015)
Progression-Free Survival (PFS) of Gemcitabine, Cisplatin, and Abraxane in Advanced Biliary Cancers [ Time Frame: 63 days ]
Response and progression evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1, 2009). The Bayes factor single arm time-to-event model by Johnson & Cook will be used to monitor the PFS time.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2020)
Incidence of adverse events [ Time Frame: Up to 35 days post-treatment ]
Toxicity will be monitored closely using the method of Thall et al.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2015)
Response Rate (RR) of Gemcitabine, Cisplatin, and Abraxane in Advanced Biliary Cancers [ Time Frame: 63 days ]
Response rate defined as partial response (PR), complete response (CR), and stable disease (SD). PR: At least a 30% decrease in sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. PR: At least a 30% decrease in sum of (LD) of target lesions taking as reference the baseline sum LD. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gemcitabine Hydrochloride, Cisplatin, and Nab-Paclitaxel in Treating Patients With Advanced or Metastatic Biliary Cancers
Official Title  ICMJE A Phase II Study of Gemcitabine, Cisplatin, and Abraxane in Advanced Biliary Cancers
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: Cisplatin
  • Drug: Gemcitabine Hydrochloride
  • Other: Laboratory Biomarker Analysis
  • Drug: Nab-paclitaxel
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 19, 2017)
62
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2015)
50
Estimated Study Completion Date  ICMJE April 30, 2020
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02392637
Other Study ID Numbers  ICMJE 2014-0524
NCI-2015-00578 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0524 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Milind Javle M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP