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Gemcitabine, Cisplatin, and Nab-Paclitaxel Before Surgery in Patients With High-Risk Liver Bile Duct Cancer

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ClinicalTrials.gov Identifier: NCT03579771
Recruitment Status : Recruiting
First Posted : July 9, 2018
Last Update Posted : March 8, 2019
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
Shishir Kumar Maithel, Emory University

Tracking Information
First Submitted Date  ICMJE June 26, 2018
First Posted Date  ICMJE July 9, 2018
Last Update Posted Date March 8, 2019
Actual Study Start Date  ICMJE September 26, 2018
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
  • Completion of all preoperative and operative therapy [ Time Frame: Up to 12 weeks after study start ]
    Completion of all therapy rate will be recorded.
  • Incidence of adverse events [ Time Frame: Up to 3 years after study start ]
    Will be monitored using method of Thall, Simon and Estey, and will be tabulated by the maximum reported Common Terminology Criteria for Adverse Events (CTCAE) grade.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03579771 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
  • Radiological response rate defined as the percentage of patients who will have complete response (CR), partial response (PR) or stable disease (SD) after the neoadjuvant therapy [ Time Frame: Up to 12 weeks after study start ]
    Will be evaluated according to Response Evaluation Criteria in Solid Tumor (RECIST).
  • Recurrence-free survival (RFS) [ Time Frame: From the date of surgery up to 3 years ]
    RFS is defined as the time between the date of surgery and the date of disease recurrence or death, whichever occurred first. If a patient did not have an event (i.e. disease recurrence or death) by the time of final analysis, patient will be censored at the last disease evaluation time.
  • Overall survival (OS) [ Time Frame: From date of neoadjuvant treatment start up to 3 years ]
    OS is defined as the time from date of neoadjuvant treatment start to the date of death from any cause or to the date of last follow-up if patients are alive. If a patient is alive by the time of final analysis, the patient will be censored at the last follow-up date.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gemcitabine, Cisplatin, and Nab-Paclitaxel Before Surgery in Patients With High-Risk Liver Bile Duct Cancer
Official Title  ICMJE A Single-Arm Feasibility Study of Gemcitabine, Cisplatin, and Nab-Paclitaxel as Neoadjuvant Therapy for Resectable Oncologically High-Risk Intrahepatic Cholangiocarcinoma
Brief Summary This phase II trial studies how well gemcitabine, cisplatin, and nab-paclitaxel work before surgery in treating participants with high-risk bile duct cancer in the liver (intrahepatic cholangiocarcinoma). Drugs used in chemotherapy, such as nab-paclitaxel, cisplatin, and gemcitabine, 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 combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed Description

PRIMARY OBJECTIVE:

To assess the feasibility of therapeutic approach that includes neoadjuvant chemotherapy including gemcitabine hydrochloride (gemcitabine), cisplatin, and nab-paclitaxel for high-risk but technically resectable intrahepatic cholangiocarcinoma and is completed with surgical resection.

SECONDARY OBJECTIVES:

I. To assess the radiological response rate to neoadjuvant systemic chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST).

II. To determine the R0 resection rate.

III. To determine patient recurrence-free survival (RFS).

IV. To identify patient overall survival (OS) rate.

OUTLINE:

Participants receive nab-paclitaxel intravenously (IV) over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.

After completion of study treatment, participants are followed up every 4 months for 3 years.

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
  • Resectable Cholangiocarcinoma
  • Stage IB Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage II Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage III Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8
  • Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8
Intervention  ICMJE
  • Drug: Cisplatin
    Given IV
    Other Names:
    • CDDP
    • Cis-diamminedichloridoplatinum
    • Cismaplat
    • Cisplatinum
    • Neoplatin
    • Platamin
    • Platinol
  • Drug: Gemcitabine
    Given IV
    Other Names:
    • dFdCyd
    • Difluorodeoxycytidine hydrochloride
    • Gemcitabine hydrochloride
    • Gemzar
  • Drug: Nab-paclitaxel
    Given IV
    Other Names:
    • ABI-007
    • Abraxane
    • Nanoparticle albumin-bound paclitaxel
Study Arms  ICMJE Experimental: Gemcitabine, cisplatin, nab-paclitaxel
Participants receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Participants with stable disease (SD), partial response (PR), or complete response (CR) then undergo standard of care hepatectomy with portal lymphadenectomy.
Interventions:
  • Drug: Cisplatin
  • Drug: Gemcitabine
  • Drug: Nab-paclitaxel
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 26, 2018)
34
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2024
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of intrahepatic cholangiocarcinoma.
  • High-quality cross-sectional imaging by computerized tomography (CT) or magnetic resonant imaging (MRI) performed within 6 weeks prior to enrollment and showed a resectable, but high-risk, intrahepatic cholangiocarcinoma (IHCCA) confined to the liver, bile duct, and/or regional lymph nodes. Tumors will be considered high-risk if the high-quality, contrast-enhanced CT and/or MRI +/- positron emission tomography (PET) scan showed:

    1. T-stage ≥ Ib (Ib-IV)
    2. Solitary lesion > 5 cm
    3. Multifocal tumors or satellite lesions present confined to the same lobe of the liver as the dominant lesion but still technically resectable
    4. Presence of major vascular invasion but still technically resectable
    5. Suspicious or involved regional lymph nodes (N1)
    6. No distant extrahepatic disease (M0)
  • Able to give informed consent.
  • Able to adhere to study visit schedule and other protocol requirements.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Absolute neutrophil count (ANC) ≥ 1,500 cells/μL
  • Platelet count ≥ 100,000 cells/μL
  • Hemoglobin ≥ 9 g/dL
  • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Albumin ≥ 3 g/dL
  • Creatinine ≤ 1.5 x ULN
  • Non-pregnant and non-lactating.
  • Women of child-bearing potential (defined as a sexually mature woman who [1] has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption for 28 days prior to starting gemcitabine/cisplatin/nab-paclitaxel (including dose interruptions) until treatment with gemcitabine/cisplatin/nab-paclitaxel is complete.
  • Male subjects must practice true abstinence or agree to use a condom during sexual contact with a female of childbearing potential or a pregnant female while on treatment (including during dose interruptions) with gemcitabine/cisplatin/nab-paclitaxel and for 6 months following gemcitabine/cisplatin/nab-paclitaxel discontinuation, even if he has undergone a successful vasectomy.

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, symptomatic congestive heart failure, uncontrolled diabetes, serious active, uncontrolled infection after inadequate biliary drainage if tumor obstructing bile duct, or psychiatric illness/social situations.
  • 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 (MRI or 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.
  • Previous (within the past 5 years) or concurrent presence of other cancer, except non-melanoma skin cancer and in situ carcinomas.
  • History of allergy or hypersensitivity to any of the study drugs.
  • Current abuse of alcohol or illicit drugs.
  • Inability or unwillingness to sign the informed consent form.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shishir Maithel, MD 404-712-3308 smaithe@emory.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03579771
Other Study ID Numbers  ICMJE IRB00104175
NCI-2018-00998 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EU4339-18 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shishir Kumar Maithel, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE Celgene
Investigators  ICMJE
Principal Investigator: Shishir Maithel, MD Emory University
PRS Account Emory University
Verification Date March 2019

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