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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 : May 20, 2019
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
Shishir Kumar Maithel, Emory University

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.

Condition or disease Intervention/treatment Phase
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 Drug: Cisplatin Drug: Gemcitabine Drug: Nab-paclitaxel Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm Feasibility Study of Gemcitabine, Cisplatin, and Nab-Paclitaxel as Neoadjuvant Therapy for Resectable Oncologically High-Risk Intrahepatic Cholangiocarcinoma
Actual Study Start Date : September 26, 2018
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : September 30, 2024


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. Completion of all preoperative and operative therapy [ Time Frame: Up to 12 weeks after study start ]
    Completion of all therapy rate will be recorded.

  2. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03579771


Contacts
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Contact: Shishir Maithel, MD 404-778-5777 smaithe@emory.edu

Locations
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United States, Arizona
Mayo Clinic in Arizona Not yet recruiting
Scottsdale, Arizona, United States, 85259
Contact: Shishir Maithel, MD       smaithe@emory.edu   
Principal Investigator: Mitesh Borad, MD         
United States, Florida
Mayo Clinic in Florida Not yet recruiting
Jacksonville, Florida, United States, 32224
Contact: Shishir Maithel       smaithe@emory.edu   
Principal Investigator: Kabir Mody, MD         
Principal Investigator: Kristopher Croome, MD         
United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Swathi Chinaranagari    404-686-0239    swathi.chinaranagari@emory.edu   
Contact: Shabnam Montazeri    404-686-0242    shabnam.montazeri@emory.edu   
Principal Investigator: Shishir Maithel, MD         
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Tyra Gaines    404-712-3308    tgaine3@emory.edu   
Contact: Sheena Abraham    404-778-2670    sheena.abraham@emory.edu   
Principal Investigator: Shishir Maithel, MD         
Emory Saint Joseph's Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Alicia Escobar    678-843-7029    alicia.m.escobar@emory.edu   
Contact: Krystal Reese    678-843-5911    krystal.reese@emory.edu   
Principal Investigator: Shishir Maithel, MD         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Shishir Maithel, MD       smaithe@emory.edu   
Principal Investigator: Amit Mahipal, MD         
Principal Investigator: Rory Smoot, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jean Vauthey, MD    713-792-2022    jvauthey@mdanderson.org   
Contact: Kandice Rachal    713-745-8434    krrachal@mdanderson.org   
Principal Investigator: Jean-Nicolas Vauthey, MD         
Principal Investigator: Milind Javle, MD         
United States, Washington
Benaroya Research Institute at Virginia Mason Recruiting
Seattle, Washington, United States, 98101
Contact: Anas Najjar, MS    206-287-6271    anas.najjar@virginiamason.org   
Contact: Shishir Maithel, MD       smaithe@emory.edu   
Principal Investigator: Flavio G. Rocha, MD         
Principal Investigator: Bruce Lim, MD         
Sponsors and Collaborators
Emory University
Celgene
Investigators
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Principal Investigator: Shishir Maithel, MD Emory University

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Responsible Party: Shishir Kumar Maithel, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03579771     History of Changes
Other Study ID Numbers: IRB00104175
NCI-2018-00998 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EU4339-18 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
First Posted: July 9, 2018    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
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
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs