A Single-Arm Feasibility Study of Gemcitabine, Cisplatin, and Nab-Paclitaxel as Neoadjuvant Therapy for Resectable Oncologically High-Risk Intrahepatic Cholangiocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Cisplatin
- Conditions
- Resectable Cholangiocarcinoma
- Sponsor
- Emory University
- Enrollment
- 30
- Locations
- 7
- Primary Endpoint
- Number of Participants Who Completed All Preoperative and Operative Therapy
- Status
- Completed
- Last Updated
- 8 months ago
Overview
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.
Investigators
Shishir Kumar Maithel
Principal Investigator
Emory University
Eligibility 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: (must meet at least one of the criteria below)
- •T-stage ≥ Ib (Ib-IV)
- •Solitary lesion \> 5 cm
- •Multifocal tumors or satellite lesions present confined to the same lobe of the liver as the dominant lesion but still technically resectable
- •Presence of major vascular invasion but still technically resectable
- •Suspicious or involved regional lymph nodes (N1)
- •No distant extrahepatic disease (M0)
- •Able to give informed consent.
- •Able to adhere to study visit schedule and other protocol requirements.
Exclusion Criteria
- •Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.
- •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.
Arms & Interventions
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.
Intervention: Cisplatin
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.
Intervention: Gemcitabine
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.
Intervention: Nab-paclitaxel
Outcomes
Primary Outcomes
Number of Participants Who Completed All Preoperative and Operative Therapy
Time Frame: Up to 12 weeks after study start
Completion of all therapy rate will be recorded.
Number of Participants With 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 Outcomes
- 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(Up to 12 weeks after study start)
- Recurrence-free Survival (RFS)(From the date of surgery up to 3 years)
- Number of Participants With Overall Survival(From date of neoadjuvant treatment start up to 3 years)