Clinical trial NCT03579771: Gemcitabine, Cisplatin, and Nab-Paclitaxel Before Surgery in Patients With High-Risk Liver Bile Duct Cancer
Official title: A Single-Arm Feasibility Study of Gemcitabine, Cisplatin, and Nab-Paclitaxel as Neoadjuvant Therapy for Resectable Oncologically High-Risk Intrahepatic Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Celgene
name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2018-07-09
Enrollment: 31
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

  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)
* 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.

Primary outcomes:
measure: Completion of all preoperative and operative therapy
timeFrame: Up to 12 weeks after study start
measure: Incidence of adverse events
timeFrame: Up to 3 years after study start
Secondary outcomes:
measure: 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
timeFrame: Up to 12 weeks after study start
measure: Recurrence-free survival (RFS)
timeFrame: From the date of surgery up to 3 years
measure: Overall survival (OS)
timeFrame: From date of neoadjuvant treatment start up to 3 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
Study officials:
affiliation: Emory University
name: Shishir Maithel, MD
role: PRINCIPAL_INVESTIGATOR
References: