Phase II Trial of Nab-Paclitaxel and Gemcitabine for First-Line Treatment of Patients With Cholangiocarcinoma
Condition: Cholangiocarcinoma
MeSH terms: Cholangiocarcinoma
Intervention: Nab-Paclitaxel and Gemcitabine
Intervention description: Nab-Paclitaxel will be administered first, at a dose of 125 mg/m² IV over a period of 30 minutes; gemcitabine will be administered second, at a dose of 1000 mg/m² over a period of 30 minutes.
Intervention MeSH terms: Paclitaxel; Gemcitabine; Antimetabolites
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma; CCA; Bile Duct Cancer; Nab-Paclitaxel; Abraxane®; Gemcitabine; Gemzar®

Summary:

      Patients with advanced or metastatic cholangiocarcinoma (CCA) who are not eligible for
      curative surgery, transplantation, or ablative therapies will receive nab-paclitaxel and
      gemcitabine chemotherapy.

      The purpose of this study is to evaluate the effectiveness and safety of the combination of
      nab-paclitaxel and gemcitabine. The effectiveness will be determined by improvement in the
      length of time during and after treatment, that the CCA does not get worse.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have histologically-confirmed diagnosis of cholangiocarcinoma Stage II, III, or
             IV CCA (intra-hepatic, extra-hepatic and perihilar) that is not eligible for curative
             resection, transplantation, or ablative therapies. Tumors of mixed histology are not
             allowed.

          -  Must have radiographically measurable disease in at least one site not previously
             treated with radiation, chemoembolization, radioembolization, or other local ablative
             procedures; a new area of tumor progression within or adjacent to a previously-treated
             lesion, if clearly measurable by a Radiologist, is acceptable.

          -  May have received prior radiation, chemoembolization, radioembolization, or other
             local ablative therapies, or hepatic resection if completed ≥ 4 weeks prior to
             registration AND if patient has recovered to ≤ grade 1 toxicity. NOTE: Measurable
             disease (as required above) must still be present.

          -  May have received prior radiation for bone or brain metastases if patient is now
             asymptomatic and has completed all radiation and steroid therapy (if applicable) ≥ 2
             weeks prior to registration.

          -  Age ≥ 18 years.

          -  Child-Pugh score of A or B with ≤ 7 points.

          -  Eastern Cooperative Oncology Group performance status of 0-1.

          -  Willing to provide archived tissue, if available, from a previous diagnostic biopsy.

          -  Must be able to tolerate CT and/or MRI with contrast.

          -  Adequate organ function obtained ≤ 2 weeks prior to registration:

               -  Absolute Neutrophil Count ≥ 1500/mm³

               -  Hemoglobin ˃9.0 g/dL

               -  Platelets ˃100,000/mm³

               -  Serum Creatinine ≤ 1.5x Upper Limit Normal (ULN)

               -  Creatinine Clearance ≥ 50 mL/min

               -  Albumin ≥ 2.8 g/dL

               -  Total Bilirubin ≤ 1.5 mg/dL or ≤ 1.5x ULN

               -  Aspartate Aminotransaminase (AST)/Alanine Aminotransaminase (ALT) ≤ 2.5x ULN (≤
                  5x ULN in patients with liver metastases)

               -  International Normalized Ratio (INR) <1.5x the ULN [INR ≥ 1.5 is allowed if
                  anticoagulation is used.]

          -  Women must not be pregnant or breastfeeding since nab-paclitaxel and/or gemcitabine
             may harm the fetus or child.

          -  Must not have received prior systemic cytotoxic chemotherapy or targeted therapy for
             this cancer.

          -  Must not be receiving treatment with other investigational agents.

          -  Must not have a pre-existing >grade 2 peripheral neuropathy.

          -  Must not be receiving immunosuppressive medications, including systemic
             corticosteroids, aside from the following exceptions: used for adrenal replacement,
             appetite stimulation, therapy for asthma, bronchitis exacerbation (≤ 2 weeks),
             anti-emesis, or pre-medication for procedures (i.e. CT scan).

          -  No known Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV)
             seropositivity.

          -  Must not have undergone liver transplantation.

          -  Must not have serious non-healing wound, ulcer, bone fracture, or abscess.

          -  Must not have undergone a major surgical procedure <4 weeks prior to registration.

          -  Must not have possible histories of pneumonitis or pneumonitis risk factors.

          -  Must not have an active second malignancy other than non-melanoma skin cancer or
             cervical carcinoma in situ.

          -  Must have no ongoing or active, uncontrolled infections.

          -  Must have no evidence of significant, uncontrolled concomitant diseases including, but
             not limited to: symptomatic congestive heart failure, unstable angina pectoris,
             uncontrolled cardiac arrhythmia, myocardial infarction within preceding 12 months,
             uncontrolled peripheral vascular disease, cerebrovascular accident within preceding 12
             months, pulmonary disease impairing functional status or requiring oxygen, connective
             tissue disease including lupus.

          -  Must not have any history of allergic reaction(s) attributed to compounds of similar
             composition to nab-paclitaxel or gemcitabine.