Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers
Condition: Hepatocellular Carcinoma; Cholangiocellular Carcinoma; Cholangiocarcinoma of the Extrahepatic Bile Duct; Bile Duct Cancer; Periampullary Adenocarcinoma; Gallbladder Cancer; Extrahepatic Bile Duct Cancer
MeSH terms: Carcinoma; Adenocarcinoma; Carcinoma, Hepatocellular; Cholangiocarcinoma; Gallbladder Neoplasms; Bile Duct Neoplasms
Intervention: Cisplatin; Erlotinib; Gemcitabine
Intervention description: Cisplatin is administered intravenously at 40 mg/m2 on day 1 and day 15, every 28 days. Cisplatin is administered following Gemcitabine. Cisplatin administration should occur with hydration with normal saline at 250 mL/ hour for at least 4 hours before and during Cisplatin administration. Additionally, Cisplatin administration should be preceded by osmotic diuresis with Mannitol 25%, 12.5 grams.; 100 mg orally daily. For grade 3 or 4 skin rash, erlotinib should be held until resolution of the rash to no more than grade 1 before resumption of erlotinib.; Gemcitabine is administered intravenously at 1000 mg/m2 on day 1 and 15, every 28 days. The clinical formulation is supplied in a sterile form for intravenous use only. Vials of gemcitabine contain either 200 mg or 1 g of gemcitabine hydrochloride (HCl )(expressed as free base) formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophilized powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.
Intervention MeSH terms: Gemcitabine; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Liver; Gallbladder; Bile duct; Gemzar; Eloxatin; Tarceva; erlotinib; Gem-ox

Summary:

      This is a single arm phase II trial of Gemcitabine and Oxaliplatin (Gem-Ox) with Erlotinib
      (Tarceva) for the treatment of hepatocellular carcinoma (HCC) and biliary tree cancer (BTC)
      patients with platelet counts 100,000/µL. The purpose of this study is to determine the tumor
      control rate following treatment with GEM-OX combined with Tarceva in patients with HCC.
      Tumor control rate is defined as the percentage of patients achieving a complete response,
      partial response, or stable disease at 24 weeks following treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed hepatocellular carcinoma (HCC) or biliary
             tree cancer (BTC:: intra- and extra-hepatic cholanciocarcinoma, bile duct cancer,
             adenocarcinoma of the Ampulla of Vater and/or gallbladder carcinoma).

          -  Patients must have measurable disease according to Response Evaluation Criteria in
             Solid Tumors (RECIST).

          -  Age 18 years or older.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2

          -  Adequate bone marrow as evidenced by:

               -  Absolute neutrophil count (ANC) > 1,500/L.

               -  Platelet count > 100,000/L.

               -  Absence of a regular red blood cell transfusion requirement.

          -  Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL.

          -  Adequate hepatic function as evidenced by:

               -  Serum total bilirubin 1.5x Upper Limit of Normal (ULN).

               -  Alkaline phosphatase < 3x ULN for the reference lab (< 5x ULN for patients with
                  known hepatic metastases).

               -  Serum glutamic-oxaloacetic transaminase (SGOT)/ serum glutamic-pyruvic
                  transaminase (SGPT) < 3x ULN for the reference lab (< 5x ULN for patients with
                  known hepatic metastases).

          -  Patients must have a life expectancy of 12 weeks.

          -  Patients must be recovered from both acute and late effects of any prior surgery,
             radiotherapy or other antineoplastic therapy.

          -  Patients of childbearing potential agree to use an effective form of contraception
             during the study and for 90 days following the last dose of study medication (an
             effective form of contraception is an oral contraceptive or a double barrier method).

        Exclusion Criteria:

        A patient may not be enrolled in the trial if any of the following criteria are met:

          -  Patients with an active infection or with a fever > 38.50 degrees Celcius within 3
             days of the first scheduled day of protocol treatment.

          -  Patients with active central nervous system (CNS) metastases. Patients with stable CNS
             disease, who have undergone radiotherapy at least 4 weeks prior to the planned first
             protocol treatment and who have been on a stable dose of corticosteroids for 3 weeks
             are eligible for the trial.

          -  History of prior malignancy within the past 5 years except for curatively treated
             basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized
             prostate cancer with a current prostate serum antigen (PSA) of < 1.0 mg/dL on 2
             successive evaluations at least 3 months apart, with the most recent evaluation within
             4 weeks of entry.

          -  Patients with prior treatment or known hypersensitivity to any of the components of
             oxaliplatin or gemcitabine.

          -  Patients who have received chemotherapy within 30 days of the first scheduled day of
             protocol treatment.

          -  Patients who received radiotherapy to more than 25% of their bone marrow; or patients
             who received any radiotherapy within 4 weeks of entry.

          -  Patients who are receiving concurrent investigational therapy or who have received
             investigational therapy within 30 days of the first scheduled day of protocol
             treatment (investigational therapy is defined as treatment for which there is
             currently no regulatory authority approved indication).

          -  Peripheral neuropathy Grade 2.

          -  Patients who are pregnant or lactating.

          -  Patients with a life expectancy of less than 12 weeks.

          -  Any other medical condition, including mental illness or substance abuse, deemed by
             the Investigator, likely to interfere with a patient's ability to sign informed
             consent, cooperate and participate in the study, or interfere with the interpretation
             of the results.

          -  Patients with any of the following laboratory parameters:

               -  Abnormal hematological values with ANC < 1500/mm3, thrombocytopenia < 99,000.

               -  Impaired renal function with a serum creatinine > 1.5x ULN.

               -  Serum bilirubin > 1.5xULN.

               -  Albumin < 2.5 mg/dl.

          -  Unwillingness to participate or inability to comply with the protocol for the duration
             of the study.

          -  History of allogeneic transplant.

          -  Known human immunodeficiency virus (HIV).

          -  Clinically significant heart disease defined as New York Heart Association (NYHA)
             class 3 or 4 heart disease.

          -  Known or existing uncontrolled coagulopathy.

          -  Patients with severe medical problems such as uncontrolled diabetes or chronically
             debilitating diseases that the investigator feels might compromise the study
             participant.