Erlotinib in Combination With Docetaxel in Advanced Hepatocellular and Biliary Tract Carcinomas
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma
Intervention: Erlotinib; Docetaxel
Intervention description: Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28; Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15
Intervention MeSH terms: Docetaxel; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      An unmet medical need exists for the successful therapy of patients with advanced
      hepatocellular and biliary tract malignances, with few and short lived disease responses to
      chemotherapy for both advanced stage hepatic and biliary carcinomas. Pre-clinical data shows
      cooperative antitumor activity between an epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor and taxanes. The efficacy of erlotinib in combination with docetaxel will be
      assessed in this trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological proof of hepatocellular or biliary tract carcinomas, not
             amenable to curative resection or transplantation.

          -  Prior cancer treatment completed at least 30 days prior to being registered for
             protocol therapy and recovered from the acute toxicity effects of the regimen.

          -  Patients may have had radiofrequency ablation, cryosurgery or embolization, but must
             have documented progressive disease with the involved lesion, or at least one
             previously untreated lesion.

          -  Patients may have had ≤ 2 prior chemotherapy regimens.

          -  Prior radiation therapy allowed to < 25% of the bone marrow at least 30 days prior to
             being registered for protocol therapy.

          -  Patients with biliary obstruction must have percutaneous transhepatic drainage or
             endoscopic stent placement prior to starting study treatment.

          -  Patients with a history of malignancy are eligible provided they have been curatively
             treated and demonstrate no evidence for recurrence of that cancer.

          -  Peripheral neuropathy ≤ grade 1.

          -  Patients must agree to abstain from frozen or fresh grapefruit or grapefruit juice for
             5 days prior to, and during treatment.

          -  Patients must be willing to use an effective method of contraception (hormonal or
             barrier method of birth control; abstinence) while on treatment and for a 12 week
             period thereafter.

          -  Females of childbearing potential must have a negative pregnancy test within 7 days
             prior to being registered for protocol therapy.

          -  Written informed consent and HIPAA authorization for release of personal health
             information.

          -  Age ≥ 18 years at time of consent.

        Exclusion Criteria:

          -  No previous treatment with EGFR inhibitors.

          -  No treatment with any investigational agent within 30 days prior to being registered
             for protocol therapy.

          -  No symptomatic brain metastasis. A subject with prior brain metastasis may be
             considered if they have completed their treatment for brain metastasis, no longer
             require corticosteroids, and are asymptomatic.

          -  No Child-Pugh B or C liver cirrhosis.

          -  No active corneal erosions or history of abnormal corneal sensitivity test.

          -  No history of aneurysm or arteriovenous malformation.

          -  No hemorrhage/bleeding event > CTCAE Grade 3 within 30 days prior to begin registered
             for protocol therapy.

          -  No clinically significant infections as judged by the treating investigator.

          -  No condition that impairs patient's ability to swallow whole pills.

          -  No history of hypersensitivity to docetaxel or other drugs formulated with polysorbate
             80.

          -  Females must not be breastfeeding.

          -  Patients who cannot avoid the following medications will be ineligible for the trial:
             midazolam, anti-mycotic agents (ketoconazole and related compounds), macrolide
             antibiotics (erythromycin and related compounds), nifedipine, phenobarbital,
             phenytoin, carbamazepine, and rifampin (induction) and anti-retrovirals (including
             ritonavir, saquinavir).