Erlotinib in Combination With Docetaxel in Advanced Hepatocellular and Biliary Tract Carcinomas

Phase II Trial of Erlotinib in Combination With Docetaxel in Advanced Hepatocellular and Biliary Tract Carcinomas: Hoosier Oncology Group GI06-101

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Erlotinib; Drug: Docetaxel

Detailed Description

Outline: This is a multi-center study.

Patients who meet eligibility criteria will receive treatment as follows until disease progression or excessive toxicities:

• Erlotinib 150 mg p.o. daily on days 2-7, 9-14, 16-28
• Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8, 15

Treatment cycle = 28 days

Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

Life expectancy: At least 12 weeks

Hematopoietic:

• Absolute neutrophil count (ANC) > 1000 mm3
• Platelet count > 75,000 mm3
• Hemoglobin > 8 g/dL

Hepatic:

• Bilirubin < 2.0 x upper limit of normal (ULN)
• Transaminases (AST, ALT) < 5.0 x ULN if alkaline phosphatase is < 2.5 x ULN, or alkaline phosphatase < 5 x ULN if transaminases are < 1.5 x ULN.
• If not on anticoagulation: PT < 4 seconds above ULN; INR < 1.5; PTT < 1.3 x ULN.
• If on therapeutic anticoagulation, patients may have an INR > 1.5 and PTT within therapeutic range; INR will be monitored weekly until stable.
• Serum Albumin > 3.0

Renal:

• Creatinine clearance of > 60 ml/ min (by Cockcroft-Gault)

Pulmonary:

• Not specified

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F. Graham Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Chicago, Illinois, United States, 60612
      • Rush-Presbyterian St. Luke's Medical Center
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • Cancer Care Center of Southern Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Oncology & Hematology, Inc
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • IN Onc/Hem Associates
    • Indianapolis, Indiana, United States, 46202
      • Quality Cancer Center (MCGOP)
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Siteman Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib and Docetaxel: Biliary; 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	Drug: Erlotinib; Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28; Drug: Docetaxel; Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15
Experimental: Erlotinib and Docetaxel: Hepatocellular; 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	Drug: Erlotinib; Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28; Drug: Docetaxel; Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
16 Weeks Progression-free Survival	To determine the rate of progression-free survival (PFS) at 16 weeks for the combination therapy of erlotinib and docetaxel for subjects in the Biliary stratum, per RECIST criteria. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions taking as reference the smallest sum recorded since the treatment started or the appearance of one or more new lesions.	Start of treatment until disease progression per RECIST criteria up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Determine the Response Rate Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)	18 months
Overall Survival	Determine Overall Survival	18 Months

Collaborators and Investigators

• Sponsor: Gabi Chiorean, MD
• Collaborators: Sanofi; OSI Pharmaceuticals
• Investigators: Study Chair: Elena Gabriela Chiorean, M.D., Hoosier Oncology Group, LLC

Publications and helpful links

General Publications

• Chiorean EG, Ramasubbaiah R, Yu M, Picus J, Bufill JA, Tong Y, Coleman N, Johnston EL, Currie C, Loehrer PJ. Phase II trial of erlotinib and docetaxel in advanced and refractory hepatocellular and biliary cancers: Hoosier Oncology Group GI06-101. Oncologist. 2012;17(1):13. doi: 10.1634/theoncologist.2011-0253. Epub 2011 Dec 30.

Helpful Links

• Hoosier Oncology Group Home Page

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: September 18, 2007
• First Submitted That Met QC Criteria: September 18, 2007
• First Posted (Estimate): September 20, 2007

Study Record Updates

• Last Update Posted (Estimate): February 12, 2016
• Last Update Submitted That Met QC Criteria: January 14, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protein Kinase Inhibitors; Docetaxel; Erlotinib Hydrochloride
• Other Study ID Numbers: GI06-101