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

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Drug: Erlotinib; Drug: Docetaxel	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	25 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II Trial of Erlotinib in Combination With Docetaxel in Advanced Hepatocellular and Biliary Tract Carcinomas: Hoosier Oncology Group GI06-101
Study Start Date :	September 2007
Actual Primary Completion Date :	August 2010
Actual Study Completion Date :	August 2010

Arms and Interventions

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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

Outcome Measures

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Primary Outcome Measures :

1. 16 Weeks Progression-free Survival [ Time Frame: Start of treatment until disease progression per RECIST criteria up to 16 weeks ]
   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.

Secondary Outcome Measures :

1. Response Rate [ Time Frame: 18 months ]
   Determine the Response Rate Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)
2. Overall Survival [ Time Frame: 18 Months ]
   Determine Overall Survival

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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).

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Gabi Chiorean, MD

Sanofi

OSI Pharmaceuticals

Investigators

Study Chair:	Elena Gabriela Chiorean, M.D.	Hoosier Oncology Group, LLC

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Hoosier Oncology Group Home Page 

Publications of Results:

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.

Responsible Party:	Gabi Chiorean, MD, Principal Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:	NCT00532441 History of Changes
Other Study ID Numbers:	GI06-101
First Posted:	September 20, 2007
Results First Posted:	February 12, 2016
Last Update Posted:	February 12, 2016
Last Verified:	January 2016

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases	Liver Diseases; Docetaxel; Erlotinib Hydrochloride; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Protein Kinase Inhibitors; Enzyme Inhibitors