Hepatocellular Carcinoma
Conditions
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.
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
Interventions
DRUGErlotinib
Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28
DRUGDocetaxel
Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15
Sponsors
Sanofi
OSI Pharmaceuticals
Gabi Chiorean, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 16 Weeks Progression-free Survival | 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
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 18 months | Determine the Response Rate Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) |
| Overall Survival | 18 Months | Determine Overall Survival |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib and Docetaxel 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
Erlotinib: Erlotinib 150 mg p.o. daily, days 2-7, 9-14, 16-28
Docetaxel: Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8 and 15 | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Erlotinib and Docetaxel |
|---|---|
| Age, Customized Age | 63.5 years |
| Biliary Cancer Site Cholangiocarcoma | 6 participants |
| Biliary Cancer Site Gallbladder | 5 participants |
| Biliary Cancer Site N/A | 14 participants |
| Cancer Type or Histologic Subtype Biliary | 11 participants |
| Cancer Type or Histologic Subtype Hepatocellular | 14 participants |
| Disease Status Locally Advanced: Biliary | 0 participants |
| Disease Status Locally Advanced: Hepatocellular | 4 participants |
| Disease Status Metastatic: Biliary | 11 participants |
| Disease Status Metastatic: Hepatocellular | 10 participants |
| ECOG Performance Status ECOG 0 | 11 participants |
| ECOG Performance Status ECOG 1 | 12 participants |
| ECOG Performance Status ECOG 2 | 2 participants |
| Number of Prior Systemic Therapies Biliary: 1 Prior therapy | 6 participants |
| Number of Prior Systemic Therapies Biliary: >1 Prior Therapy | 1 participants |
| Number of Prior Systemic Therapies Hepatocellular: >1 Prior Therapy | 2 participants |
| Number of Prior Systemic Therapies Hepatocellular: 1 Prior Therapy | 6 participants |
| Previous Treatment Biliary: Chemotherapy | 7 participants |
| Previous Treatment Biliary: Radiotherapy | 3 participants |
| Previous Treatment Biliary: Surgery | 2 participants |
| Previous Treatment Biliary: Targeted therapy (sorafenib) | 0 participants |
| Previous Treatment Biliary: Y90 Radioembolization | 0 participants |
| Previous Treatment Hepatocellular: Chemotherapy | 3 participants |
| Previous Treatment Hepatocellular:Radiotherapy | 2 participants |
| Previous Treatment Hepatocellular:Surgery | 3 participants |
| Previous Treatment Hepatocellular:Targeted therapy (sorafenib) | 7 participants |
| Previous Treatment Hepatocellular: Y90 Radioembolization | 2 participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 9 / 25 |
Outcome results
Primary
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.
Time frame: Start of treatment until disease progression per RECIST criteria up to 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biliary | 16 Weeks Progression-free Survival | 4.7 months |
| Hepatocellular | 16 Weeks Progression-free Survival | 3.5 months |
Secondary
Overall Survival
Determine Overall Survival
Time frame: 18 Months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Biliary | Overall Survival | 6.7 months |
| Hepatocellular | Overall Survival | 5.7 months |
Secondary
Response Rate
Determine the Response Rate Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)
Time frame: 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biliary | Response Rate | Stable Disease | 7 participants |
| Biliary | Response Rate | Progressive Disease | 4 participants |
| Biliary | Response Rate | Complete Response or Partial Response | 0 participants |
| Hepatocellular | Response Rate | Complete Response or Partial Response | 0 participants |
| Hepatocellular | Response Rate | Stable Disease | 6 participants |
| Hepatocellular | Response Rate | Progressive Disease | 7 participants |