Hepatocellular Carcinoma, Hepatoma, Liver Cancer
Conditions
Keywords
Liver Cancer, Hepatoma, 07-099
Brief summary
The purpose of this study is to evaluate the effect of blocking the blood vessels to the tumor in your liver with small beads alone (Bead Block) versus blocking them with the same bead that contains and releases doxorubicin (a chemotherapy agent). The reason for the study is to see if adding doxorubicin kills more tumor than would be killed by just blocking the blood supplying the tumor. The chemotherapy, doxorubicin, has been used for many years to treat patients with cancer. This procedure to block the blood vessels is called embolization. Embolization is a common treatment for patients with liver cancer who cannot have surgery. The investigators are comparing the standard treatment (using the small beads alone) with another that should be at least as good, but possibly better (with the addition of the drug, doxorubicin). There is no guarantee that the new treatment is better and it is possible that there might be more side effects (related to the doxorubicin) than what is seen with the standard treatment.
Detailed description
Biocompatibles LC Bead (also known as DC Bead in Asia & Europe) microspheres are preformed soft, deformable microspheres that may be loaded with doxorubicin and used to occlude blood flow to a cancerous tumour. LC Bead microspheres consist of a macromere derived from PVA. The fully polymerized microsphere is approximately 90% water and is compressible to approximately 30% by diameter. The microspheres can be delivered through conventional catheters (4-5Fr) or micro-catheters in the 2-3Fr range. These microspheres, like all agents used for arterial embolization, are mixed with radiographic contrast prior to administration in order to allow for fluoroscopic control of the embolization procedure.
Interventions
DEVICEBead Block microspheres
Bead Block (Beads) microsphere, 100-300 micron with additional larger size beads as necessary to achieve stasis
OTHERBead + Dox Arm
Bead + Dox Arm: Hepatic arterial embolization with 100-300 micron drug eluting microspheres (LC Bead) loaded with 150 mg Doxorubicin, followed by embolization with Bead Block microspheres (100-300 micron and larger size beads as necessary) until stasis is evident.
Sponsors
Columbia University
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with a confirmed diagnosis of HCC according to EASL criteria for diagnosis; who is not a surgical resection candidate, or refuses surgery * Patient must be 18 years of age or older * Patient must be Okuda stage I or II * Patient must have an ECOG performance status of 0 or 1 * No prior chemotherapy or biotherapy within 4 weeks of scheduled embolization, with all toxicities, if any, resolved to grade \< than or = to 1 * Patient must have the following laboratory values confirmed within 14 days of registration: * Creatinine ≤ than or = to 2.0 the institution ULN * Platelets ≥ than or = to 50,000/mm3 * INR ≤ than or = to 2.0 for patients who are not on Coumadin * aPTT \< or = to twice control * Bilirubin \< 3 mg/dl * WBC \> 3000 cells/mm3 * ANC \> 1500 cells/mm3 * Negative serum pregnancy test (Female of childbearing potential only)
Exclusion criteria
* Patient has another primary tumor, with the exception of conventional basal cell CA, superficial bladder cancer, melanoma in situ, or treated prostate cancer currently without biochemical or radiographic evidence of active disease * Women who are pregnant or lactating * Patient previously treated with doxorubicin * Contraindication to angiography/embolization including: patients who cannot receive contrast 1.Severe allergic reaction to contrast despite pre-medication, 2. poor renal function; 3.Lack of arterial access (eg femoral artery occlusion); 4. other, based on judgment of the investigator * Patient has already undergone hepatic arterial embolization for the hepatocellular cancer for which they are currently being evaluated * Patient has received prior radiotherapy for the hepatocellular cancer for which they are currently being evaluated * Patient has had previous local-regional treatment of the current target tumor volume * Patient who cannot have CT scan * Patient at very high risk for post-embolization hepatic failure: 1. Child's C cirrhosis, 2. \> 75% liver replaced by tumor * Cardiac exclusion for: 1. Myocardial infarction within 90 days of study, 2. uncontrolled arrhythmia, 3. LVEF \< 50% for patients randomized to receive LC Bead * Patients with tumors exhibiting characteristics considered contra-indications to particle embolization, including: 1. collateral vessel pathways potentially endangering normal territories during embolization, 2. arteries supplying tumor not large enough to accept LC Bead or Bead Block, 3. Presence of arterial to systemic venous shunts, 4. Presence of arterial to pulmonary vascular shunts
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response to Treatment by RECIST Criteria | 2 to 3 weeks | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Evaluated for Toxicity | 1 year | Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 3.0. |
| Progression Free Survival | 1 year | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Overall Survival | 1 year | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bead Arm Hepatic arterial embolization with Bead Block microspheres, beginning with 100 - 300 micron beads, and using larger particles if necessary until stasis is evident.
Bead Block microspheres: Bead Block (Beads) microsphere, 100-300 micron with additional larger size beads as necessary to achieve stasis | 51 |
| Bead + Dox Arm Hepatic arterial embolization with 100-300 micron drug eluting microspheres (LC Bead) loaded with 150 mg Doxorubicin, followed by embolization with Bead Block microspheres (100-300 micron and larger size beads as necessary) until stasis is evident.
Bead + Dox Arm: Bead + Dox Arm: Hepatic arterial embolization with 100-300 micron drug eluting microspheres (LC Bead) loaded with 150 mg Doxorubicin, followed by embolization with Bead Block microspheres (100-300 micron and larger size beads as necessary) until stasis is evident. | 50 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Bead Arm | Total | Bead + Dox Arm |
|---|---|---|---|
| Age, Continuous | 68 years | 67 years | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 51 Participants | 101 Participants | 50 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 41 Participants | 79 Participants | 38 Participants |
| Region of Enrollment United States | 51 Participants | 101 Participants | 50 Participants |
| Sex: Female, Male Female | 14 Participants | 23 Participants | 9 Participants |
| Sex: Female, Male Male | 37 Participants | 78 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 48 / 51 | 47 / 50 |
| other Total, other adverse events | 33 / 51 | 28 / 50 |
| serious Total, serious adverse events | 48 / 51 | 47 / 50 |
Outcome results
Primary
Response to Treatment by RECIST Criteria
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 2 to 3 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bead Arm | Response to Treatment by RECIST Criteria | Participants With Response | 3 Participants |
| Bead Arm | Response to Treatment by RECIST Criteria | Participants Without Response | 48 Participants |
| Bead + Dox Arm | Response to Treatment by RECIST Criteria | Participants With Response | 3 Participants |
| Bead + Dox Arm | Response to Treatment by RECIST Criteria | Participants Without Response | 47 Participants |
Secondary
Number of Participants Evaluated for Toxicity
Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 3.0.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bead Arm | Number of Participants Evaluated for Toxicity | 51 Participants |
| Bead + Dox Arm | Number of Participants Evaluated for Toxicity | 50 Participants |
Secondary
Overall Survival
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bead Arm | Overall Survival | Alive | 3 Participants |
| Bead Arm | Overall Survival | Dead | 48 Participants |
| Bead + Dox Arm | Overall Survival | Alive | 3 Participants |
| Bead + Dox Arm | Overall Survival | Dead | 47 Participants |
Secondary
Progression Free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Bead Arm | Progression Free Survival | 6.2 months | Standard Deviation 0.11 |
| Bead + Dox Arm | Progression Free Survival | 2.8 months | Standard Deviation 0.11 |