Hepatocellular Carcinoma, Liver Cancer
Conditions
Brief summary
This study is for people with cancer of the liver that cannot be completely removed by surgery. This study involves giving the drugs mitomycin-C and cisplatin, into an artery in the liver. Mitomycin-C is a drug that has been approved by the FDA to treat cancer of the stomach and pancreas. Mitomycin-C is a drug that causes cancer cells to die and prevents them from reproducing. Cisplatin is also a drug that has been approved by the FDA. Cisplatin is approved to treat cancer of the testes, ovaries, lung, esophagus, bladder, head and neck. Cisplatin is a drug that prevents cancer cells from reproducing. The purpose of this study is to see how long it takes subjects' tumor(s) to grow after receiving the study drugs. Another purpose of this study is to look at the side effects of this study therapy and how long subjects survive after receiving it. An additional purpose of this study is to see how well we can predict subjects' response to the study therapy, based on blood and tumor tissue tests. These tests will measure the levels of genes (the cell's blueprint) in subjects' tumors and blood. These genes affect how people's bodies react to the cancer drugs.
Interventions
DRUGmitomycin-c, cisplatin
Intra-arterial cisplatin 60 mg/m2 and mitomycin-C 12 mg/m2 every 8 weeks
Sponsors
University of Southern California
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable, histologically confirmed hepatocellular carcinoma with evident disease limited to liver. * Tissue from tumor must be available. This may be paraffin embedded tissue from previous biopsy/resection or if it is not available, a repeat biopsy must be performed. The requirement for biopsy may be waived if alpha-fetoprotein is greater than 500 ng/mL and in the investigators opinion not explained by a concurrent hepatic inflammatory process. * Patients must agree to have a 20 cc blood sample drawn in addition to routine labs with each cycle of chemotherapy. * Patients must have measurable disease. If prior radiation therapy was administered, measurable disease must be outside the radiation field. * Patients must have a Zubrod performance status of 0-2. * Patients must have a predicted life expectancy of at least 12 weeks. * Patients must have a pre-treatment granulocyte count (i.e., segmented neutrophils + bands) of greater than or equal to 1,500/mm3, a hemoglobin level of greater than or equal to 9 gm/dl, and platelet count greater than or equal to 50,000/mm3. The granulocyte requirement may be waived if in the investigator's opinion the lower count reflects hypersplenism with adequate bone marrow reserves. * Patients must have adequate renal function as documented by a calculated creatinine clearance ≥ 60. * Patients must have adequate hepatic function as documented by a serum bilirubin less than or equal to 2x the institutional upper limit of normal, regardless of whether patients have liver involvement secondary to tumor. Patients may not have ascites or the ascites must be responsive to diuretics.
Exclusion criteria
* Patients who have received prior chemotherapy for unresectable disease * Patients with any active or uncontrolled infection, including known HIV infection. (Patients with active hepatitis B will be placed on lamivudine. Patients with active hepatitis C will be eligible if liver tests qualify (5.1.9) * Patients with psychiatric disorders that would interfere with consent or follow-up. Pregnant or lactating women. Men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Patients with any other severe concurrent disease, which in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | Up to 2 years | A modified Response Evaluation Criteria In Solid Tumors (RECIST) will be used. The modification to RECIST is that although all lesions will be followed, only the treated lesions will be included in the assessment of response. Additionally, all lesions will be evaluated according to the following criteria: Presence of arterial enhancement: Yes or No. Complete Response (CR) = Absence of enhancing tumor areas, reflecting complete tissue necrosis. Partial Response (PR) = A decrease \> 50% of enhanced areas, reflecting partial tissue necrosis. Stable Disease (SD) = A tumor response between PR and PD. Progression (PD) = An increase \> 25% in the size of \> 1 measurable lesion(s) or the appearance of new lesions in the treated area (ie, specific segment or lobe of liver targeted by the intra-arterial infusion). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or Higher Toxicity | Up to 1 year | Toxicity will be assessed according to CTCAE version 3.0 |
Countries
United States
Participant flow
Recruitment details
Recruitment for this study opened in October 2004 and closed in February 2012. All subjects were seen and treated in the medical clinics at the University of Southern California.
Participants by arm
| Arm | Count |
|---|---|
| Cisplatin + Mitomycin-C CDDP 60mg/m2 + Mitomycin-C 12mg/m2
mitomycin-c, cisplatin: Intra-arterial cisplatin 60 mg/m2 and mitomycin-C 12 mg/m2 every 8 weeks | 76 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Death | 1 |
| Overall Study | Developed second malignancy | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Switched to alternative treatment | 8 |
| Overall Study | Treatment delayed too long | 4 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Cisplatin + Mitomycin-C |
|---|---|
| Age, Continuous | 61 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 23 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 29 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 76 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 44 / 76 |
| other Total, other adverse events | 75 / 76 |
| serious Total, serious adverse events | 51 / 76 |
Outcome results
Primary
Tumor Response
A modified Response Evaluation Criteria In Solid Tumors (RECIST) will be used. The modification to RECIST is that although all lesions will be followed, only the treated lesions will be included in the assessment of response. Additionally, all lesions will be evaluated according to the following criteria: Presence of arterial enhancement: Yes or No. Complete Response (CR) = Absence of enhancing tumor areas, reflecting complete tissue necrosis. Partial Response (PR) = A decrease \> 50% of enhanced areas, reflecting partial tissue necrosis. Stable Disease (SD) = A tumor response between PR and PD. Progression (PD) = An increase \> 25% in the size of \> 1 measurable lesion(s) or the appearance of new lesions in the treated area (ie, specific segment or lobe of liver targeted by the intra-arterial infusion).
Time frame: Up to 2 years
Population: Patients with measurable tumor who complete one cycle, or who terminate treatment for reasons of toxicity, or who progress prior to completion of one cycle, will be included in analysis of tumor response.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cisplatin + Mitomycin-C | Tumor Response | CR | 0 Participants |
| Cisplatin + Mitomycin-C | Tumor Response | PR | 7 Participants |
| Cisplatin + Mitomycin-C | Tumor Response | SD | 47 Participants |
| Cisplatin + Mitomycin-C | Tumor Response | PD | 11 Participants |
| Cisplatin + Mitomycin-C | Tumor Response | Inevaluable for Response | 11 Participants |
Secondary
Number of Participants With Grade 3 or Higher Toxicity
Toxicity will be assessed according to CTCAE version 3.0
Time frame: Up to 1 year
Population: All eligible patients who begin treatment are included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cisplatin + Mitomycin-C | Number of Participants With Grade 3 or Higher Toxicity | 75 Participants |