Unresectable Intrahepatic Cholangiocarcinoma
Conditions
Keywords
LC Bead, Irinotecan, ONCOZENE BEAD
Brief summary
The purpose of this study is to find out if the combination of trans-arterial chemoembolization (LC or ONCOZENE BEAD) plus infusional chemotherapy is safe and more effective than just receiving the infusional chemotherapy alone.
Interventions
Sponsors
Study design
Eligibility
Inclusion criteria
Inclusion: * Patients over 18 years of age, of any race or sex, who have histologic and radiologic evidence of intrahepatic cholangiocarcinoma, who have been deemed unresectable by an experienced hepatic surgeon, and who are able to give informed consent, will be eligible * Patients with at least one measurable liver tumor, with size \> 1cm (modified RECIST criteria) * Patients with liver-dominant disease defined as ≥80% tumor burden confined to the liver * Non-pregnant with an acceptable contraception in premenopausal women. * Hematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 75 x109/L, INR ≤1.3 (patients on therapeutic anticoagulants are not eligible if they can not stop there anti-coagulation prior to DEBIRI and meet INR criteria) * Adequate liver function as measured by: Total bilirubin ≤ 2.0 mg/dl, * Adequate renal function (creatinine ≤ 2.3 mg/dl) * Women of child bearing potential and fertile men are required to use effective contraception (negative serum βHCG for women of child-bearing age) * Signed, written informed consent * Less than 70% of liver parenchymal tumor replacement Exclusion: * Patient eligible for curative treatment (i.e. resection or tumor ablation). * Active bacterial, viral or fungal infection within 72 hours of study entry * Women who are pregnant or breast feeding * ECOG Performance Status score of \>3 * Life expectancy of \< 3 months * Allergy to contrast media that cannot be managed with standard care (e.g. steroids), making magnetic resonance imaging (MRI) or computed tomography (CT) contraindicated * Presence of another malignancy with the exception of cervical carcinoma in situ and stage I basal or squamous cell carcinoma of the skin. * Any contraindication for hepatic embolization procedures: * Large shunt as determined by the investigator (pretesting with TcMMA not required) * Severe atheromatosis vascular disease that precludes arterial cannulization * Hepatofugal blood flow * Main portal vein occlusion (e.g. thrombus or tumor) * Other significant medical or surgical condition, or any medication or treatment, that would place the patient at undue risk and that would preclude the safe use of chemoembolization or would interfere with study participation * Patients with prior contraindications for the use of irinotecan, gemcitabine, or cisplatin * Patients who have received prior systemic therapy with either irinotecan, gemcitabine, or cisplatin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response (Overall Response = Complete Response + Partial Response + Progressive Disease + Stable Disease) | Assessed at 2, 4 and 6 months. 6 months reported. | Tumor response will be determined using Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Response will be classified as: Complete Response - disappearance of all lesions; Partial Response - at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter or 30% reduction in arterial enhancement; Progressive Disease - at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest longest diameter recorded since start of treatment or appearance of one or more new lesions greater than 1cm in size; Stable Disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 4.5 Years | Long-term follow-up will occur every 3-4 months for up to one year after discontinuation of active study treatment. Subjects who have completed the long-term follow-up period will be monitored every 3 - 6 months until evidence of progression of disease. Once there is progression of disease subjects will be followed for overall survival by telephone or standard physician follow-ups as per standard of care until death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo
LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo | 24 |
| Randomization to Gem-Cis or Gem-Carbo Gem-Cis or Gem-Carbo alone
Gem-Cis or Gem-Carbo | 22 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Screen Fail Post Randomization | 1 | 2 |
Baseline characteristics
| Characteristic | Randomization to Gem-Cis or Gem-Carbo | Total | Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 18 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 28 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 40 Participants | 21 Participants |
| Sex: Female, Male Female | 13 Participants | 26 Participants | 13 Participants |
| Sex: Female, Male Male | 9 Participants | 20 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 17 / 24 | 16 / 22 |
| other Total, other adverse events | 24 / 24 | 19 / 22 |
| serious Total, serious adverse events | 21 / 24 | 19 / 22 |
Outcome results
Tumor Response (Overall Response = Complete Response + Partial Response + Progressive Disease + Stable Disease)
Tumor response will be determined using Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Response will be classified as: Complete Response - disappearance of all lesions; Partial Response - at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter or 30% reduction in arterial enhancement; Progressive Disease - at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest longest diameter recorded since start of treatment or appearance of one or more new lesions greater than 1cm in size; Stable Disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since start of treatment.
Time frame: Assessed at 2, 4 and 6 months. 6 months reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo | Tumor Response (Overall Response = Complete Response + Partial Response + Progressive Disease + Stable Disease) | 24 participants |
| Randomization to Gem-Cis or Gem-Carbo | Tumor Response (Overall Response = Complete Response + Partial Response + Progressive Disease + Stable Disease) | 22 participants |
Overall Survival
Long-term follow-up will occur every 3-4 months for up to one year after discontinuation of active study treatment. Subjects who have completed the long-term follow-up period will be monitored every 3 - 6 months until evidence of progression of disease. Once there is progression of disease subjects will be followed for overall survival by telephone or standard physician follow-ups as per standard of care until death.
Time frame: 4.5 Years
Population: All randomized subjects who receive at least one cycle of intravenous chemotherapy or LC or ONCOZENE beads loaded with irinotecan. Subjects will be grouped according to their randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo | Overall Survival | 33.7 Months |
| Randomization to Gem-Cis or Gem-Carbo | Overall Survival | 12.6 Months |