Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Primary Liver Cancer

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Doxorubicin

Liposomal doxorubicin

Chlorotrianisene

Liver Extracts

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

sorafenib: given 400 mg twice per day for as long as it is beneficial

sorafenib

LC Beads loaded with doxorubicin

Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period

LC Bead-TACE

This study will combine two therapies to treat patients with unresectable hepatocellular carcinoma; sorafenib, and drug eluting beads delivered intra-arterially. The purpose of the study is to establish the safety and the effectiveness of the combination therapy. The investigators hypothesize that the combination of the two therapies will not result in greater toxicities to patients than that expected for either therapy given alone.

Study of Sorafenib and Transarterial Chemoembolization (TACE) to Treat Hepatocellular Carcinoma

Phase II Trial of Sorafenib Combined With Doxorubicin Eluting Bead-Transarterial Chemoembolization (LC Bead-TACE) for Patients With Hepatocellular Carcinoma

Percentage of study patients surviving after one year from initial treatment analyzed with Kaplan-Meier curve.

Percentage of study patients surviving after three years from initial treatment analyzed with Kaplan-Meier curve.

Median overall survival stratified by Barcelona Clinic Liver Cancer (BCLC) staging as assessed by Kaplan-Meier estimator. Patients are grouped to stages A (early), B (intermediate), and C (advanced) according to stage of disease.

Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more. 50 patients were reviewed for toxicities for Cycle 1, and all 50 patients experienced at least one adverse event during this time period.

Treatment toxicities assessed by CTCAE v3.0 were stratified by cycle - patients on Cycle 1, and patients on Cycles 2-5 or more.

Efficacy as assessed by radiographic tumor response using the RECIST criteria at baseline and at 6 months post the initiation of treatment. 33 out of the original 50 patients were evaluable at this time point, with 17 out of the 50 exiting prior to 6 months or were not assessable by RECIST criteria.

Complete response (CR): Disappearance of all lesions targeted with therapy Partial Response (PR): at least 30% decrease in sum of longest diameter (LD) of targeted lesions Progressive Disease (PD): at least 20% increase in the sum of LD of targeted lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD

Efficacy as assessed by radiographic tumor response using the EASL criteria at baseline and at 6 months post the initiation of treatment.

Complete response (CR): 100% tumor necrosis Partial Response (PR): more than 50% tumor necrosis Progressive Disease (PD): increase in tumor enhancement by more than 25% Stable Disease (SD): Cases that do not qualify for one of the above criteria

Time to progression (TTP) - defined as the time from initiation of therapy to disease progression (radiological). Median TTP calculated for all subjects and stratified by Barcelona Clinic Liver Cancer (BCLC) staging.

46 patients out of 50 were reviewed for this outcome. 3 patients were excluded because they underwent liver transplantation and 1 patient was excluded for hepatic resection.

Overall survival was assessed with Kaplan-Meier estimates of survival, and the Mantel-Cox log-rank test was used to determine differences in survival.

All 50 patients were included in survival analyses as all 50 received at least one dose of sorafenib.

Overall survival was assessed with Kaplan-Meier estimates of survival, and the Mantel-Cox log-rank test was used to determine differences in survival.

Bayer

Biocompatibles UK Ltd

Yale University

single arm

sorafenib: sorafenib: given 400 mg twice per day for as long as it is beneficial

LC Bead-TACE: LC Beads loaded with doxorubicin

Doxorubicin loaded LC Beads: given intra-arterially into the liver, up to fours times in a 6 month period

Sorafenib and Drug Eluting Beads

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Jean-Francois Geschwind, MD

Anemia

Lymphopenia

Thrombocytopenia

Arrhythmia

Chest pain

Dissection

Embolus or coagulopathy

Hypertension

Lower extremity edema

Fatigue

Fever

Hand-foot skin reaction

Mucositis

Rash

Skin pain

Ascites

Anorexia

Diarrhea

Nausea or vomiting

Epistaxis or hemoptysis

Hematochezia

Hematoma

Tumor rupture

Elevated ALT level

Elevated AST level

Elevated AP level

Elevated amylase level

Elevated lipase level

Elevated INR level

Hyperbilirubinemia

Hypoalbuminemia

Infection

Dizziness

Headache

Encephalopathy

Nonspecific abdominal pain

Musculoskeletal pain

Right upper quadrant pain

Pain - other

Acute renal failure

Death (disease progression)

Safety Will be Assessed by Grading Toxicities Reported at Intervals Throughout the Study. Higher Grade Toxicities Will be Assessed for Their Degree of Relatedness to the Study Treatment.

Pancytopenia

Cholangitis

Liver abscess

39 patients were reviewed for toxicities for Cycle 2-5+. 11 patients out of the original 50 exited the study prior to Cycle 2.

Complete Response

Partial Response or Stable Disease

Progressive Disease

Disease control rate (CR + PR + SD)

33 out of the original 50 patients were evaluable for this outcome, with 17 out of the original 50 exiting prior to 6 months or were not assessable by RECIST criteria.

Efficacy Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) to Determine Response and Disease Control Rate

Partial Response

Stable Disease

32 out of the 50 patients had imaging assessable by EASL criteria at 6 months - 18 out of the original 50 had exited prior to this time point or did not have applicable imaging.

Efficacy Assessed by European Association for the Study of the Liver (EASL) Criteria to Determine Response and Disease Control Rate

Median TTP

Median TTP for BCLC stage A

Median TTP for BCLC stage B

Median TTP for BCLC stage C

Median TTP stratified by BCLC staging; 3 patients had BCLC stage A disease, 14 with stage B, and 29 with stage C.

Efficacy - Median TTP After Combination Treatment With Sorafenib and TACE

Efficacy - Overall Survival (OS) After Combination Treatment With Sorafenib and TACE

Median liver tumor burden >10%

Median tumor size > 10cm

ECOG performance status

BCLC stage

Efficacy - Factors Associated With Overall Survival (OS) After Combination Treatment With Sorafenib and TACE

All 50 patients were included in survival analyses as all 50 received at least one dose of sorafenib.

Estimated Percentage of Participants Surviving After One Year

Estimated Percentage of Participants Surviving After Three Year

BCLC A

BCLC B

BCLC C

50 total participants received sorafenib on trial. 3 were classified as BCLC A, 16 as BCLC B, and 31 as BCLC C.

Median Overall Survival OS Stratified by BCLC Criteria

Overall Study

Symptoms and General Pathology

Necrosis

correlation of necrosis with the deposition of beads

chemoembolization

KATERINA MALAGARI

The primary purpose of the study is to evaluate the distribution of radiopaque microspheres loaded with doxorubicin in the treatment of unresectable HCC. Prospective, single arm, open label, single centre, pilot study. All patients will undergo clinical follow-up. Twenty patients will be enrolled.

The primary purpose of the study is to evaluate the distribution of radiopaque microspheres loaded with doxorubicin in the treatment of unresectable HCC. Prospective, single arm, open label, single centre, pilot study. All patients will undergo clinical follow-up. Twenty patients will be enrolled. Primary endpoint : Local response (evaluated with CT and MRI at 4 to 6 weeks post each procedure and at 6 months according to mRECIST) in patients with intermediate-stage HCC following chemoembolisation with radiopaque bead. Secondary endpoints include: 1) Better definition of end point of embolization for drug eluting beads : Ability to achieve near-stasis during chemoembolisation procedure in the tumour feeding vessels using intra-procedural imaging feedback from the radiopaque bead (early visualization of non target embolization 2) Total dose needed for tumor devascularization 3)Distribution of radiopaque beads and correlation with necrosis and adverse events

DC Bead LUMI (TM) Loaded With Doxorubicin for Intermediate Hepatocellular Carcinoma (HCC)

Correlation of Necrosis With DC Bead LUMI (TM) Distribution

CT and MRI images will be stored anonymously by giving each patient a code number

Local response following chemoembolisation

dose required for tumor devascularization

correlation between imaging and tumor necrosis

Malagari Katerina

ASSOCIATE PROFESSOR

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Irinotecan

Topoisomerase I Inhibitors

For unilobar disease, two treatments will be planned, separated by four weeks. For bilobar disease, there will be four treatments planned, alternating between right and left lobe, separated by 2 weeks duration.

DEBIRI

Kiang Hiong Tay, MBBS FRCR

Background

Hepatic metastases of colorectal cancer (MCC) is quite common and is a major source of morbidity and mortality. There has been evidence to show that hepatic arterial chemoembolisation using DC beads (drug eluting beads, 100-300μm) loaded with irinotecan (DEBIRI) showed improved overall survival when compared to systemic therapy (FOLFIRI), but being larger they have their limitations.

New 70-150μm beads are recently available and currently there is limited data concerning its use. Safety of these beads have not been tested in local patients.

Hypothesis / Aim To study the safety and pharmacokinetics of the smaller 70-150μm DEBIRI in a pilot study of 5 patients. The smaller 70-150μm beads will be able to deliver a more consistent and higher dose to tumoral tissue with a smaller systemic dose. Being smaller and less embolic, it will also be better tolerated. Patients will also be genotyped for their UGT1A1\*28 and UGT1A1\*6 polymorphism status as the latter genotypes are associated with decreased clearance of irinotecan and SN-38 in Asian patients.

Methods Single centre, pilot study, prospectively recruiting 5 patients with unilobar disease, refractory to systemic chemotherapy

The primary endpoints:

1. establish safety and toxicity profile of the irinotecan loaded DEBIRI beads
2. establish pharmacokinetics and systemic exposure of irinotecan and its active metabolite, SN-38.

The secondary outcome measurements:

1. the incidence and severity of adverse events, liver function parameters and laboratory abnormalities;
2. response rate,
3. progression free survival
4. overall survival

Clinical Significance

This treatment modality has the advantage of directly delivering irinotecan to the liver metastases from colorectal cancer. This local mode of drug delivery may result in a higher intratumoral drug concentration and rapid tumour shrinkage leading to downstaging of the hepatic metastatic lesions. These therapeutic outcomes may also downstage patients to hepatic resection.

1. Recruitment:

   Suitable potential subjects will be identified, namely those who have failed first or second line chemotherapy agents.
2. Liver biopsy Right before the 1st transarterial chemoembolisation procedure, the liver metastases will be biopsied under ultrasound or CT guidance by the IR with a 18G core biopsy needle. Tissue will be sent for histological analysis as well as stored for molecular studies with NCCS.
3. Transarterial chemoembolisation procedure (DEBIRI TACE):

100mg of irinotecan will be loaded into the DEB solution at least 2 hours before the procedure by the pharmacy.

Diagnostic angiography (DSA) will performed under fluoroscopic guidance, most commonly via right groin puncture. Using dedicated catheters, arterial supply of the liver and the tumour involved segments will be determined. A solution of 75-150 μm DEBIRI mixed with non-ionic contrast medium (1:1) will be injected into the artery feeding the metastases.

For unilobar disease, two treatments will be planned, each of them with a maximum of 100mg irinotecan loaded in into the DEB, separated by four weeks. Intravenous fentanyl will be administered for procedural pain relief. Post procedural pain relief medications will be given as deemed necessary by the physician.

For bilobar disease, there will be four treatments planned, alternating between the right and left lobe, separated by 2 weeks duration, each of them with a maximum of 100mg irinotecan loaded into the DEB. Intravenous fentanyl will be administered for the procedural pain relief. Post procedural pain relief will be given as deemed necessary by the physician.

Technical success is defined as delivery of all the DEBIRI or when stasis has been reached in the hepatic artery.

Patients will be expected to stay in the hospital for at least a day for monitoring of adverse events, after which they will be followed up in the clinic.

Procedures will be delayed at the physician's discretion should:

* Liver function tests and bilirubin 5-folds more than the normal values
* Absolute neutrophil count of less than 1500 cells/µL
* Platelet count of less than 100,000/µL
* Severe adverse events.

Should the patient development significant extrahepatic metastases at any time during the course of the trial, the referring clinician may choose to stop the trial and/or offer patients other treatment modalities e.g. radiotherapy or further lines of chemotherapy.

4)Follow up:

Patients will be expected to stay in the hospital for at least a day for monitoring of adverse events, after which they will be followed up in the clinic. All patients will be seen in the clinical 1 week after each procedure with FBC and LFT determinations being performed. They will then be seen in the clinic 1 week prior to their next procedure.

Patients will be followed up 3 months after the last procedure. Serum drug levels and adverse events will be monitored. Imaging response will be determined by modified RECIST criteria.

A CT scan will be performed 1 month and 3 months after completion of the procedure to evaluate treatment response. Tumor response will be determined using modified RECIST criteria (7).

5)Pharmacokinetics of irinotecan Blood samples (3 mL) for pharmacokinetic analyses will be collected at the following time points after administration of the first dose on day 1: 0 minutes (pretreatment blank), 1h, 2h, 4h, 8h and 24h hours postinfusion. Blood will be immediately centrifuged at 2000 g for fifteen minutes, and the plasma transferred to a 1.5 mL polypropylene tube and stored at -20°C. Irinotecan and its metabolites, SN-38 and SN-38G will be assayed using LC-MS/MS method. The purpose of performing pharmacokinetics would be to quantitate the AUC of irinotecan, SN-38 and SN-38G in plasma.

6)Pharmacogenetics Analysis Pharmacogenetic analyses for UGT1A1\*28 and UGT1A1\*6 will be done in all patients prior to administration of irinotecan in accordance with previously published studies by our laboratory (6-9). All participating patients will have venous blood samples (3 mL) drawn for genomic DNA collection in EDTA tubes and labeled with the patient's identification number, date of collection, age, ethnic group and sex.

Unused DNA samples from patients enrolled in the genotyping arm will be stored at -20°C for future pharmacogenetic investigations related to irinotecan research. Patients will be informed and written consent will be taken from them.

8)Potential Risks and benefits

Anticipated benefits:

1. Reduction in the size of the liver lesions hence prolonging survival
2. Meeting criteria for liver resection for metastases

Possible risks:

Adverse events related to procedure include:

1. Access site injuries
2. Hepatic artery injury
3. Non target embolization resulting in acute cholecystitis, peptic ulcer, pancreatitis etc.
4. Post embolization syndrome, manifested by fever, malaise, right upper quadrant pain, nausea, and vomiting
5. Hepatic abscess and biloma
6. Biliary strictures
7. Liver failure

Adverse events related to irinotecan include:

1. Diarrhea
2. Vomiting
3. Leucopenia
4. Anemia
5. Thrombocytopenia

7. Abdominal pain 8. Fever

All chemotherapeutic toxicities will be graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC version 3).

Hematological Dose Limiting Toxicity (DLT) is defined as follows: grade 4 neutropenia of \>7 days duration, neutropenic fever, grade 4 anemia or grade 3-4 thrombocytopenia that occurs during the first cycle of treatment.

9)Adverse events

Using Health Science Authority's Safety Reporting for Clinical Trials (June 2011), a serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose

1. Results in death
2. Is life-threatening
3. Requires inpatient hospitalisation or prolongation of existing hospitalization
4. Results in persistent or significant disability/incapacity, or
5. A congenital anomaly/birth defect.

An adverse event is defined as: Any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Adverse events related to procedure include:

1. Access site injuries
2. Hepatic artery injury
3. Non target embolization resulting in acute cholecystitis, peptic ulcer, pancreatitis etc.
4. Post embolization syndrome, manifested by fever, malaise, right upper quadrant pain, nausea, and vomiting
5. Hepatic abscess and biloma
6. Biliary strictures
7. Liver failure

All chemotherapeutic toxicities will be graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC version 3).

Hematological Dose Limiting Toxicity (DLT) is defined as follows: grade 4 neutropenia of \>7 days duration, neutropenic fever, grade 4 anemia or grade 3-4 thrombocytopenia that occurs during the first cycle of treatment.

Non-hematologic DLT is defined as any grade 3 or grade 4 non-hematologic toxicity that occurs during the first cycle of treatment.

Toxicities will be classified as related to the study drug unless they were attributable to either underlying tumour progression, concurrent medical condition or a concomitant medication. Any unusual toxicities must be reported to the Principal Investigator.

10)Safety Monitoring Plan

Data monitoring

- The principle and co-investigators.

Safety monitoring

* The medical practitioner performing the procedure will be overall responsible for the patient prior to, during and after the intervention.
* The monitoring nurse in the recovery area and the circulating nurse during the procedure will assist the medical practitioner in recording and monitoring the patient's parameters.
* All complications and adverse events will be recorded in the CRFs and the patient will be followed up.

In the event of any SAE's regardless of the causality of the event, the investigator will notify to the IRB of SingHealth. The reporting timelines are:

Urgent Reporting: All problems involving local deaths should be reported immediately within 24 hours after first knowledge by the investigator.

Expedited Reporting: All other SAE must be reported as soon as possible but not later than 7 calendar days after first knowledge by the investigator.

A Data \& Safety Monitoring Committee (DSMC) comprising of co-principal investigators from the participating centres, will monitor the safety data .

If the DSMC have any safety concerns, they may make written recommendations to the primary PI and the IRB of SingHealth to modify or terminate the study following discussions with the primary PI. The final decision on the termination of the study will be made by SGH after consulting with IRB and HSA about the safety findings or concerns.

11)Confidentiality of Data and Patient Records

Data required according to the protocol will be recorded on the CRFs as soon as possible.

* Entries must be made with a ballpoint pen and written legibly. No pencils or correction fluids will be used.
* Relevant information will be documented into the patient's hospital files (either paper or electronic records).
* Necessary corrections will be entered by the investigator or, if appropriate, by an authorized member of the investigator's staff in the following manner: The wrong entry will be crossed out, although it must remain legible, and the correct entry will be placed next to it. All corrections will be initialed and dated. For corrections concerning adverse events or the primary variable, a reason for any alteration must be provided.
* Any documents related to the study must be archived at the study site or in a central archive. This includes the careful listing of the identities of the patients involved in the study. This list and the signed informed consent statements are key documents in the files to be stored by the investigator.
* Patient (hospital) files will be archived according to local regulations. All documents related to the study must be retained until at least 15 years after the end of the study. At the end of this period, the investigator is to obtain permission from the relevant authorities (IRB) before any documents are destroyed.

Pilot Study to Assess the Safety and Pharmacokinetics of 70-150μm Drug Eluting Beads Loaded With Irinotecan (DEBIRI).

Pilot Study to Assess the Safety and Pharmacokinetics of 70-150μm Drug Eluting Beads Loaded With Irinotecan (DEBIRI) in the Treatment of Hepatic Colorectal Metastases

By looking at the number of patients with adverse events according to Health Science Authority's Safety Reporting for Clinical Trials (June 2011)

Singhealth Foundation

Singapore General Hospital

The control arm will be of the patients that have been treated historically in the centers with conventional TACE (that is Lipiodiol plus doxorubicin).

HCC patients will receive chemoembolization (TACE) using DC beads containing Doxorubicin. The objective is to give 2 vials of DC Bead (2ml per vial) loaded with 70-75mg of Doxorubicin per vial (Each vial contain 2ml of DC Bead, thus doxorubicin concentration will be of 35-37.5mg per ml of DC Beads)

DebDox TACE

Jin Wook Chung, MD

In unresectable hepatocellular carcinoma, TACE using Lipiodol/anti cancer agent emulsion is the standard treatment and reported as a significantly better treatment through randomized comparison study like Llovet, etc. than conservative treatment. Recently, doctors do transarterial chemoembolization with drug-eluting bead, and it is proved less side effect and better efficacy than conventional TACE using Lipiodol in Precision V study by Dr. Lammer, etc. But, it could not defined improved survival rate as expected. This study's purpose is evaluating treatment efficacy, survival rate and safety of TACE using drug eluting bead by comparing to conventional TACE using doxorubicin/Lipiodol emulsion for unresectable hepatocellular carcinoma.

Comparison Between Drug-Eluting Bead vs conventional TACE.

Drug-eluting bead group : TACE using DC bead loading Doxorubicin. Conventional TACE group : TACE using Doxorubicin/Lipiodol emulsion and gelatin sponge/PVA particle.

cTACE group was chosen by concurrent matched patients (age, sex, tumor stage, and Child-Pugh class are matched)

5.7 Technically considerable aspects of DC bead TACE group

1. Planned dose of doxorubicin. Each vial of DC Bead (2 ml of beads) should be loaded with 70-75 mg doxorubicin (loading dose, 35-37.5 mg doxorubicin / ml of beads).

   * Early-stage HCC. As a general rule, each single treatment should include a planned dose of up to 75 mg doxorubicin loaded into one vial of DC Bead.
   * Medium-sized (less than 8cm) / multinodular HCC. As a general rule, each single treatment should include a planned dose of up to 150 mg doxorubicin loaded into two vials of DC Bead.
   * In large tumors (more than 8cm), even if unilobar, the separate treatment including two sessions 2-4 weeks apart is recommended.
   * In bilobar tumors, both hepatic lobes should be treated in separate treatment sessions 2-4 weeks apart, in the absence of complications requiring a longer time interval between the two sessions. Obtaining confirmation that the liver enzymes did return to baseline before performing the second treatment session is recommended.
2. Choice of DC Bead size. Use of 100-300μm beads is recommended for a standard procedure. However, individual patient and tumor characteristics, particularly the identification of arterio-venous shunting, should be taken into account when the safety of the treatment and the choice of DC Bead size are determined.

   * In the case of significant arterio-portal or hepatic venous shunting, embolization of the shunt with gelfoam pledgets is recommended before proceeding with DEBDOX. Confirmation that the shunt is no longer present must be obtained before DEBDOX can safely be performed. But, this study excludes the patients with arterio-portal or hepatic venous shunts.
   * In large tumors, hepatic arterial flow does not reach 'near stasis' after injection of 2 vial of 100-300 μm DC beads. The recommendation is following: 2 vials of the 100-300 μm DC beads is best and then repeat 2 weeks later if the patient is doing well clinically.
3. DC Bead dilution. Mix loaded DC Bead with a non-ionic contrast medium. At least 5-10 ml of non-ionic contrast should be used per 1 ml of DC Bead (i.e., 10-20 ml are required to dilute one vial of DC Bead) prior to injection.
4. Catheter positioning. A superselective (i.e., segmental or subsegmental) approach should be used whenever possible by using a microcatheter. Use of 3D / MPR obtained from C-arm rotational angiography with a flat-panel detector system (cone-beam CT) is recommended, if available, to improve the accuracy in identifying tumor-feeding arteries. Such imaging allows for accurate targeting of the tumor. In addition, repeat cone beam CT should be performed after successful delivery of the DC Bead to confirm adequate targeting and saturation of the tumor(s).

   * Segmental / subsegmental approach. Place the microcatheter into the segmental / subsegmental vessel feeding the tumor as distally as possible - but avoiding wedging the catheter to avoid reflux along the catheter shaft. Flow within the artery must be preserved.
   * Lobar approach. Place the catheter as selectively as possible in the right or left hepatic artery. Pay attention to identifying the origin of the cystic artery as well as other arteries supplying flow to extra-hepatic organs such as the right gastric artery, para-esophageal or omental vessels among others. If identified, these vessels must be either embolized using coils or avoided by placing the catheter tip well beyond the origin of these vessels. In addition, forward flow into the desired vessel must be maintained as inadvertent administration of even a few DC Beads into these extra-hepatic vessels could have dire consequences.
5. Injection. The injection must be very slow. An injection rate of 1 ml of the contrast agent - DC Bead suspension per minute is recommended. Thus, it takes 10-20 minutes to infusion 1 vial of DC bead. Care should be taken to avoid sedimentation of the beads in the syringe by rotating the syringes or using a 3-way stopcock to gently suspend the beads in the solution.
6. Embolisation endpoint. Injection should be continued until "near stasis" is observed in the artery directly feeding the tumor (i.e., the contrast the contrast column should clear within 2-5 heart beats). At that point, injection should be stopped - regardless of the amount of beads that have been actually administered - to avoid reflux of embolic material. Once the embolisation endpoint has been achieved, no additional embolic material should be injected. If the "near stasis" endpoint is not obtained after injection of the scheduled volume of beads, no additional embolization should be performed. This patient is likely to benefit from a second course after imaging follow-up.
7. extrahepatic collateral vessels. In principle, DC bead is used for collateral arterial circulation (inferior phrenic artery, internal mammary artery, intercostal artery), but doctors can do bland embolization (PVC particle, gelatin sponge) based on their judgement.
8. Repeated treatment. In principle, treatment with the same method is repeated for every 2 - 3 months as tumor progression is observed. But, even if tumor progression is not observed, the treatment can be repeated for tumor repression. If there is no tumor left, contrast enhancement CT or MRI can be performed for every 2- 3 months as follow up.

5.8. Dose in study Dose of DC bead, anti cancer agent for TACE dose is decided by tumor size. So, this study just set up the maximum dose.

Drug-eluting bead group DC bead : 2 bottles DC bead absorbs 70-75mg per bottle. Doxorubicin loading to DC bead needs to be done 1.5 hours before using. The size of DC bead is 100-300 micrometer, and it can be used up to 2 bottles.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Sorafenib and Transarterial Chemoembolization (TACE) to Treat Hepatocellular Carcinoma	NCT00844883	Hepatocellular ... Hepatoma	sorafenib LC Bead-TACE	18 Years -	Yale University
DC Bead LUMI (TM) Loaded With Doxorubicin for Intermediate Hepatocellular Carcinoma (HCC)	NCT03474354	Hepatocellular ... Chemoembolizati...	chemoembolizati...	18 Years - 88 Years	University of Athens
Pilot Study to Assess the Safety and Pharmacokinetics of 70-150μm Drug Eluting Beads Loaded With Irinotecan (DEBIRI).	NCT02350400	Colorectal Canc...	DEBIRI	21 Years -	Singapore General Hospital
Drug-eluting Bead in Hepatocellular Carcinoma	NCT01332669	Hepatocellular ...	DebDox TACE	20 Years -	Seoul National University Hospital
Drug-eluting Bead in Hepatocellular Carcinoma	NCT01332669	Hepatocellular ...	DebDox TACE	20 Years -	Seoul National University Hospital

Spots Global Cancer Trial Database for drug eluting beads