DELTIC: Drug-Eluting Bead, Irinotecan Therapy for Unresectable Intrahepatic Cholangiocarcinoma w/Concomitant Gemcitabine and Cisplatin or Carboplatin

• Sponsor: Robert C. Martin (Other)
• Overall Status: Completed
• CT.gov ID: NCT01648023
• Collaborator: University of Louisville (Other)
• Enrollment: 49
• Location: 1
• Arms: 2
• Duration (Months): 86
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Unresectable Intrahepatic Cholangiocarcinoma	Device: LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo; Drug: Gem-Cis or Gem-Carbo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparative, Prospective, Open-labeled, Randomized Phase II Study of Cisplatin or Carboplatin With Gemcitabine in Combination With Irinotecan-loaded Beads (LC or ONCOZENE) Versus Cisplatin or Carboplatin With Gemcitabine Alone in the Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jan 1, 2019
• Actual Study Completion Date: Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Randomization to LC OR ONCOZENE Bead with Gem-Cis or Gem-Carbo Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo	Device: LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo
Active Comparator: Randomization to Gem-Cis or Gem-Carbo Gem-Cis or Gem-Carbo alone	Drug: Gem-Cis or Gem-Carbo

Outcome Measures

Primary Outcome Measures

1. Overall Survival [2 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Louisville	Louisville	Kentucky	United States	40202

Sponsors and Collaborators

• Robert C. Martin
• University of Louisville

Investigators

• Principal Investigator: Robert Martin, MD, PhD, University of Louisville

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 30, 2017

More Information

Publications

None provided.

• Responsible Party: Robert C. Martin, Professor, University of Louisville
• ClinicalTrials.gov Identifier: NCT01648023
• Other Study ID Numbers: 11-0181
• First Posted: Jul 24, 2012
• Last Update Posted: Jan 13, 2022
• Last Verified: Dec 1, 2021

• Keywords provided by Robert C. Martin, Professor, University of Louisville: LC Bead; Irinotecan; ONCOZENE BEAD
• Additional relevant MeSH terms: Cholangiocarcinoma

Study Results

Participant Flow

Arm/Group Title	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo
Arm/Group Description	Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
Period Title: Overall Study
STARTED	25	24
COMPLETED	24	22
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo	Total
Arm/Group Description	Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo	Total of all reporting groups
Overall Participants	24	22	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 62.5%	13 59.1%	28 60.9%
>=65 years	9 37.5%	9 40.9%	18 39.1%
Sex: Female, Male (Count of Participants)
Female	13 54.2%	13 59.1%	26 56.5%
Male	11 45.8%	9 40.9%	20 43.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 4.2%	0 0%	1 2.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 8.3%	3 13.6%	5 10.9%
White	21 87.5%	19 86.4%	40 87%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	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	2 years

Outcome Measure Data

Analysis Population Description

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/Group Title	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo
Arm/Group Description	Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
Measure Participants	24	22
Median (Full Range) [Months]	30.3	11.2

Adverse Events

Time Frame	Approximately 1 year
Arm/Group Title	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo		Randomization to Gem-Cis or Gem-Carbo
Arm/Group Description	Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo		Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
All Cause Mortality
	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo		Randomization to Gem-Cis or Gem-Carbo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/24 (70.8%)		16/22 (72.7%)
Serious Adverse Events
	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo		Randomization to Gem-Cis or Gem-Carbo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/24 (87.5%)		19/22 (86.4%)
Blood and lymphatic system disorders
Anemia	1/24 (4.2%)		0/22 (0%)
Leukocytosis	1/24 (4.2%)		1/22 (4.5%)
Neutropenia	1/24 (4.2%)		1/22 (4.5%)
Neutropenic Fever	2/24 (8.3%)		0/22 (0%)
Thrombocytopenia	2/24 (8.3%)		1/22 (4.5%)
Cardiac disorders
Acute Cardiac Injury	0/24 (0%)		1/22 (4.5%)
Acute Cardiorespiratory Distress	0/24 (0%)		1/22 (4.5%)
Acute Myocardial Infarction	1/24 (4.2%)		0/22 (0%)
Congestive Heart Failure	1/24 (4.2%)		0/22 (0%)
Hypertension	2/24 (8.3%)		1/22 (4.5%)
Myocardial Infarction	0/24 (0%)		1/22 (4.5%)
Gastrointestinal disorders
Abdominal Pain	1/24 (4.2%)		2/22 (9.1%)
Acute Cholycystitis	1/24 (4.2%)		0/22 (0%)
Acute Small Bowel Obstruction	1/24 (4.2%)		1/22 (4.5%)
Diarrhea	1/24 (4.2%)		0/22 (0%)
Enterocutaneous Fistula	0/24 (0%)		1/22 (4.5%)
Ischemic Colitis	0/24 (0%)		1/22 (4.5%)
Upper GI Hemorrhage	0/24 (0%)		1/22 (4.5%)
Vomiting	0/24 (0%)		1/22 (4.5%)
General disorders
Dehydration	1/24 (4.2%)		1/22 (4.5%)
Fatigue	0/24 (0%)		1/22 (4.5%)
Fever	2/24 (8.3%)		0/22 (0%)
Lethargy	0/24 (0%)		1/22 (4.5%)
Nausea	4/24 (16.7%)		1/22 (4.5%)
Oversedation	0/24 (0%)		1/22 (4.5%)
Pain	1/24 (4.2%)		0/22 (0%)
Subarachnoid Hemorrhage	1/24 (4.2%)		0/22 (0%)
Systemic Inflammatory Response Syndrome	1/24 (4.2%)		0/22 (0%)
Hepatobiliary disorders
Biliary Obstruction	1/24 (4.2%)		0/22 (0%)
Biliary Strictures	1/24 (4.2%)		0/22 (0%)
Biliary Tract Infection	1/24 (4.2%)		0/22 (0%)
Liver Abscess	1/24 (4.2%)		1/22 (4.5%)
Liver Failure	0/24 (0%)		1/22 (4.5%)
Subcapsular Liver Abscess	1/24 (4.2%)		0/22 (0%)
Infections and infestations
ESBL E Coli Bacteremia	1/24 (4.2%)		0/22 (0%)
ESBL E Coli Urinary Tract Infection	1/24 (4.2%)		0/22 (0%)
Neutropenic Sepsis	2/24 (8.3%)		0/22 (0%)
Pneumonia	1/24 (4.2%)		1/22 (4.5%)
Sepsis	2/24 (8.3%)		2/22 (9.1%)
Wound Infection	0/24 (0%)		1/22 (4.5%)
Investigations
Hypercalcemia	0/24 (0%)		1/22 (4.5%)
Hypoglycemia	1/24 (4.2%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Pelvic Fracture	0/24 (0%)		2/22 (9.1%)
Psychiatric disorders
Altered Mental Status	0/24 (0%)		1/22 (4.5%)
Renal and urinary disorders
Acute Kidney Injury	0/24 (0%)		1/22 (4.5%)
Acute Renal Failure	1/24 (4.2%)		1/22 (4.5%)
Acute Renal Insufficiency	1/24 (4.2%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/24 (0%)		1/22 (4.5%)
Respiratory Failure	0/24 (0%)		1/22 (4.5%)
Vascular disorders
Stroke	1/24 (4.2%)		1/22 (4.5%)
TIA	1/24 (4.2%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo		Randomization to Gem-Cis or Gem-Carbo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/24 (100%)		19/22 (86.4%)
Blood and lymphatic system disorders
Anemia	12/24 (50%)		9/22 (40.9%)
Bruising	2/24 (8.3%)		2/22 (9.1%)
Coagulopathy	0/24 (0%)		1/22 (4.5%)
Thrombosis	3/24 (12.5%)		2/22 (9.1%)
Epistaxis	2/24 (8.3%)		2/22 (9.1%)
Pancytopenia	2/24 (8.3%)		1/22 (4.5%)
Cardiac disorders
Ischemic Cardiomyopathy	1/24 (4.2%)		0/22 (0%)
Pericardial Effusion	1/24 (4.2%)		0/22 (0%)
Tachycardia	4/24 (16.7%)		1/22 (4.5%)
Ear and labyrinth disorders
Otitis Media	0/24 (0%)		2/22 (9.1%)
Gastrointestinal disorders
Abdominal Distension	3/24 (12.5%)		2/22 (9.1%)
Abdominal Pain	21/24 (87.5%)		5/22 (22.7%)
Constipation	17/24 (70.8%)		6/22 (27.3%)
Diarrhea	10/24 (41.7%)		7/22 (31.8%)
Dyspepsia	3/24 (12.5%)		2/22 (9.1%)
Esophageal Varices	0/24 (0%)		1/22 (4.5%)
Fecal Incontinence	1/24 (4.2%)		0/22 (0%)
Gastritis	2/24 (8.3%)		1/22 (4.5%)
GERD	0/24 (0%)		1/22 (4.5%)
Heartburn	2/24 (8.3%)		1/22 (4.5%)
Inguinal Hernia	1/24 (4.2%)		0/22 (0%)
Malabsorption	0/24 (0%)		1/22 (4.5%)
Nausea	20/24 (83.3%)		12/22 (54.5%)
Vomiting	15/24 (62.5%)		6/22 (27.3%)
weight Loss	6/24 (25%)		1/22 (4.5%)
General disorders
Agitation	1/24 (4.2%)		1/22 (4.5%)
Aguesia	3/24 (12.5%)		0/22 (0%)
Anorexia	3/24 (12.5%)		1/22 (4.5%)
Balance Problems	2/24 (8.3%)		0/22 (0%)
Edema	7/24 (29.2%)		6/22 (27.3%)
Bone Pain	2/24 (8.3%)		1/22 (4.5%)
Cachexia	0/24 (0%)		1/22 (4.5%)
Chills	3/24 (12.5%)		1/22 (4.5%)
Cold Sensitivity	1/24 (4.2%)		1/22 (4.5%)
Decreased Appetite	5/24 (20.8%)		3/22 (13.6%)
Dysgeusia	2/24 (8.3%)		7/22 (31.8%)
Dehydration	4/24 (16.7%)		4/22 (18.2%)
Diaphoresis	5/24 (20.8%)		0/22 (0%)
Dizziness	5/24 (20.8%)		3/22 (13.6%)
Early Satiety	2/24 (8.3%)		0/22 (0%)
Encephalopathy	0/24 (0%)		1/22 (4.5%)
Failure to Thrive	1/24 (4.2%)		0/22 (0%)
Fall	2/24 (8.3%)		0/22 (0%)
Fatigue	22/24 (91.7%)		6/22 (27.3%)
Fever	11/24 (45.8%)		3/22 (13.6%)
Gait Disturbance	1/24 (4.2%)		1/22 (4.5%)
Headache	4/24 (16.7%)		5/22 (22.7%)
Hematemesis	0/24 (0%)		1/22 (4.5%)
Insomnia	6/24 (25%)		1/22 (4.5%)
Jaundice	1/24 (4.2%)		0/22 (0%)
Malaise	1/24 (4.2%)		2/22 (9.1%)
Malnutrition	2/24 (8.3%)		2/22 (9.1%)
Mucositis	1/24 (4.2%)		3/22 (13.6%)
Parasthesia	1/24 (4.2%)		1/22 (4.5%)
Rash	3/24 (12.5%)		1/22 (4.5%)
Syncope	3/24 (12.5%)		0/22 (0%)
Weakness	3/24 (12.5%)		3/22 (13.6%)
Tremors	1/24 (4.2%)		1/22 (4.5%)
Hepatobiliary disorders
Ascites	2/24 (8.3%)		1/22 (4.5%)
Cholecystitis	1/24 (4.2%)		0/22 (0%)
Cholangitis	0/24 (0%)		1/22 (4.5%)
Immune system disorders
Gout	0/24 (0%)		1/22 (4.5%)
Alopecia	3/24 (12.5%)		2/22 (9.1%)
Infections and infestations
C Difficile	1/24 (4.2%)		0/22 (0%)
Cellulitis	2/24 (8.3%)		0/22 (0%)
Influenza	1/24 (4.2%)		0/22 (0%)
Upper Respiratory Infection	4/24 (16.7%)		0/22 (0%)
Investigations
Elevated Liver Enzymes	9/24 (37.5%)		3/22 (13.6%)
Hyperbilirubinemia	1/24 (4.2%)		0/22 (0%)
Hypercalcemia	1/24 (4.2%)		1/22 (4.5%)
Hyperglycemia	4/24 (16.7%)		2/22 (9.1%)
Hyperkalemia	2/24 (8.3%)		0/22 (0%)
Hypernatremia	1/24 (4.2%)		0/22 (0%)
Hypocalcemia	1/24 (4.2%)		1/22 (4.5%)
Hypokalemia	4/24 (16.7%)		3/22 (13.6%)
Hypomagnesemia	10/24 (41.7%)		6/22 (27.3%)
Hyponatremia	3/24 (12.5%)		0/22 (0%)
Leukopenia	6/24 (25%)		3/22 (13.6%)
Neutropenia	8/24 (33.3%)		8/22 (36.4%)
Thrombocytopenia	10/24 (41.7%)		7/22 (31.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/24 (12.5%)		1/22 (4.5%)
Back Pain	4/24 (16.7%)		4/22 (18.2%)
Body Aches	1/24 (4.2%)		1/22 (4.5%)
Myalgia	3/24 (12.5%)		1/22 (4.5%)
Nervous system disorders
Peripheral Neuropathy	7/24 (29.2%)		2/22 (9.1%)
Psychiatric disorders
Anxiety	3/24 (12.5%)		1/22 (4.5%)
Confusion	1/24 (4.2%)		2/22 (9.1%)
Delirium	2/24 (8.3%)		0/22 (0%)
Depression	1/24 (4.2%)		1/22 (4.5%)
Renal and urinary disorders
Dysuria	1/24 (4.2%)		2/22 (9.1%)
Urinary Tract Infection	4/24 (16.7%)		4/22 (18.2%)
Respiratory, thoracic and mediastinal disorders
Bronchitis	0/24 (0%)		1/22 (4.5%)
Cough	4/24 (16.7%)		2/22 (9.1%)
Dyspenea	6/24 (25%)		4/22 (18.2%)
Hemopthysis	1/24 (4.2%)		0/22 (0%)
Pleural Effusion	2/24 (8.3%)		0/22 (0%)
Skin and subcutaneous tissue disorders
Decubitus Ulcer	0/24 (0%)		1/22 (4.5%)
Dermatitis	1/24 (4.2%)		1/22 (4.5%)
Vascular disorders
Hypertension	12/24 (50%)		1/22 (4.5%)
Hypotension	2/24 (8.3%)		2/22 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.