SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma

• Sponsor: Sirtex Medical (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00503867
• Collaborator: (none)
• Enrollment: 10
• Locations: 4
• Arm: 1
• Actual Duration (Months): 31.7
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main purpose of this study is to determine the safety and toxicity of treatment with SIR-Spheres® in patients with unresectable primary liver cancer or hepatocellular carcinoma (HCC). Other purposes of this study include assessment of the effect of treatment on overall survival, the length of time it takes for the disease to worsen, if and how the treatment affects the patient's quality of life, and if and how the cancer responds to the treatment.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular; Hepatoma	Device: SIR-Spheres microspheres	N/A

Detailed Description

This study is a multi-institutional, non-randomized pilot study that aims to assess the safety and toxicity of hepatic arterial radioembolization using SIR-Spheres yttrium-90 microspheres (SIR-Spheres microspheres) in the treatment of patients with unresectable primary hepatocellular carcinoma (HCC). The study aims to recruit 40 patients over a period of 24 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Yttrium-90 Microspheres (SIR-Spheres®) Therapy for the Treatment of Unresectable Hepatocellular Carcinoma
• Actual Study Start Date: Jul 18, 2007
• Actual Primary Completion Date: Mar 9, 2010
• Actual Study Completion Date: Mar 9, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SIR-Spheres microspheres SIR-Spheres microspheres	Device: SIR-Spheres microspheres; SIR-Spheres Yttrium-90 microspheres

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events Grade 3 or Higher [From date of enrollment until the date of death from any cause assessed up 24 weeks.]

   Using the National Cancer Institute Common Terminology Criteria (NCI-CTC) version 3.0 as recorded in the case report form.

Secondary Outcome Measures

1. Time to Disease Progression [From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.]

   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.

2. Tumor Response Rate [From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.]

   Tumour response rates estimated by the proportion of patients with a best response of CR, PR or SD by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) with corresponding exact 90% confidence limits being reported. Per RECIST v1.0 for target lesions and assessed by CT or 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.

3. Change From Baseline in Health-related Quality of Life [52 weeks]

4. Overall Survival [From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.]

   Overall Survival is defined as the time interval between the date of enrollment and the date of death from any cause.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• must have a confirmed diagnosis of HCC.

• at least 18 years of age.

• must have a confirmed diagnosis of HCC either by histological confirmation or, in a subject who exhibits a vascular liver mass in the presence of radiographically apparent cirrhosis, an alpha-fetoprotein (AFP) level greater than 500 International Units/milliliter (UI/ml).

• must present HCC that is not amenable to surgical resection or immediate liver transplantation, or that is not optimally treatable with local ablative techniques such as radio-frequency ablation due to its size, extent or presence of cirrhosis.

• must present measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as greater than or equal to 10 mm with spiral CT scan or greater than or equal to 20 mm using conventional techniques (CT, MRI).

• must present with a whole-liver tumor burden of greater than or equal to 15% and less than or equal to 70%

• must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.

• must have normal organ and marrow function

Exclusion criteria:

Includes both the listed contraindications to SIR-Spheres® and the exclusion criteria specific to the setting of this investigational study:

• hepatic artery directed therapy within the previous 6 months.

• chemotherapy within the previous 4 weeks

• have not recovered from adverse events due to agents administered previously

• Prior external hepatic radiation therapy for HCC, more than two prior systemic chemotherapy regimes for HCC or any other concomitant therapy for HCC

• Currently receiving any other investigational agents for the treatment of their cancer.

• Any extra-hepatic metastases other than metastatic disease found in the lung, bone and/or abdominal lymph nodes that are not otherwise life limiting.

• Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least five years.

• Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.

• Any of the following contraindications to angiography and selective visceral catheterization:

• Bleeding diathesis

• Severe peripheral vascular disease

• Portal hypertension with hepatofugal flow

• Female subjects who are pregnant or currently breastfeeding.

• Refusal or inability to use effective means of contraception in men or women of childbearing potential.

• Current enrollment in any other investigational drug or device study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University - Kimmel Cancer Center	Philadelphia	Pennsylvania	United States	19107
2	UPMC Liver Cancer Center	Pittsburgh	Pennsylvania	United States	15213
3	The Liver Institute at Methodist Dallas	Dallas	Texas	United States	75203
4	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Sirtex Medical

Investigators

• Principal Investigator: Ravi Murthy, MD, M.D. Anderson Cancer Center
• Principal Investigator: T. Clark Gamblin, MD, UPMC Liver Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sirtex Medical
• ClinicalTrials.gov Identifier: NCT00503867
• Other Study ID Numbers: STX 0106
• First Posted: Jul 19, 2007
• Last Update Posted: Dec 10, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sirtex Medical: unresectable hepatocellular carcinoma; HCC; SIR-Spheres; Y-90 Microspheres; brachytherapy; Selective Internal Radiation Therapy (SIRT); liver cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

Participant Flow

Recruitment Details	Three medical centers in the US enrolled 10 patients from July 18, 2007 to March 9, 2010.

Arm/Group Title	SIR-Spheres Microspheres
Arm/Group Description	Radioembolization treatment with SIR-Spheres microspheres is administered within 28 days of enrollment into the study.
Period Title: Overall Study
STARTED	10
COMPLETED	8
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Hepatic Arterial Radioembolization SIR-Spheres Microspheres
Arm/Group Description	SIR-Spheres microspheres SIR-Spheres microspheres: SIR-Spheres Yttrium-90 microspheres
Overall Participants	10
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	68.0
Sex: Female, Male (Count of Participants)
Female	4 40%
Male	6 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%
Not Hispanic or Latino	9 90%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 20%
White	8 80%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%
ECOG performance status (Count of Participants)
0 (full activity)	8 80%
1 (ambulatory restricted)	2 20%
Previous chemotherapy (Count of Participants)
Yes	1 10%
No	9 90%
Previous radiotherapy (Count of Participants)
Yes	1 10%
No	9 90%
Disease characteristics (Count of Participants)
Okuda Stage 1	10 100%
CLIP score Class 1	4 40%
CLIP score Class 2	2 20%
CLIP score Class Unknown	4 40%
Cirrhosis (Yes)	8 80%
Cirrhosis (No)	2 20%
TNM Classification of Primary Tumor, T2	2 20%
TNM Classification of Primary Tumor, T3	6 60%
TNM Classification of Primary Tumor, T4	2 20%
TNM Classification of regional lymph nodes (No)	10 100%
Hepatitis B (Yes)	1 10%
Hepatitis B (No)	9 90%
Hepatitis C (Yes)	3 30%
Hepatitis C (No)	7 70%
Metabolic Liver Disease (No)	10 100%
History of alcohol abuse (Yes)	3 30%
History of alcohol abuse (No)	7 70%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events Grade 3 or Higher
Description	Using the National Cancer Institute Common Terminology Criteria (NCI-CTC) version 3.0 as recorded in the case report form.
Time Frame	From date of enrollment until the date of death from any cause assessed up 24 weeks.

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received initial SIRT treatment.

Arm/Group Title	SIR-Spheres Microspheres
Arm/Group Description	Radioembolization treatment with SIR-Spheres microspheres is administered within 28 days of enrollment into the study.
Measure Participants	10
Count of Participants [Participants]	3 30%

2. Secondary Outcome

Title	Time to Disease Progression
Description	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	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed as no data was collected prior to termination of the study.

Arm/Group Title	SIR-Spheres Microspheres
Arm/Group Description	Radioembolization treatment with SIR-Spheres microspheres is administered within 28 days of enrollment into the study.
Measure Participants	0

3. Secondary Outcome

Title	Tumor Response Rate
Description	Tumour response rates estimated by the proportion of patients with a best response of CR, PR or SD by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) with corresponding exact 90% confidence limits being reported. Per RECIST v1.0 for target lesions and assessed by CT or 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	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed as no data was collected prior to termination of the study.

Arm/Group Title	SIR-Spheres Microspheres
Arm/Group Description	Radioembolization treatment with SIR-Spheres microspheres is administered within 28 days of enrollment into the study.
Measure Participants	0

4. Secondary Outcome

Title	Change From Baseline in Health-related Quality of Life
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed as no data was collected prior to termination of the study.

Arm/Group Title	SIR-Spheres Microspheres
Arm/Group Description	Radioembolization treatment with SIR-Spheres microspheres is administered within 28 days of enrollment into the study.
Measure Participants	0

5. Secondary Outcome

Title	Overall Survival
Description	Overall Survival is defined as the time interval between the date of enrollment and the date of death from any cause.
Time Frame	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.

Outcome Measure Data

Analysis Population Description

This outcome measure was not assessed as no data was collected prior to termination of the study.

Arm/Group Title	SIR-Spheres Microspheres
Arm/Group Description	Radioembolization treatment with SIR-Spheres microspheres is administered within 28 days of enrollment into the study.
Measure Participants	0

Adverse Events

Time Frame	From consent until 24 weeks post last dose of protocol chemotherapy.
Arm/Group Title	SIR-Spheres Microspheres
Arm/Group Description	Radioembolization treatment with SIR-Spheres microspheres is administered within 28 days of enrollment into the study.
All Cause Mortality
	SIR-Spheres Microspheres
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SIR-Spheres Microspheres
	Affected / at Risk (%)	# Events
Total	3/10 (30%)
Cardiac disorders
Dyspnoea	1/10 (10%)	1
Gastrointestinal disorders
Abdominal Distention	1/10 (10%)	1
General disorders
Asthenia	1/10 (10%)	1
Chest Pain	1/10 (10%)	1
Hepatobiliary disorders
Hyperbilirubinemia	1/10 (10%)	1
Investigations
International Normalised Radio Increased	1/10 (10%)	1
Metabolism and nutrition disorders
Hypoglycaemia	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	SIR-Spheres Microspheres
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

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.