Phase II SBRT & Chemo for Unresectable Cholangiocarcinoma Followed by Liver Transplantation

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01151761
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 18
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine progression-free survival at 12 months for stereotactic body radiotherapy (SBRT) and chemotherapy for unresectable hilar cholangiocarcinoma (CCA).

Condition or Disease	Intervention/Treatment	Phase
Cholangiocarcinoma; Hepatobiliary Neoplasm; Liver Cancer; Bile Duct Cancer; Cancer of Gallbladder	Procedure: Stereotactic Body Radiotherapy; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Capecitabine; Drug: 5FU; Procedure: Liver transplantation	Phase 2

Detailed Description

Investigators hope to learn more about neoadjuvant SBRT and chemotherapy for unresectable CCA, and if SBRT followed by chemotherapy can lead to successful liver transplantation. This knowledge is important for this patient group as this disease is a highly lethal malignancy that often presents as unresectable, however surgery or transplantation are the only curative options.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Stereotactic Body Radiotherapy (SBRT) and Chemotherapy for Unresectable Cholangiocarcinoma Followed by Liver Transplantation
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: SBRT, Chemo and Liver Transplantation The patients received Stereotactic Body Radiotherapy and Chemotherapy followed by a liver transplantation. The chemo could be any combination of the following: Gemcitabine, Cisplatin, Carboplatin, Capecitabine and 5FU

Procedure: Stereotactic Body Radiotherapy; Standard of care; Other Names: External photon radiation ; Drug: Gemcitabine; 100 mg/m2, IV; Other Names: Gemzar ; Drug: Cisplatin; 25 mg/m2, IV; Other Names: Platinol Platinol-AQ ; Drug: Carboplatin; AUC 2, based on Calvert formula, IV; Other Names: Paraplatin Paraplatin-AQ ; Drug: Capecitabine; 1000 mg/m2, PO; Other Names: Xeloda ; Drug: 5FU; 200 mg/m2; Other Names: Fluorouracil Adrucil Carac Efudix Efudex Fluoroplex ; Procedure: Liver transplantation

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival at 12 Months [12 months]

   Progression free survival is defined to be the time to progression of disease or death.

Secondary Outcome Measures

1. Pathologic Complete Response Rate [12 months]

   Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen.

2. Serum CA 19-9 Levels [12 months]

   Initial level of Cancer antigen 19-9

3. Overall Survival at 12 Months [12 months]

   the estimated probability for the percentage of participants with overall survival at 12 months.

4. Liver Transplant Rate [12 months]

   The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm

5. Freedom From Local Progression at 12 Months [12 months]

   the proportion of patients who experienced a local recurrence at 12 months with death as a competing risk

6. Liver Transplant Conversion Rate [12 months]

   The ability to successfully perform liver transplant among patients who initially have tumor >3 cm

7. Median Time to Overall Survival [18 months]

   The time to overall survival is defined as the time to death from any cause. The median was determined via Kaplan Meier methodology.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of cholangiocarcinoma by any of the below:

• Positive transcatheter biopsy or brush cytology

• CA 19-9 ≥ 100mg/mL with a malignant-appearing stricture on cholangiography

• Biliary ploidy by fluorescent in situ hybridization with a malignant stricture on cholangiography

• Liver tumors not to exceed 8 cm in greatest axial dimension (800 cc of uninvolved liver)

• Unresectable tumor above cystic duct

• Hepatic lesion in patients for whom surgical resection is not possible or would not result in an opportunity for cure by any of the below:

• Bilateral segmental ductal extension

• Encasement of the main portal vein

• Unilateral segmental ductal extension with contralateral vascular encasement

• Unilateral atrophy with either contralateral segmental ductal or vascular (hepatic artery, portal vein) involvement

• Ascites is allowed if the Model for End-Stage Liver Disease (MELD) score is <15[1]

• Age > 18 years old

• Eastern Clinical Oncology Group performance status 0, 1 or 2 (Appendix 1)

• Lab values within 2 wks prior to randomization:

• See STUDY SCHEMA for specific blood count inclusion criteria: ANC ≥ 500 x 109/L (≥ 1500/mm3), Platelets ≥ 5 x 109/L (≥ 50,000/mm3), Hgb ≥ 9g/dL

• Adequate liver function: Total bilirubin ≤1.5 x upper limit of normal (ULN); ALT and/or AST & alkaline phosphatase ≤ 5 x ULN.

• Adequate biliary drainage, with no evidence of active uncontrolled infection (patients on antibiotics are eligible).

• See STUDY SCHEMA for specific renal function inclusion criteria: Adequate renal function with a calculated GFR ≥ 40 ml/min. If the calculated GFR is below 40 ml/min a 24 hour urine creatinine clearance can be used.

• Albumin > 2.5 mg/dL

• INR ≤ 1.5

• Life expectancy > 6 months

• Capable of giving written informed consent

Exclusion Criteria:

• Prior radiotherapy to the upper abdomen

• Contraindication to receiving radiotherapy

• Prior chemotherapy

• Prior biliary resection or attempted resection

• Prior transperitoneal biopsy

• Large esophageal varices without band ligation

• Active GI bleed or within 2 weeks of study enrollment

• Ascites refractory to medical therapy or shunting

• Active/unresolved biliary tract obstruction

• Presence of multifocal, lymphatic, or extrahepatic metastases

• Participation in another concurrent treatment protocol

• If history of other primary cancer, subject eligible only if she or he has:

• Curatively resected non-melanomatous skin cancer

• Curatively treated cervical carcinoma in situ

• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years

• Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial

• Any psychiatric or other disorder (eg brain metastases) likely to impact on informed consent

• Pregnancy or breast-feeding

• While not excluded, patients with significant impaired hearing must be made aware of potential ototoxicity and may choose not to be included. If included, baseline audiograms are recommended and, in those given cisplatin, should be followed by repeat audiograms prior to cycle 2.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Daniel T Chang, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daniel T. Chang, Assistant Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT01151761
• Other Study ID Numbers: HEP0032; HEP0032
• First Posted: Jun 28, 2010
• Last Update Posted: Jul 29, 2016
• Last Verified: Jun 1, 2016

• Additional relevant MeSH terms: Cholangiocarcinoma; Bile Duct Neoplasms; Gallbladder Neoplasms; Gemcitabine; Cisplatin; Carboplatin; Fluorouracil; Capecitabine

Study Results

Participant Flow

Recruitment Details	The location is the Stanford Cancer Center. The study was open to accrual 1/18/2011. The study closed on 9/28/2012.

Arm/Group Title	SBRT, Chemotherapy and Liver Transplantation
Arm/Group Description	The patients received Stereotactic Body Radiotherapy and Chemotherapy followed by a liver transplantation. The chemo could be any combination of the following: Gemcitabine, Cisplatin, Carboplatin, Capecitabine and 5FU
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	SBRT, Chemotherapy and Liver Transplantation
Arm/Group Description	The patients received Stereotactic Body Radiotherapy and Chemotherapy followed by a liver transplantation. The chemo could be any combination of the following: Gemcitabine, Cisplatin, Carboplatin, Capecitabine and 5FU
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 50%
>=65 years	1 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.5 (9.19)
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival at 12 Months
Description	Progression free survival is defined to be the time to progression of disease or death.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT and Chemo
Arm/Group Description	The patients in this arm receive SBRT and chemo in the hope of surviving long enough to have a liver transplantation
Measure Participants	2
Number [participants]	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SBRT and Chemo
	Comments	The median Progression Free Survival (PFS) time as calculated using Kaplan Meier methodology. For PFS both death and progression are counted as events.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	months
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 95%; 7 to 10
	Parameter Dispersion	Type: Value:
	Estimation Comments	There were only two patients in the study. Both died without having any local failure. One patient died at 10 months, the other at 7 months. The range for the 95%CI is both the full range and the 95%CI.

2. Secondary Outcome

Title	Pathologic Complete Response Rate
Description	Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT and Chemo
Arm/Group Description	The patients in this arm receive SBRT and chemo in the hope of surviving long enough to have a liver transplantation
Measure Participants	2
Number [participants]	0 0%

3. Secondary Outcome

Title	Serum CA 19-9 Levels
Description	Initial level of Cancer antigen 19-9
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT and Chemo
Arm/Group Description	The patients in this arm receive SBRT and chemo in the hope of surviving long enough to have a liver transplantation
Measure Participants	2
Mean (Full Range) [U/ml]	3329.1

4. Secondary Outcome

Title	Overall Survival at 12 Months
Description	the estimated probability for the percentage of participants with overall survival at 12 months.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

There were only two patients analyzed. Please take that under advisement when looking at the results.

Arm/Group Title	SBRT and Chemo
Arm/Group Description	The patients in this arm receive SBRT and chemo in the hope of surviving long enough to have a liver transplantation
Measure Participants	2
Number [probability]	0

5. Secondary Outcome

Title	Liver Transplant Rate
Description	The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT and Chemo
Arm/Group Description	The patients in this arm receive SBRT and chemo in the hope of surviving long enough to have a liver transplantation
Measure Participants	2
Number [participants]	0 0%

6. Secondary Outcome

Title	Freedom From Local Progression at 12 Months
Description	the proportion of patients who experienced a local recurrence at 12 months with death as a competing risk
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Neither of the two patients that participated in the study had a local recurrence prior to dying.

Arm/Group Title	SBRT and Chemo
Arm/Group Description	The patients in this arm receive SBRT and chemo in the hope of surviving long enough to have a liver transplantation
Measure Participants	2
Number [percentage of patients]	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SBRT and Chemo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of participants
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	None of the two patients who participated had a local recurrence before they died.

7. Secondary Outcome

Title	Liver Transplant Conversion Rate
Description	The ability to successfully perform liver transplant among patients who initially have tumor >3 cm
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT and Chemo
Arm/Group Description	The patients in this arm receive SBRT and chemo in the hope of surviving long enough to have a liver transplantation
Measure Participants	2
Number [participants]	0 0%

8. Secondary Outcome

Title	Median Time to Overall Survival
Description	The time to overall survival is defined as the time to death from any cause. The median was determined via Kaplan Meier methodology.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT and Chemo
Arm/Group Description	The patients in this arm receive SBRT and chemo in the hope of surviving long enough to have a liver transplantation
Measure Participants	2
Median (95% Confidence Interval) [months]	8.5

Adverse Events

Time Frame	The entire period of the study, 2 years
Arm/Group Title	SBRT, Chemotherapy and Liver Transplantation
Arm/Group Description	The patients received Stereotactic Body Radiotherapy and Chemotherapy followed by a liver transplantation. The chemo could be any combination of the following: Gemcitabine, Cisplatin, Carboplatin, Capecitabine and 5FU
All Cause Mortality
	SBRT, Chemotherapy and Liver Transplantation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SBRT, Chemotherapy and Liver Transplantation
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Hepatobiliary disorders
Hepatic failure (encephalopathy)	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	SBRT, Chemotherapy and Liver Transplantation
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

Early termination due to low accrual.

More Information

Certain Agreements

All Principal Investigators ARE 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.