A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC)

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02821754
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arms: 4
• Anticipated Duration (Months): 77.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

BACKGROUND:

• Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. The term ablative therapies applies to trans-arterial catheter chemoembolization (TACE), radiofrequency ablation (RFA) and cryoablation (CA).

• The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE, CA and RFA in patients with advanced hepatocellular carcinoma (HCC) and biliary tract carcinomas (BTC). We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy.

• Based on the concept of programmed death-ligand 1 (PDL1)-mediated adaptive resistance and the emerging role of programmed cell death protein 1 (PD1) therapy in HCC, we would like to evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in HCC and BTC.

Objectives:

• To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (either alone or with cryoablation, TACE or RFA) and in patients with advanced biliary tract carcinoma (BTC) (either alone or with cryoablation or RFA).

ELIGIBILITY:

• Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma).

• Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply.

• Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.

DESIGN:

We will evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in cohorts A (HCC; N=40) and B (BTC; N=30). The first N=10 patients in both cohorts will receive tremelimumab and durvalumab only (i.e. No interventional radiologic procedures).

• A: Advanced HCC, BCLC# Stage B/C

• N= 1st 10 pts: No ablative procedure Cryoablation/RFA/TACE##

• Tremelimumab 75mg flat dose every (q)28 days for 4 doses; Durvalumab 1500mg flat dose q28 days until end of study (EOS)###

• 40 total: 10 trem+ dur alone; 10 trem+ dur + TACE; 10 trem + dur + RFA; 10 trem + dur + cryo

• B: Intra/extra-hepatic cholangiocarcinoma

• N= 1st 10 patients (pts): No ablative procedure; RFA/ cryoablation

• Tremelimumab 75mg flat dose q28 days for 4 doses; Durvalumab 1500mg flat dose q28 days until EOS###

• 30 total: 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem

• BCLC = Barcelona clinic liver cancer staging system

• For BCLC stage B patients TACE may be repeated as per standard of care

• EOS = End of study treatment or meeting any of the off-treatment or off study criteria.

Condition or Disease	Intervention/Treatment	Phase
Biliary Tract Neoplasms; Liver Cancer; Hepatocellular Carcinoma; Cholangiocarcinoma; Bile Duct Cancer	Drug: Durvalumab; Drug: Tremelimumab; Procedure: Trans-arterial Catheter Chemoembolization (TACE); Procedure: Radiofrequency Ablation (RFA); Procedure: Cryoablation	Phase 2

Detailed Description

BACKGROUND:

• Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. The term ablative therapies applies to trans-arterial catheter chemoembolization (TACE), radiofrequency ablation (RFA) and cryoablation (CA).

• The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE, CA and RFA in patients with advanced hepatocellular carcinoma (HCC) and biliary tract carcinomas (BTC). We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-CTLA4 therapy.

• Based on the concept of PDL1-mediated adaptive resistance and the emerging role of PD1 therapy in HCC, we would like to evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in HCC and BTC.

Objectives:

• To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (either alone or with cryoablation, TACE or RFA) and in patients with advanced biliary tract carcinoma (BTC) (either alone or with cryoablation or RFA).

ELIGIBILITY:

• Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma).

• Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply.

• Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.

DESIGN:

We will evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in cohorts A1 (HCC; Barcelona clinic liver cancer staging system (BCLC) stage C; N=10), A2 (HCC; BCLC stages B/C; N=30) and B (BTC; N=30). The patients in cohort A1 and first 10 patients in cohort B will receive tremelimumab and durvalumab only (i.e. no interventional radiologic procedures).

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC)
• Actual Study Start Date: Jul 5, 2016
• Actual Primary Completion Date: Feb 17, 2021
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1/A1-Durvalumab + Tremelimumab Durvalumab + Tremelimumab	Drug: Durvalumab; Flat dose of 1500 mg every 4 weeks.; Other Names: Imfinzi ; Drug: Tremelimumab; Flat dose of 75 mg every 4 weeks for up to 4 doses.; Other Names: Ticilimumab
Experimental: 2/A2 - Durvalumab + Tremelimumab + Trans-arterial Catheter Chemoembolization (TACE) Durvalumab + Tremelimumab + TACE	Drug: Durvalumab; Flat dose of 1500 mg every 4 weeks.; Other Names: Imfinzi ; Drug: Tremelimumab; Flat dose of 75 mg every 4 weeks for up to 4 doses.; Other Names: Ticilimumab ; Procedure: Trans-arterial Catheter Chemoembolization (TACE); TACE will be performed on Day 36 (+/-96hrs).; Other Names: TACE
Experimental: 3/A3 - Durvalumab + Tremelimumab+ Radiofrequency Ablation (RFA) Durvalumab + Tremelimumab+ RFA	Drug: Durvalumab; Flat dose of 1500 mg every 4 weeks.; Other Names: Imfinzi ; Drug: Tremelimumab; Flat dose of 75 mg every 4 weeks for up to 4 doses.; Other Names: Ticilimumab ; Procedure: Radiofrequency Ablation (RFA); RFA will be performed on Day 36 (+/-96hrs).; Other Names: RFA
Experimental: 4/A4 - Durvalumab + Tremelimumab+ Cryoablation Durvalumab + Tremelimumab+ Cryoablation	Drug: Durvalumab; Flat dose of 1500 mg every 4 weeks.; Other Names: Imfinzi ; Drug: Tremelimumab; Flat dose of 75 mg every 4 weeks for up to 4 doses.; Other Names: Ticilimumab ; Procedure: Cryoablation; Cryoablation will be performed on Day 36 (+/-96hrs).; Other Names: Cryosurgery

Outcome Measures

Primary Outcome Measures

1. 6 Month Progression Free Survival (PFS) [At 6 months]

   PFS is the median amount of time subject survives without disease progression 6 months after treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

1. Number of Grades 1-5 Adverse Events Related to Tremelimumab and Durvalumab [60 days after last treatment, an average of 44.89 months]

   Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4.0. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.

Other Outcome Measures

1. Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) [Date treatment consent signed to date off study, approximately 62 months and 3 days for the RFA/TACE group, and 27 months and 24 days for the RFA/CA group.]

   Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Eligibility Criteria

Criteria

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

• INCLUSION CRITERIA:

1. Patients must have histopathological confirmation of hepatocellular carcinoma (HCC) or biliary tract carcinoma (BTC) by the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this study OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma). Fibrolamellar variant is also allowed. The term BTC includes intra or extrahepatic cholangiocarcinoma, gallbladder cancer or ampullary cancer.

2. Patients must have disease that is not amenable to potentially curative resection, transplantation or ablation. HCC patients must have progressed on, been intolerant to, or refused prior sorafenib therapy. Patients with BTC must have received, been intolerant of or refused at least one line of chemotherapy.

3. Patients must have multiple tumor lesions (at least 2): one for the ablation procedure and another for evaluation located outside the proposal ablation zone.

4. Disease must be technically amenable to transhepatic arterial chemoembolization (TACE) (HCC patients only), radiofrequency ablation (RFA), or cryoablation. Each case will be discussed at gastrointestinal (GI) tumor board with interventional radiology. Patients must have evaluable disease.

5. If liver cirrhosis is present, patient must have a Child-Pugh A/B7 classification

6. Age 18 years or older

7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

8. Patients must have normal organ and marrow function as defined below:

• leukocytes greater than or equal to 3,000/mcL

• absolute neutrophil count greater than or equal to 1,000/mcL

• platelets greater than or equal to 60,000/mcL

• total bilirubin If cirrhosis present: Part of Child Pugh requirement; If no cirrhosis: bilirubin should be less than or equal to 2 x upper limit of normal (ULN)

• serum albumin If cirrhosis present: Part of Child Pugh requirement; If no cirrhosis: albumin should be less than or equal to 2.5g/dl

• patients are eligible with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) up to 5 x ULN.

• creatinine < 1.5x institution upper limit of normal OR creatinine clearance greater than or equal to 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

1. Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.

2. Patients must not have other invasive malignancies within the past 5 years (with the exception of non-melanoma skin cancers, non-invasive bladder cancer or localized prostate cancer for whom systemic therapy is not required).

3. Patient must be able to understand and willing to sign a written informed consent document.

4. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

• Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

• Women greater than or equal to 50 years of age would be considered post-menopausal if they have been

amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

1. Body weight greater than 30kg

EXCLUSION CRITERIA:

1. Patients who have had standard of care chemotherapy, large field radiotherapy, or major surgery must wait 2 weeks prior to entering the study. For recent experimental therapies a 28 day period of time must elapse before treatment.

2. Patients who have undergone prior liver transplantation are ineligible.

3. Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations that would limit compliance with study requirements.

5. History of chronic autoimmune disease (e.g., Addison's disease, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, rheumatoid arthritis, hypophysitis, etc.) with symptomatic disease within the 3 years before randomization. Note: Active vitiligo or a history of vitiligo will not be a basis for exclusion.

6. Dementia or significantly altered mental status that would prohibit the understanding or rendering of Information and Consent and compliance with the requirements of the protocol.

7. Diverticulitis either active or history of within the past 2 years. Note that diverticulosis is permitted.

8. Active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegener's granulomatosis. Currently receiving immunosuppressive doses of steroids or other immunosuppressive medications (inhaled and topical steroids are permitted)

9. History of sarcoidosis syndrome

10. Patients should not be vaccinated with live attenuated vaccines within 30 days of starting durvalumab or tremelimumab treatment.

11. Has a known history of Human Immunodeficiency Virus (HIV). HIV-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and tremelimumab. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that tremelimumab may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events.

12. History of hypersensitivity reaction to human or mouse antibody products.

13. Pregnancy and breast feeding are exclusion factors. The effects of tremelimumab on the developing human fetus are unknown. Enrolled patients must agree to use adequate contraception prior to study entry, the duration of study participation and 6 months after the end of the treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

14. Patients with unhealed surgical wounds for more than 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Tim F Greten, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 28, 2021
• Informed Consent Form: Cohort: Affected Patient Consent - May 18, 2021
• Informed Consent Form: Drug Only Consent - Jun 26, 2017
• Informed Consent Form: Drug and Ablative Therapy Consent - Jun 26, 2017

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.
• Duffy AG, Greten TF. Immunological off-target effects of standard treatments in gastrointestinal cancers. Ann Oncol. 2014 Jan;25(1):24-32. doi: 10.1093/annonc/mdt349. Epub 2013 Nov 7. Review.
• Sangro B, Gomez-Martin C, de la Mata M, Iñarrairaegui M, Garralda E, Barrera P, Riezu-Boj JI, Larrea E, Alfaro C, Sarobe P, Lasarte JJ, Pérez-Gracia JL, Melero I, Prieto J. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. J Hepatol. 2013 Jul;59(1):81-8. doi: 10.1016/j.jhep.2013.02.022. Epub 2013 Mar 4.

• Responsible Party: Tim Greten, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02821754
• Other Study ID Numbers: 160135; 16-C-0135
• First Posted: Jul 4, 2016
• Last Update Posted: Mar 24, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tim Greten, M.D., Principal Investigator, National Cancer Institute (NCI): PDL1-Mediated Adaptive Resistance; Monoclonal Antibody; CTLA-4; Ablative Therapy; Combination of Tremelimumab and Durvalumab
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Cholangiocarcinoma; Bile Duct Neoplasms; Biliary Tract Neoplasms; Durvalumab; Tremelimumab

Study Results

Participant Flow

Pre-assignment Detail	Two participants were enrolled but not treated. With the exception of baseline data, no other data were collected for these participants.

Arm/Group Title	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)	Radiofrequency Ablation/Cryoablation (RFA/CA)	Enrolled But Not Treated
Arm/Group Description	RFA/TACE Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation	Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation	Enrolled but not treated.
Period Title: Overall Study
STARTED	36	16	2
COMPLETED	20	4	0
NOT COMPLETED	16	12	2

Baseline Characteristics

Arm/Group Title	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)	Radiofrequency Ablation/Cryoablation (RFA/CA)	Enrolled But Not Treated	Total
Arm/Group Description	RFA/TACE Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation	Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation	Enrolled but not treated.	Total of all reporting groups
Overall Participants	36	16	2	54
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	17 47.2%	12 75%	1 50%	30 55.6%
>=65 years	19 52.8%	4 25%	1 50%	24 44.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.54 (12.57)	57.59 (14.24)	66.1 (3.25)	62.54 (13.13)
Sex: Female, Male (Count of Participants)
Female	9 25%	6 37.5%	1 50%	16 29.6%
Male	27 75%	10 62.5%	1 50%	38 70.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 11.1%	0 0%	0 0%	4 7.4%
Not Hispanic or Latino	32 88.9%	16 100%	2 100%	50 92.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.8%	0 0%	0 0%	1 1.9%
Asian	6 16.7%	0 0%	0 0%	6 11.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	12 33.3%	0 0%	0 0%	12 22.2%
White	15 41.7%	16 100%	2 100%	33 61.1%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 5.6%	0 0%	0 0%	2 3.7%
Region of Enrollment (participants) [Number]
United States	36 100%	16 100%	2 100%	54 100%

Outcome Measures

1. Primary Outcome

Title	6 Month Progression Free Survival (PFS)
Description	PFS is the median amount of time subject survives without disease progression 6 months after treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)	Radiofrequency Ablation/Cryoablation (RFA/CA)
Arm/Group Description	RFA/TACE Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation	Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation
Measure Participants	36	1
Median (Full Range) [Months]	2.8	NA

2. Secondary Outcome

Title	Number of Grades 1-5 Adverse Events Related to Tremelimumab and Durvalumab
Description	Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4.0. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.
Time Frame	60 days after last treatment, an average of 44.89 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)	Radiofrequency Ablation/Cryoablation (RFA/CA)
Arm/Group Description	RFA/TACE Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation	Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation
Measure Participants	36	16
Grade 1	355	233
Grade 2	125	133
Grade 3	62	50
Grade 4	6	3
Grade 5	0	2

3. Other Pre-specified Outcome

Title	Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Description	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame	Date treatment consent signed to date off study, approximately 62 months and 3 days for the RFA/TACE group, and 27 months and 24 days for the RFA/CA group.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)	Radiofrequency Ablation/Cryoablation (RFA/CA)
Arm/Group Description	RFA/TACE Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation	Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation
Measure Participants	36	16
Count of Participants [Participants]	36 100%	16 100%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 62 months and 3 days for the RFA/TACE group, and 27 months and 24 days for the RFA/CA group.
Arm/Group Title	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)		Radiofrequency Ablation/Cryoablation (RFA/CA)
Arm/Group Description	RFA/TACE Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation		Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study. 30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation
All Cause Mortality
	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)		Radiofrequency Ablation/Cryoablation (RFA/CA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/36 (72.2%)		15/16 (93.8%)
Serious Adverse Events
	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)		Radiofrequency Ablation/Cryoablation (RFA/CA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/36 (55.6%)		7/16 (43.8%)
Blood and lymphatic system disorders
Anemia	2/36 (5.6%)	2	1/16 (6.3%)	2
Cardiac disorders
Atrial fibrillation	2/36 (5.6%)	2	0/16 (0%)	0
Chest pain - cardiac	0/36 (0%)	0	1/16 (6.3%)	2
Supraventricular tachycardia	0/36 (0%)	0	1/16 (6.3%)	1
Gastrointestinal disorders
Abdominal pain	2/36 (5.6%)	2	2/16 (12.5%)	2
Ascites	2/36 (5.6%)	3	0/16 (0%)	0
Colitis	1/36 (2.8%)	1	1/16 (6.3%)	1
Diarrhea	1/36 (2.8%)	2	0/16 (0%)	0
Dry mouth	1/36 (2.8%)	1	0/16 (0%)	0
Gastritis	1/36 (2.8%)	1	0/16 (0%)	0
Ileal obstruction	1/36 (2.8%)	1	0/16 (0%)	0
Jejunal perforation	1/36 (2.8%)	1	0/16 (0%)	0
Mucositis oral	1/36 (2.8%)	1	0/16 (0%)	0
Nausea	1/36 (2.8%)	1	0/16 (0%)	0
Pancreatitis	0/36 (0%)	0	1/16 (6.3%)	2
General disorders
Edema limbs	1/36 (2.8%)	1	0/16 (0%)	0
Fever	1/36 (2.8%)	2	3/16 (18.8%)	3
Pain	3/36 (8.3%)	3	0/16 (0%)	0
Hepatobiliary disorders
Hepatic hemorrhage	1/36 (2.8%)	1	0/16 (0%)	0
Immune system disorders
Allergic reaction	0/36 (0%)	0	1/16 (6.3%)	1
Anaphylaxis	1/36 (2.8%)	1	0/16 (0%)	0
Immune system disorders - Other, Skin rash near anus	1/36 (2.8%)	1	0/16 (0%)	0
Infections and infestations
Infections and infestations - Other, Cellulitis - infection left upper extremity	1/36 (2.8%)	1	0/16 (0%)	0
Infections and infestations - Other, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)	2/36 (5.6%)	2	0/16 (0%)	0
Infections and infestations - Other, biliary stent infection	0/36 (0%)	0	1/16 (6.3%)	1
Lung infection	1/36 (2.8%)	1	0/16 (0%)	0
Sepsis	0/36 (0%)	0	2/16 (12.5%)	2
Investigations
Alanine aminotransferase increased	1/36 (2.8%)	3	1/16 (6.3%)	1
Alkaline phosphatase increased	0/36 (0%)	0	1/16 (6.3%)	1
Aspartate aminotransferase increased	1/36 (2.8%)	2	3/16 (18.8%)	3
Blood bilirubin increased	2/36 (5.6%)	2	2/16 (12.5%)	2
Platelet count decreased	1/36 (2.8%)	3	0/16 (0%)	0
Weight loss	1/36 (2.8%)	1	0/16 (0%)	0
Metabolism and nutrition disorders
Dehydration	2/36 (5.6%)	2	0/16 (0%)	0
Hyperglycemia	1/36 (2.8%)	1	0/16 (0%)	0
Hyperkalemia	2/36 (5.6%)	2	0/16 (0%)	0
Hyponatremia	1/36 (2.8%)	1	0/16 (0%)	0
Hypophosphatemia	1/36 (2.8%)	1	0/16 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/36 (2.8%)	1	0/16 (0%)	0
Back pain	2/36 (5.6%)	2	0/16 (0%)	0
Generalized muscle weakness	0/36 (0%)	0	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorder - Other, Myasthenia Gravis	1/36 (2.8%)	1	0/16 (0%)	0
Myalgia	1/36 (2.8%)	2	0/16 (0%)	0
Myositis	1/36 (2.8%)	1	0/16 (0%)	0
Non-cardiac chest pain	1/36 (2.8%)	1	0/16 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Death	3/36 (8.3%)	3	1/16 (6.3%)	1
Nervous system disorders
Depressed level of consciousness	1/36 (2.8%)	1	0/16 (0%)	0
Encephalopathy	2/36 (5.6%)	2	0/16 (0%)	0
Stroke	1/36 (2.8%)	1	0/16 (0%)	0
Psychiatric disorders
Agitation	0/36 (0%)	0	1/16 (6.3%)	1
Confusion	0/36 (0%)	0	1/16 (6.3%)	1
Renal and urinary disorders
Acute kidney injury	1/36 (2.8%)	1	0/16 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/36 (2.8%)	1	0/16 (0%)	0
Dyspnea	2/36 (5.6%)	2	1/16 (6.3%)	1
Nasal congestion	1/36 (2.8%)	1	0/16 (0%)	0
Pleural effusion	1/36 (2.8%)	2	2/16 (12.5%)	4
Respiratory failure	2/36 (5.6%)	3	0/16 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, Pneumonia	0/36 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Bullous dermatitis	1/36 (2.8%)	1	0/16 (0%)	0
Rash maculo-papular	2/36 (5.6%)	2	1/16 (6.3%)	1
Vascular disorders
Hypotension	0/36 (0%)	0	1/16 (6.3%)	1
Thromboembolic event	0/36 (0%)	0	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)		Radiofrequency Ablation/Cryoablation (RFA/CA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/36 (100%)		16/16 (100%)
Blood and lymphatic system disorders
Anemia	32/36 (88.9%)	181	15/16 (93.8%)	55
Blood and lymphatic system disorders - Other, aPTT decreased	1/36 (2.8%)	1	0/16 (0%)	0
Cardiac disorders
Sinus bradycardia	2/36 (5.6%)	2	0/16 (0%)	0
Sinus tachycardia	2/36 (5.6%)	2	1/16 (6.3%)	2
Endocrine disorders
Hyperthyroidism	1/36 (2.8%)	1	0/16 (0%)	0
Hypothyroidism	3/36 (8.3%)	3	1/16 (6.3%)	1
Eye disorders
Blurred vision	2/36 (5.6%)	2	2/16 (12.5%)	2
Cataract	1/36 (2.8%)	1	0/16 (0%)	0
Dry eye	1/36 (2.8%)	1	0/16 (0%)	0
Eye disorders - Other, Eye irritation	1/36 (2.8%)	1	0/16 (0%)	0
Eye disorders - Other, Eye itching	1/36 (2.8%)	1	0/16 (0%)	0
Glaucoma	1/36 (2.8%)	1	0/16 (0%)	0
Watering eyes	1/36 (2.8%)	1	0/16 (0%)	0
Gastrointestinal disorders
Abdominal distension	4/36 (11.1%)	7	2/16 (12.5%)	2
Abdominal pain	16/36 (44.4%)	24	7/16 (43.8%)	14
Ascites	4/36 (11.1%)	4	2/16 (12.5%)	2
Bloating	11/36 (30.6%)	14	2/16 (12.5%)	3
Colitis	2/36 (5.6%)	2	0/16 (0%)	0
Constipation	18/36 (50%)	29	6/16 (37.5%)	10
Diarrhea	9/36 (25%)	10	3/16 (18.8%)	5
Dry mouth	8/36 (22.2%)	9	0/16 (0%)	0
Dyspepsia	4/36 (11.1%)	4	0/16 (0%)	0
Dysphagia	1/36 (2.8%)	1	0/16 (0%)	0
Esophageal varices hemorrhage	1/36 (2.8%)	1	1/16 (6.3%)	1
Gastroesophageal reflux disease	1/36 (2.8%)	1	0/16 (0%)	0
Gastrointestinal disorders - Other, Abdominal discomfort	0/36 (0%)	0	1/16 (6.3%)	1
Gastrointestinal disorders - Other, Abdominal fullness	1/36 (2.8%)	1	0/16 (0%)	0
Gastrointestinal disorders - Other, Bloating	1/36 (2.8%)	1	0/16 (0%)	0
Gastrointestinal disorders - Other, Epigastric pain	1/36 (2.8%)	1	1/16 (6.3%)	1
Gastrointestinal disorders - Other, Indigestion	1/36 (2.8%)	1	0/16 (0%)	0
Gastroparesis	1/36 (2.8%)	2	0/16 (0%)	0
Hemorrhoids	1/36 (2.8%)	2	0/16 (0%)	0
Mucositis oral	3/36 (8.3%)	4	1/16 (6.3%)	1
Nausea	15/36 (41.7%)	18	8/16 (50%)	11
Vomiting	10/36 (27.8%)	13	6/16 (37.5%)	7
General disorders
Chills	4/36 (11.1%)	5	3/16 (18.8%)	3
Edema limbs	10/36 (27.8%)	15	4/16 (25%)	4
Fatigue	21/36 (58.3%)	36	12/16 (75%)	21
Fever	11/36 (30.6%)	13	9/16 (56.3%)	19
General disorders and administration site conditions - Other, Chest soreness	0/36 (0%)	0	1/16 (6.3%)	1
General disorders and administration site conditions - Other, Muscle spasm	0/36 (0%)	0	1/16 (6.3%)	1
General disorders and administration site conditions - Other, Numbness - left hand	1/36 (2.8%)	1	0/16 (0%)	0
Localized edema	1/36 (2.8%)	2	0/16 (0%)	0
Malaise	0/36 (0%)	0	2/16 (12.5%)	2
Non-cardiac chest pain	3/36 (8.3%)	3	1/16 (6.3%)	1
Pain	20/36 (55.6%)	36	7/16 (43.8%)	9
Immune system disorders
Allergic reaction	1/36 (2.8%)	1	0/16 (0%)	0
Autoimmune disorder	2/36 (5.6%)	3	2/16 (12.5%)	4
Immune system disorders - Other, Allergy development	1/36 (2.8%)	1	0/16 (0%)	0
Immune system disorders - Other, Skin rash near anus/groin	1/36 (2.8%)	1	0/16 (0%)	0
Infections and infestations
Catheter related infection	0/36 (0%)	0	1/16 (6.3%)	1
Hepatic infection	0/36 (0%)	0	1/16 (6.3%)	1
Infections and infestations - Other, Headaches and nose bleeds	1/36 (2.8%)	1	0/16 (0%)	0
Infections and infestations - Other, Staph	1/36 (2.8%)	1	0/16 (0%)	0
Infections and infestations - Other, Thrush	1/36 (2.8%)	1	0/16 (0%)	0
Infections and infestations - Other, Tinea cruris	1/36 (2.8%)	1	0/16 (0%)	0
Infections and infestations - Other, cold sore	0/36 (0%)	0	1/16 (6.3%)	1
Sepsis	0/36 (0%)	0	1/16 (6.3%)	1
Skin infection	2/36 (5.6%)	2	0/16 (0%)	0
Upper respiratory infection	1/36 (2.8%)	1	1/16 (6.3%)	1
Urinary tract infection	2/36 (5.6%)	2	2/16 (12.5%)	2
Injury, poisoning and procedural complications
Bruising	1/36 (2.8%)	1	0/16 (0%)	0
Fall	1/36 (2.8%)	1	1/16 (6.3%)	1
Fracture	1/36 (2.8%)	1	0/16 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	17/36 (47.2%)	32	7/16 (43.8%)	24
Alanine aminotransferase increased	24/36 (66.7%)	65	13/16 (81.3%)	50
Alkaline phosphatase increased	26/36 (72.2%)	96	13/16 (81.3%)	42
Aspartate aminotransferase increased	31/36 (86.1%)	128	13/16 (81.3%)	52
Blood bilirubin increased	14/36 (38.9%)	60	9/16 (56.3%)	25
CPK increased	2/36 (5.6%)	2	1/16 (6.3%)	1
Creatinine increased	16/36 (44.4%)	76	6/16 (37.5%)	11
Fibrinogen decreased	3/36 (8.3%)	6	0/16 (0%)	0
INR increased	2/36 (5.6%)	3	0/16 (0%)	0
Investigations - Other, Elevated TSH	2/36 (5.6%)	2	0/16 (0%)	0
Lipase increased	4/36 (11.1%)	4	0/16 (0%)	0
Lymphocyte count decreased	35/36 (97.2%)	243	13/16 (81.3%)	47
Neutrophil count decreased	6/36 (16.7%)	35	1/16 (6.3%)	2
Platelet count decreased	25/36 (69.4%)	82	6/16 (37.5%)	9
Serum amylase increased	21/36 (58.3%)	130	3/16 (18.8%)	7
Weight loss	4/36 (11.1%)	4	2/16 (12.5%)	2
White blood cell decreased	19/36 (52.8%)	100	3/16 (18.8%)	7
Metabolism and nutrition disorders
Acidosis	1/36 (2.8%)	1	0/16 (0%)	0
Anorexia	7/36 (19.4%)	7	6/16 (37.5%)	6
Dehydration	5/36 (13.9%)	6	3/16 (18.8%)	3
Hypercalcemia	11/36 (30.6%)	18	7/16 (43.8%)	15
Hyperglycemia	13/36 (36.1%)	47	5/16 (31.3%)	8
Hyperkalemia	8/36 (22.2%)	14	1/16 (6.3%)	1
Hypermagnesemia	9/36 (25%)	18	2/16 (12.5%)	3
Hypernatremia	6/36 (16.7%)	17	0/16 (0%)	0
Hyperuricemia	7/36 (19.4%)	43	3/16 (18.8%)	9
Hypoalbuminemia	28/36 (77.8%)	132	11/16 (68.8%)	26
Hypocalcemia	5/36 (13.9%)	9	2/16 (12.5%)	2
Hypoglycemia	2/36 (5.6%)	15	1/16 (6.3%)	1
Hypokalemia	11/36 (30.6%)	32	3/16 (18.8%)	3
Hypomagnesemia	7/36 (19.4%)	20	5/16 (31.3%)	6
Hyponatremia	30/36 (83.3%)	103	12/16 (75%)	25
Hypophosphatemia	19/36 (52.8%)	53	6/16 (37.5%)	12
Musculoskeletal and connective tissue disorders
Arthralgia	2/36 (5.6%)	4	0/16 (0%)	0
Arthritis	1/36 (2.8%)	1	0/16 (0%)	0
Back pain	6/36 (16.7%)	6	6/16 (37.5%)	6
Bone pain	3/36 (8.3%)	3	0/16 (0%)	0
Chest wall pain	1/36 (2.8%)	1	0/16 (0%)	0
Flank pain	2/36 (5.6%)	3	0/16 (0%)	0
Generalized muscle weakness	5/36 (13.9%)	5	2/16 (12.5%)	2
Musculoskeletal and connective tissue disorder - Other, Cramping - calves	0/36 (0%)	0	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorder - Other, Leg cramps	1/36 (2.8%)	1	0/16 (0%)	0
Myalgia	1/36 (2.8%)	3	1/16 (6.3%)	1
Myositis	1/36 (2.8%)	1	0/16 (0%)	0
Pain in extremity	4/36 (11.1%)	4	0/16 (0%)	0
Nervous system disorders
Depressed level of consciousness	1/36 (2.8%)	1	0/16 (0%)	0
Dizziness	4/36 (11.1%)	6	2/16 (12.5%)	2
Facial nerve disorder	1/36 (2.8%)	1	0/16 (0%)	0
Headache	7/36 (19.4%)	10	1/16 (6.3%)	1
Lethargy	1/36 (2.8%)	1	1/16 (6.3%)	1
Memory impairment	1/36 (2.8%)	1	0/16 (0%)	0
Nervous system disorders - Other, Tongue numbness	1/36 (2.8%)	1	0/16 (0%)	0
Paresthesia	3/36 (8.3%)	3	0/16 (0%)	0
Peripheral sensory neuropathy	1/36 (2.8%)	1	0/16 (0%)	0
Somnolence	1/36 (2.8%)	1	0/16 (0%)	0
Stroke	1/36 (2.8%)	1	0/16 (0%)	0
Psychiatric disorders
Confusion	2/36 (5.6%)	2	1/16 (6.3%)	1
Delirium	1/36 (2.8%)	1	0/16 (0%)	0
Depression	2/36 (5.6%)	2	0/16 (0%)	0
Insomnia	8/36 (22.2%)	8	4/16 (25%)	4
Renal and urinary disorders
Acute kidney injury	2/36 (5.6%)	2	0/16 (0%)	0
Hematuria	2/36 (5.6%)	2	1/16 (6.3%)	1
Urinary frequency	1/36 (2.8%)	1	0/16 (0%)	0
Urinary incontinence	1/36 (2.8%)	1	0/16 (0%)	0
Urinary retention	4/36 (11.1%)	4	0/16 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	1/36 (2.8%)	1	1/16 (6.3%)	1
Pelvic pain	1/36 (2.8%)	1	0/16 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/36 (2.8%)	4	1/16 (6.3%)	1
Cough	8/36 (22.2%)	8	3/16 (18.8%)	3
Dyspnea	7/36 (19.4%)	9	6/16 (37.5%)	13
Hoarseness	0/36 (0%)	0	2/16 (12.5%)	2
Hypoxia	1/36 (2.8%)	1	0/16 (0%)	0
Nasal congestion	1/36 (2.8%)	1	0/16 (0%)	0
Pharyngolaryngeal pain	1/36 (2.8%)	1	0/16 (0%)	0
Pleural effusion	2/36 (5.6%)	2	2/16 (12.5%)	3
Pneumonitis	1/36 (2.8%)	1	0/16 (0%)	0
Pneumothorax	1/36 (2.8%)	1	0/16 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, Pneumonia	0/36 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders - Other, Pulmonary abnormalities	1/36 (2.8%)	1	0/16 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, SOB	0/36 (0%)	0	1/16 (6.3%)	1
Sore throat	2/36 (5.6%)	2	2/16 (12.5%)	3
Wheezing	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders
Bullous dermatitis	1/36 (2.8%)	2	0/16 (0%)	0
Dry skin	7/36 (19.4%)	10	1/16 (6.3%)	1
Erythema multiforme	1/36 (2.8%)	1	0/16 (0%)	0
Hyperhidrosis	1/36 (2.8%)	1	1/16 (6.3%)	1
Papulopustular rash	1/36 (2.8%)	1	1/16 (6.3%)	1
Pruritus	13/36 (36.1%)	17	7/16 (43.8%)	8
Rash acneiform	1/36 (2.8%)	1	0/16 (0%)	0
Rash maculo-papular	15/36 (41.7%)	24	6/16 (37.5%)	8
Respiratory failure	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Abrasion on forehead	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Brown lesion/rash	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Cracked skin	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Dermatitis - penis	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Dermatitis - right buttocks	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Face swelling	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Itching	4/36 (11.1%)	4	3/16 (18.8%)	3
Skin and subcutaneous tissue disorders - Other, Itching arm and chest	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Itchy back	0/36 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders - Other, Keratosis; frontal scalp	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Mild rash on shoulder and sparsely on back	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Night sweats	0/36 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders - Other, Plaque rash	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Psoriasis; lower back	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, specify	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Redness to radiation area	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Skin discoloration	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Swelling - left leg	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, Swollen feet and ankles	0/36 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders - Other, Wound to gluteal folds	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, itching-anus	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, swelling- ankle	1/36 (2.8%)	1	0/16 (0%)	0
Skin and subcutaneous tissue disorders - Other, swelling- feet/legs	1/36 (2.8%)	1	0/16 (0%)	0
Skin hyperpigmentation	4/36 (11.1%)	4	0/16 (0%)	0
Skin hypopigmentation	1/36 (2.8%)	1	0/16 (0%)	0
Vascular disorders
Hematoma	1/36 (2.8%)	1	0/16 (0%)	0
Hot flashes	2/36 (5.6%)	2	0/16 (0%)	0
Hypertension	3/36 (8.3%)	5	0/16 (0%)	0
Hypotension	2/36 (5.6%)	2	1/16 (6.3%)	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.