Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02311361
• Collaborator: (none)
• Enrollment: 65
• Location: 1
• Arms: 6
• Actual Duration (Months): 69.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Background:

• Stereotactic body radiation therapy (SBRT) is used to treat cancer. It is a way of giving very focused beams of radiation to tumors. Researchers think that the drugs being used in this study might work better when combined with SBRT in people with pancreatic cancer.

Objective:

• To study the safety and effectiveness of Durvalumab (MEDI4736) and/or tremelimumab with SBRT.

Eligibility:

• People 18 and older who have pancreatic cancer that has not responded or to chemotherapy. They must be candidates for radiation but not resection.

Design:

• Participants will be screened with medical history and physical exam. They will have blood tests. Their tumor will be measured using computerized tomography (CT) or magnetic resonance imaging (MRI).

• Participants will have their tumor biopsied with a needle. They will have also have a biopsy after cycle 1.

• Participants will get 1 or 2 drugs in combination with the SBRT.

• For MEDI4736, the duration of each cycle will be 28-days. Participants will get the drug through an intravenous (IV) infusion twice in each cycle (Days 1 and 15).

• For tremelimumab, the duration of the first 6 cycles will each last 28 days. Then the duration of the last 3 cycles will change to 12 weeks. Participants will get the drug through an IV once in each cycle.

• All participants will have SBRT. Some will get 1 dose of radiation and some will get 5. CT scans will map their tumor.

• Participants will have medical history, physical exam, and blood tests in each cycle. They will have a CT scan or MRI every 8 weeks. Cycles will continue for up to 12 months.

• Participants will be contacted yearly for follow-up.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Neoplasms; Pancreatic Cancer; Cancer of Pancreas; Cancer of the Pancreas; Pancreas Cancer	Biological: Durvalumab; Biological: Tremelimumab; Radiation: Sterostatic body radiation therapy (SBRT)	Phase 1/Phase 2

Detailed Description

Background:

Tremelimumab is a monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Anti-CTLA4 therapy has been shown to enhance anti-tumor immunity by blocking tumor-induced immune suppression of cytotoxic T cells.

Durvalumab is a human monoclonal antibody directed against Programmed death-ligand 1 (PD-L1). Blockage of ligation between PD-L1 and Programmed cell death protein 1 (PD1) induces local immune activation and prevent anergy and exhaustion of effectors T-cells.

Several studies have documented an increase in peripheral antitumor immunity following radiation. This effect is evidently too weak to be clinically relevant, but has the potential to be boosted by immune modulation.

The underlying hypothesis of this study is that the effect of Immune Checkpoint inhibitor (Durvalumab with or without Tremelimumab) treatment can be enhanced by radiation in patients with advanced pancreatic carcinoma.

Objective:

To determine the safety, tolerability and feasibility of immune checkpoint inhibition [comprising either Durvalumab alone, or combined Durvalumab and Tremelimumab] in combination with stereotactic body radiation therapy (SBRT) in patients with unresectable pancreatic cancer.

Eligibility:

Histologically confirmed metastatic pancreatic cancer with primary in-situ (or locally-recurrent) with at least 1 measurable metastatic lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and accessible for biopsy. There is no limit to the number of prior chemotherapy regimens received.

Patients must be greater than or equal to 18 years of age and have a performance status (Eastern Cooperative Oncology Group (ECOG)) less than or equal to 1

Life expectancy of greater than 3 months.

Acceptable organ and bone marrow function.

Patients must not have had standard of care chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study. For recent experimental therapies a 28 day period of time must have elapsed before commencing protocol treatment.

No active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome; Graves disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within the past 3 years prior to the start of treatment.

No active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. No active or history of systemic lupus erythematosus, Wegeners granulomatosis.

Design:

Subjects will be assigned to 4 arms

Anti-PDL1 (Durvalumab) in combination with radiation (8 Gray (Gy) in fraction)

• Anti-PDL1 (Durvalumab) in combination with radiation (5 Gy in 5 fractions)

Anti-PDL1 (Durvalumab) and anti-CTLA4 (Tremelimumab) in combination with radiation (8 Gy in 1 fractions)

• Anti-PDL1 (Durvalumab) and anti-CTLA4 (Tremelimumab) in combination with radiation (5 Gy in 5 fractions).

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Immune Checkpoint Inhibition (Durvalumab With or Without Tremelimumab) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer
• Actual Study Start Date: Mar 25, 2015
• Actual Primary Completion Date: Oct 23, 2019
• Actual Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Durvalumab + 8 Gray (Gy) in 1 fraction Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction	Biological: Durvalumab; 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.; Other Names: MEDI4736 ; Radiation: Sterostatic body radiation therapy (SBRT); 8 Gray (Gy) x 1; 5Gy x 5; Other Names: Sterostatic ablative radiotherapy
Experimental: Durvalumab +5 Gy in 5 fractions Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions	Biological: Durvalumab; 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.; Other Names: MEDI4736 ; Radiation: Sterostatic body radiation therapy (SBRT); 8 Gray (Gy) x 1; 5Gy x 5; Other Names: Sterostatic ablative radiotherapy
Experimental: Tremelimumab + 8 Gy in 1 fraction Cohort 3/Dose Level B1 (was removed with Amendment A) Tremelimumab + 8 Gy in 1 fraction	Biological: Tremelimumab; 75 mg IV, every 4 weeks for 16 weeks; Other Names: Ticilmumab ; Radiation: Sterostatic body radiation therapy (SBRT); 8 Gray (Gy) x 1; 5Gy x 5; Other Names: Sterostatic ablative radiotherapy
Experimental: Tremelimumab + 5 Gy in 5 fractions Cohort 4/Dose Level B2 (was removed with Amendment A) Tremelimumab + 5 Gy in 5 fractions	Biological: Tremelimumab; 75 mg IV, every 4 weeks for 16 weeks; Other Names: Ticilmumab ; Radiation: Sterostatic body radiation therapy (SBRT); 8 Gray (Gy) x 1; 5Gy x 5; Other Names: Sterostatic ablative radiotherapy
Experimental: Durvalumab +Tremelimumab + 8 Gy in 1 fraction Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction	Biological: Durvalumab; 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.; Other Names: MEDI4736 ; Biological: Tremelimumab; 75 mg IV, every 4 weeks for 16 weeks; Other Names: Ticilmumab ; Radiation: Sterostatic body radiation therapy (SBRT); 8 Gray (Gy) x 1; 5Gy x 5; Other Names: Sterostatic ablative radiotherapy
Experimental: Durvalumab +Tremelimumab +5 Gy in 5 fractions Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions	Biological: Durvalumab; 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.; Other Names: MEDI4736 ; Biological: Tremelimumab; 75 mg IV, every 4 weeks for 16 weeks; Other Names: Ticilmumab ; Radiation: Sterostatic body radiation therapy (SBRT); 8 Gray (Gy) x 1; 5Gy x 5; Other Names: Sterostatic ablative radiotherapy

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug [Participants were assessed from the start of study treatment at Cycle 1 then after every cycle (1 cycle = 28 days) of protocol treatment until 30 days after they were taken off treatment, approximately 4.0 months.]

   Adverse Events (AEs) are reported by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1=Mild, Grade 2= Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Fatal.

Secondary Outcome Measures

1. Plasma Pharmacokinetic (PK) [30 days after treatment]

   Drug level in blood

2. Percentage of Participants With 6-month Overall Survival [6 month]

   Participants who survived at least 6 months after therapy.

3. Overall Survival [From study entry to death or date of last contact, whichever occurs first, up to 2 years of follow-up]

   Amount of time participants survived after therapy.

4. Tumor Response Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Measured by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) [At screening then every 8 weeks until disease progression or patient is taken off the trial, whichever comes first, approximately 6 months.]

   Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.

5. Progression Free Survival (PFS) [From study entry to disease progression, death or date of last contact, whichever occurs first, an average of 6 months]

   PFS is the defined as the median amount of time subject survives without disease progression after treatment. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). NOTE: While RECIST Progressive Disease (PD) will be noted and recorded the immune-related (IR) RECIST criteria will be applied to determine discontinuation of study treatment. For modified Immune-Related Response Criteria (irRC), only target and measurable lesions are taken into account.

6. Number of Participants With Serious and 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 18 months and 4 days for Cohort 1/Dose Level A1, 23 months and 29 days for Cohort 2/Dose Level A2, 32 months and 19 days for Cohort C/Dose Level C1, and 44 months and 18 days for Cohort C/Dose]

   Here is the count of participants with serious and 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 to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

• Patients must have histopathological confirmation of pancreatic adenocarcinoma prior to entering this study by the Laboratory of Pathology of the National Cancer Institute (NCI) to entering this study by the Laboratory of Pathology of the NCI prior to entering this study

• Patients must have disease that is not amenable to potentially curative resection. Primary in-situ (or locally-recurrent) tumor must be present and, in the opinion of radiation oncology, be amenable to radiation therapy as planned in the protocol. Each case will be discussed at GI tumor board with multidisciplinary team.

• Patients must have at least 1 measurable metastatic lesion by Response Evaluation in Solid Tumors (RECIST) 1.1 criteria.

• There is no limit to the number of prior chemotherapy regimens received. Patients must have received at least one line of prior systemic chemotherapy for advanced unresectable and/or metastatic disease.

• Age greater than or equal to 18 years

• Life expectancy of greater than 3 months.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

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

• absolute neutrophil count - > 1,000/mcL

• Platelets - greater than or equal to 100,000/mcL

• total bilirubin - Bili should be less than or equal to 2 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin less than 3.0 mg/dL)

• serum albumin - greater than or equal 2.5 g/dL

Patients are eligible with alanine aminotransferase (ALT) or aspartate aminotransaminase (AST) up to 3 x ULN. (up to 5 x ULN if liver metastases present)

--Creatinine - < 2X institution upper limit of normal

OR

--creatinine clearance - >45 mL/min/1.73 m(2), for patients with creatinine levels above institutional normal

• 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.

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

EXCLUSION CRITERIA:

• Malignant ascites that is clinically detectable by physical examination or is symptomatic. Evidence of radiographic ascites that is not clinically significant will not be an exclusion criterion.

• Any prior Grade greater than or equal to 3 imAE while receiving immunotherapy, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment, or any unresolved imAE > Grade 1. Note: Active or history of vitiligo will not be a basis for exclusion.

• Patients must not have had standard of care chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study. Note: Local surgeries for isolated lesions for palliative intent are acceptable. For recent experimental therapies a 28 day period of time must have elapsed before commencing protocol treatment.

• 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.

• Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from Durvalumab (MEDI4736) or tremelimumab, or compromise the ability of the subject to give written informed consent.

• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome; Graves disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:

• Subjects with vitiligo or alopecia

• Requirement for intermittent use of bronchodilators or local steroid injections

• Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment

• History of primary immunodeficiency or history of active tuberculosis. Note: Latent tuberculosis will not be a basis for exclusion.

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

• 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.

• True positive test results for hepatitis A (Immunoglobulin M (IgM) positive). Subjects with a history of hepatitis A with Immunoglobulin G (IgG) blood test are not excluded. True positive test results hepatitis B, or C infection.

• 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 Wegeners granulomatosis.

• Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 and tremelimumab. The following are exceptions to this criterion:

• Intranasal, inhaled, and topical steroids

• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent

• Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication)

• History of sarcoidosis syndrome.

• Patients should not be vaccinated with live attenuated vaccines within 1 month of starting Tremelimumab and MEDI4736 treatment. Subjects, if enrolled, should not receive live vaccine during the study and 180 days after the last dose of both drugs.

• Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and Tremelimumab or MEDI4736. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that Tremelimumab or MEDI4736 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events.

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

• Pregnancy and breast feeding are exclusion factors. The effects of Tremelimumab and MEDI4736 on the developing human fetus are unknown. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 180 days (female patients) or 90 days (male patients) after the end of the treatment. In addition male patients must refrain from sperm donation for 90 days after the final dose of investigational product. Female patients must refrain from egg cell donation for 180 days after the final dose of investigational product. 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.

• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	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 - Aug 24, 2018
• Informed Consent Form: Arms A1 and A2 Consent - Aug 29, 2018
• Informed Consent Form: Arms C1 and C2 Consent - Aug 29, 2018

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Moertel CG, Childs DS Jr, Reitemeier RJ, Colby MY Jr, Holbrook MA. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969 Oct 25;2(7626):865-7.
• Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. Epub 2007 Apr 23.
• Reyes-Gibby CC, Chan W, Abbruzzese JL, Xiong HQ, Ho L, Evans DB, Varadhachary G, Bhat S, Wolff RA, Crane C. Patterns of self-reported symptoms in pancreatic cancer patients receiving chemoradiation. J Pain Symptom Manage. 2007 Sep;34(3):244-52. Epub 2007 May 21.

• Responsible Party: Tim Greten, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02311361
• Other Study ID Numbers: 150027; 15-C-0027
• First Posted: Dec 8, 2014
• Last Update Posted: Apr 20, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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): Anti-PDL1; Anti-CTLA4; Streostatic Body Radiation Therapy (SBRT); Monoclonal Antibody; Antitumor Immunity
• Additional relevant MeSH terms: Pancreatic Neoplasms; Durvalumab; Tremelimumab

Study Results

Participant Flow

Arm/Group Title	Durvalumab + 8 Gray (Gy) in 1 Fraction	Durvalumab +5 Gy in 5 Fractions	Durvalumab +Tremelimumab + 8 Gy in 1 Fraction	Durvalumab +Tremelimumab +5 Gy in 5 Fractions
Arm/Group Description	Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
Period Title: Overall Study
STARTED	14	11	19	21
Received Radiation Therapy Only	0	1	1	1
COMPLETED	14	10	19	20
NOT COMPLETED	0	1	0	1

Baseline Characteristics

Arm/Group Title	Durvalumab + 8 Gray (Gy) in 1 Fraction	Durvalumab +5 Gy in 5 Fractions	Durvalumab +Tremelimumab + 8 Gy in 1 Fraction	Durvalumab +Tremelimumab +5 Gy in 5 Fractions	Total
Arm/Group Description	Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Total of all reporting groups
Overall Participants	14	11	19	21	65
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	10 71.4%	6 54.5%	13 68.4%	12 57.1%	41 63.1%
>=65 years	4 28.6%	5 45.5%	6 31.6%	9 42.9%	24 36.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.75 (9.27)	61.70 (6.36)	64.26 (11.77)	65.31 (9.58)	63.26 (9.25)
Sex: Female, Male (Count of Participants)
Female	7 50%	5 45.5%	9 47.4%	4 19%	25 38.5%
Male	7 50%	6 54.5%	10 52.6%	17 81%	40 61.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	1 5.3%	0 0%	1 1.5%
Not Hispanic or Latino	14 100%	11 100%	18 94.7%	21 100%	64 98.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 7.1%	0 0%	0 0%	0 0%	1 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 7.1%	0 0%	3 15.8%	4 19%	8 12.3%
White	11 78.6%	11 100%	16 84.2%	17 81%	55 84.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 7.1%	0 0%	0 0%	0 0%	1 1.5%
Region of Enrollment (Count of Participants)
United States	14 100%	11 100%	19 100%	21 100%	65 100%

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug
Description	Adverse Events (AEs) are reported by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1=Mild, Grade 2= Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Fatal.
Time Frame	Participants were assessed from the start of study treatment at Cycle 1 then after every cycle (1 cycle = 28 days) of protocol treatment until 30 days after they were taken off treatment, approximately 4.0 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A Dose Level A1	Cohort A Dose Level A2	Cohort C Dose Level C1	Cohort C Dose Level C2
Arm/Group Description	Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
Measure Participants	14	10	19	20
Grade 1 Abdominal pain	0	0	0	1
Grade 1 Alanine aminotransferase increased	1	0	0	5
Grade 1 Alkaline Phosphatase increased	0	2	0	2
Grade 1 Anemia	3	3	9	9
Grade 1 Anorexia	1	0	0	3
Grade 1 Atrial fibrillation	0	0	0	1
Grade 1 Aspartate aminotransferase increased	1	0	1	6
Grade 1 Back pain	0	0	0	1
Grade 1 Blood bilirubin increased	0	0	1	1
Grade 1 Cough	0	0	0	1
Grade 1 Creatinine increased	0	0	0	1
Grade 1 Diarrhea	0	1	1	7
Grade 1 Dizziness	0	0	0	1
Grade 1 Dry mouth	1	0	0	0
Grade 1 Dysgeusia	0	0	1	0
Grade 1 Endocrine disorders,Other, Elevated T3, T4	0	0	1	0
Grade 1 Eye disorders - decr. in near vision,bilat	0	1	0	0
Grade 1 - Fatigue	1	2	0	7
Grade 1 Fever	1	1	1	1
Grade 1 Headache	0	2	0	0
Grade 1 Hemorrhoidal hemorrhage	1	0	0	0
Grade 1 Hoarseness	0	0	1	0
Grade 1 Hyperglycemia	0	0	2	0
Grade 1 - Hyperkalemia	0	0	0	1
Grade 1 Hyperuricemia	0	0	0	1
Grade 1 Hypoalbuminemia	0	0	0	5
Grade 1 Hypocalcemia	0	0	0	1
Grade 1 - Hyponatremia	2	0	3	4
Grade 1 Hypothyroidism	0	0	0	1
Grade 1 Infusion related reaction	0	0	0	2
Grade 1 Lymphocyte count decreased	15	20	17	26
Grade 1 Mucositis	0	0	0	1
Grade 1 Musculoskeletal & connective tissue	0	3	0	0
Grade 1 Nausea	0	1	3	2
Grade 1 Neutrophil count decreased	0	0	0	1
Grade 1 Pain	0	0	0	1
Grade 1 Platelet count decreased	2	0	7	13
Grade 1 Pruritis	1	1	2	3
Grade 1 Rash maculo-papular	0	1	1	2
Grade 1 Serum amylase increased	0	0	0	3
Grade 1 - Skin/subc tissue disorder - Night sweats	0	0	1	1
Grade 1 Skin/subc tissue disorder - Rash	0	0	1	0
Grade 1 Skin/subc tissue - Psoriasis	0	1	0	0
Grade 1 Skin/subc tissue disorder - Itching	0	1	1	0
Grade 1 Skin/subc tissue disorder-Skinpeeling hand	0	0	1	0
Grade 1 Vertigo	0	1	0	0
Grade 1 Vomiting	0	0	1	4
Grade 1 Weight loss	0	0	0	1
Grade 1 White blood cell decreased	1	4	1	7
Grade 2 Abdominal pain	0	0	0	1
Grade 2 Anemia	3	1	9	10
Grade 2 Anorexia	0	0	0	2
Grade 2 Autoimmune disorder	0	0	0	1
Grade 2 Diarrhea	0	1	2	4
Grade 2 Dysgeusia	0	0	0	1
Grade 2 Endocrine disorders - TSH elev-Hypothyroid	0	0	1	0
Grade 2 Fatigue	0	0	2	5
Grade 2 Fecal incontinence	0	1	0	0
Grade 2 Fever	0	0	0	1
Grade 2 Gastroesophageal reflux disease	0	1	0	0
Grade 2 Hyperglycemia	0	0	1	0
Grade 2 Hypoalbuminemia	0	0	0	1
Grade 2 Hypothyroidism	0	0	1	0
Grade 2 Hypophosphatemia	1	0	0	0
Grade 2 Infusion related reaction	0	0	1	0
Grade 2 Lymphocyte count decreased	7	19	15	30
Grade 2 Malaise	0	0	0	2
Grade 2 Nausea	0	0	0	3
Grade 2 Neutrophil count decreased	0	0	2	1
Grade 2 Platelet count decreased	0	0	1	2
Grade 2 Rash maculo-papular	0	0	0	1
Grade 2 Weight loss	0	0	0	2
Grade 2 White blood cell count	0	2	1	0
Grade 3 Anemia	0	0	2	3
Grade 3 Anorexia	0	0	0	1
Grade 3 Colitis	0	0	0	2
Grade 3 Dehydration	0	0	0	3
Grade 3 Diarrhea	0	0	0	3
Grade 3 Fatigue	0	0	1	1
Grade 3 Hyperthyroidism	0	0	0	1
Grade 3 Lymphocyte count decreased	3	7	6	18
Grade 3 Nausea	0	0	0	2
Grade 3 Serum amylase increased	0	0	1	0
Grade 3 Vomiting	0	0	0	2
Grade 4 Lymphocyte count decreased	0	0	2	2

2. Secondary Outcome

Title	Plasma Pharmacokinetic (PK)
Description	Drug level in blood
Time Frame	30 days after treatment

Outcome Measure Data

Analysis Population Description

The pharmacokinetic studies were not done since the company were not interested in this after the samples were collected

Arm/Group Title	Cohort A Dose Level A1	Cohort A Dose Level A2	Cohort C Dose Level C1	Cohort C Dose Level C2
Arm/Group Description	Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
Measure Participants	0	0	0	0

3. Secondary Outcome

Title	Percentage of Participants With 6-month Overall Survival
Description	Participants who survived at least 6 months after therapy.
Time Frame	6 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A Dose Level A1	Cohort A Dose Level A2	Cohort C Dose Level C1	Cohort C Dose Level C2
Arm/Group Description	Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
Measure Participants	14	10	19	20
Number [percentage of participants]	26 185.7%	58 527.3%	12 63.2%	40 190.5%

4. Secondary Outcome

Title	Overall Survival
Description	Amount of time participants survived after therapy.
Time Frame	From study entry to death or date of last contact, whichever occurs first, up to 2 years of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A Dose Level A1	Cohort A Dose Level A2	Cohort C Dose Level C1	Cohort C Dose Level C2
Arm/Group Description	Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
Measure Participants	14	10	19	20
Median (Full Range) [Months]	3.3	9.0	2.1	4.2

5. Secondary Outcome

Title	Tumor Response Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Measured by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)
Description	Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
Time Frame	At screening then every 8 weeks until disease progression or patient is taken off the trial, whichever comes first, approximately 6 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A Dose Level A1	Cohort A Dose Level A2	Cohort C Dose Level C1	Cohort C Dose Level C2
Arm/Group Description	Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
Measure Participants	14	10	19	20
Complete Response	0 0%	0 0%	0 0%	0 0%
Partial Response	1 7.1%	0 0%	0 0%	1 4.8%
Stable Disease	3 21.4%	4 36.4%	2 10.5%	5 23.8%
Progressive Disease	4 28.6%	4 36.4%	6 31.6%	10 47.6%

6. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is the defined as the median amount of time subject survives without disease progression after treatment. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). NOTE: While RECIST Progressive Disease (PD) will be noted and recorded the immune-related (IR) RECIST criteria will be applied to determine discontinuation of study treatment. For modified Immune-Related Response Criteria (irRC), only target and measurable lesions are taken into account.
Time Frame	From study entry to disease progression, death or date of last contact, whichever occurs first, an average of 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A Dose Level A1	Cohort A Dose Level A2	Cohort C Dose Level C1	Cohort C Dose Level C2
Arm/Group Description	Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
Measure Participants	14	10	19	20
Median (Full Range) [Months]	1.7	2.5	0.9	2.3

7. Secondary Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Description	Here is the count of participants with serious and 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 18 months and 4 days for Cohort 1/Dose Level A1, 23 months and 29 days for Cohort 2/Dose Level A2, 32 months and 19 days for Cohort C/Dose Level C1, and 44 months and 18 days for Cohort C/Dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Durvalumab + 8 Gray (Gy) in 1 Fraction	Durvalumab +5 Gy in 5 Fractions	Durvalumab +Tremelimumab + 8 Gy in 1 Fraction	Durvalumab +Tremelimumab +5 Gy in 5 Fractions
Arm/Group Description	Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5	Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
Measure Participants	14	11	19	20
Count of Participants [Participants]	14 100%	10 90.9%	19 100%	20 95.2%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 18 months and 4 days for Cohort 1/Dose Level A1, 23 months and 29 days for Cohort 2/Dose Level A2, 32 months and 19 days for Cohort C/Dose Level C1, and 44 months and 18 days for Cohort C/Dose Level C2.
Adverse Event Reporting Description	One patient did not get treated in Cohort 2/Dose Level A2 and Cohort C/Dose Level C2.
Arm/Group Title	Durvalumab + 8 Gray (Gy) in 1 Fraction		Durvalumab +5 Gy in 5 Fractions		Durvalumab +Tremelimumab + 8 Gy in 1 Fraction		Durvalumab +Tremelimumab +5 Gy in 5 Fractions
Arm/Group Description	Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5		Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5		Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5		Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions Durvalumab: 10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks. Tremelimumab: 75 mg IV, every 4 weeks for 16 weeks Sterostatic body radiation therapy (SBRT): 8 Gray (Gy) x 1; 5Gy x 5
All Cause Mortality
	Durvalumab + 8 Gray (Gy) in 1 Fraction		Durvalumab +5 Gy in 5 Fractions		Durvalumab +Tremelimumab + 8 Gy in 1 Fraction		Durvalumab +Tremelimumab +5 Gy in 5 Fractions
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100%)		8/11 (72.7%)		2/19 (10.5%)		3/20 (15%)
Serious Adverse Events
	Durvalumab + 8 Gray (Gy) in 1 Fraction		Durvalumab +5 Gy in 5 Fractions		Durvalumab +Tremelimumab + 8 Gy in 1 Fraction		Durvalumab +Tremelimumab +5 Gy in 5 Fractions
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/14 (42.9%)		2/11 (18.2%)		11/19 (57.9%)		12/20 (60%)
Cardiac disorders
Cardiac disorders - Other, pulm embolism	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Sinus tachycardia	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Endocrine disorders
Hyperthyroidism	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders
Dysphagia	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Small intestinal obstruction	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Ascites	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Diarrhea	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	2/20 (10%)	2
Duodenal obstruction	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Gastrointestinal disorders - Other, Abdominal cramping	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Gastroparesis	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Abdominal pain	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	2
Colitis	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	2/20 (10%)	2
Gastrointestinal disorders - Other, Liver abscess	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	2
Ileal obstruction	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Nausea	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	3/20 (15%)	3
Upper gastrointestinal hemorrhage	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Vomiting	0/14 (0%)	0	0/11 (0%)	0	2/19 (10.5%)	2	2/20 (10%)	2
General disorders
Death NOS	3/14 (21.4%)	3	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Fatigue	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	2/20 (10%)	2
Malaise	2/14 (14.3%)	2	1/11 (9.1%)	1	0/19 (0%)	0	2/20 (10%)	2
Pain	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Infections and infestations
Infections and infestations - Other, specify	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Catheter related infection	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Endocarditis infective	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Sepsis	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Urinary tract infection	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Infections and infestations - Other, pneumonia	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Investigations
Alanine aminotransferase increased	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Aspartate aminotransferase increased	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Blood bilirubin increased	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	3/20 (15%)	5
Metabolism and nutrition disorders
Dehydration	1/14 (7.1%)	1	0/11 (0%)	0	4/19 (21.1%)	4	7/20 (35%)	8
Alkalosis	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Hyponatremia	0/14 (0%)	0	0/11 (0%)	0	2/19 (10.5%)	2	1/20 (5%)	1
Anorexia	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Hypoalbuminemia	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	2/20 (10%)	2
Hypokalemia	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	2
Musculoskeletal and connective tissue disorders
Chest pain - cardiac	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, death	1/14 (7.1%)	1	0/11 (0%)	0	2/19 (10.5%)	2	3/20 (15%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Nervous system disorders
Stroke	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Dizziness	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/14 (7.1%)	1	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Respiratory failure	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Pleural effusion	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Vascular disorders
Hypertension	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Thromboembolic event	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Durvalumab + 8 Gray (Gy) in 1 Fraction		Durvalumab +5 Gy in 5 Fractions		Durvalumab +Tremelimumab + 8 Gy in 1 Fraction		Durvalumab +Tremelimumab +5 Gy in 5 Fractions
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100%)		10/11 (90.9%)		19/19 (100%)		20/20 (100%)
Blood and lymphatic system disorders
Lymph node pain	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Blood and lymphatic system disorders - Other, Increased PT	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Anemia	10/14 (71.4%)	28	9/11 (81.8%)	30	15/19 (78.9%)	37	16/20 (80%)	46
Cardiac disorders
Paroxysmal atrial tachycardia	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Ventricular tachycardia	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Atrial fibrillation	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Sinus tachycardia	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	3/20 (15%)	3
Ear and labyrinth disorders
Hearing impaired	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Ear pain	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Endocrine disorders
Endocrine disorders - Other, Elevated T3, T4	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Hypothyroidism	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	1/20 (5%)	1
Endocrine disorders - Other, TSH elevated - hypothyroidsim	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Eye disorders
Blurred vision	1/14 (7.1%)	1	1/11 (9.1%)	2	0/19 (0%)	0	0/20 (0%)	0
Eye disorders - Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Retinal vascular disorder	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Gastrointestinal disorders
Colitis	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Dry mouth	2/14 (14.3%)	2	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Flatulence	1/14 (7.1%)	1	1/11 (9.1%)	1	1/19 (5.3%)	1	1/20 (5%)	1
Gastrointestinal disorders - Other,bile duct obstruction	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Small intestinal obstruction	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Dysphagia	0/14 (0%)	0	2/11 (18.2%)	4	0/19 (0%)	0	0/20 (0%)	0
Fecal incontinence	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Gastroparesis	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Hemorrhoids	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Rectal pain	1/14 (7.1%)	1	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Vomiting	3/14 (21.4%)	3	4/11 (36.4%)	4	6/19 (31.6%)	7	6/20 (30%)	7
Abdominal distension	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Abdominal pain	2/14 (14.3%)	5	4/11 (36.4%)	10	5/19 (26.3%)	11	12/20 (60%)	25
Anal hemorrhage	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Ascites	3/14 (21.4%)	3	0/11 (0%)	0	7/19 (36.8%)	7	4/20 (20%)	5
Bloating	2/14 (14.3%)	2	4/11 (36.4%)	4	2/19 (10.5%)	2	2/20 (10%)	2
Constipation	5/14 (35.7%)	5	5/11 (45.5%)	9	4/19 (21.1%)	4	8/20 (40%)	9
Diarrhea	3/14 (21.4%)	3	5/11 (45.5%)	9	8/19 (42.1%)	9	8/20 (40%)	19
Dysgeusia	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Dyspepsia	0/14 (0%)	0	2/11 (18.2%)	2	0/19 (0%)	0	4/20 (20%)	7
Gastroesophageal reflux disease	1/14 (7.1%)	1	1/11 (9.1%)	1	1/19 (5.3%)	1	1/20 (5%)	1
Hemorrhoidal hemorrhage	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Ileal obstruction	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Mucositis oral	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Nausea	4/14 (28.6%)	6	3/11 (27.3%)	5	9/19 (47.4%)	12	7/20 (35%)	9
Oral dysesthesia	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Periodontal disease	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders - Other, Fullness/Bloating	0/14 (0%)	0	1/11 (9.1%)	2	0/19 (0%)	0	0/20 (0%)	0
Gastrointestinal disorders - Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Gastrointestinal disorders - Other, Specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Gastrointestinal disorders - Other, Abdominal cramping	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders - Other, specify	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders - Other, Upper abdominal soreness	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders - Other, specify	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
General disorders
Edema trunk	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Chills	1/14 (7.1%)	1	0/11 (0%)	0	1/19 (5.3%)	1	3/20 (15%)	3
Edema limbs	2/14 (14.3%)	3	3/11 (27.3%)	6	4/19 (21.1%)	5	2/20 (10%)	2
Fatigue	7/14 (50%)	9	8/11 (72.7%)	10	7/19 (36.8%)	9	15/20 (75%)	22
Fever	4/14 (28.6%)	5	3/11 (27.3%)	4	3/19 (15.8%)	3	5/20 (25%)	11
Generalized muscle weakness	2/14 (14.3%)	4	1/11 (9.1%)	1	2/19 (10.5%)	4	3/20 (15%)	3
Infusion related reaction	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	2
Lethargy	0/14 (0%)	0	1/11 (9.1%)	2	1/19 (5.3%)	1	0/20 (0%)	0
Malaise	2/14 (14.3%)	2	1/11 (9.1%)	1	0/19 (0%)	0	2/20 (10%)	2
Pain	8/14 (57.1%)	14	4/11 (36.4%)	8	2/19 (10.5%)	3	5/20 (25%)	6
General disorders and administration site conditions - Other, weakness	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Hepatobiliary disorders
Portal vein thrombosis	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Immune system disorders
Autoimmune disorder	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Infections and infestations
Infections and infestations - Other, Strep and haemophilus	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Bladder infection	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Lung infection	0/14 (0%)	0	0/11 (0%)	0	2/19 (10.5%)	2	0/20 (0%)	0
Urinary tract infection	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	3/20 (15%)	3
Wound infection	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Infections and infestations - Other, C-diff. infection	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Infections and infestations - Other, yeast infection - rectal area	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Infections and infestations - Other, specify	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Injury, poisoning and procedural complications
Fall	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	1/20 (5%)	1
Postoperative hemorrhage	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	2
Investigations
Lipase increased	1/14 (7.1%)	1	1/11 (9.1%)	2	0/19 (0%)	0	0/20 (0%)	0
Weight gain	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Anorexia	8/14 (57.1%)	10	1/11 (9.1%)	1	7/19 (36.8%)	9	9/20 (45%)	17
Platelet count decreased	7/14 (50%)	17	9/11 (81.8%)	15	6/19 (31.6%)	13	10/20 (50%)	30
Serum amylase increased	1/14 (7.1%)	2	2/11 (18.2%)	2	3/19 (15.8%)	3	2/20 (10%)	9
Weight loss	1/14 (7.1%)	1	2/11 (18.2%)	2	3/19 (15.8%)	3	6/20 (30%)	7
White blood cell decreased	4/14 (28.6%)	11	5/11 (45.5%)	16	2/19 (10.5%)	10	5/20 (25%)	13
Activated partial thromboplastin time prolonged	10/14 (71.4%)	23	6/11 (54.5%)	19	3/19 (15.8%)	5	8/20 (40%)	10
Alanine aminotransferase increased	6/14 (42.9%)	15	2/11 (18.2%)	2	6/19 (31.6%)	7	11/20 (55%)	30
Alkaline phosphatase increased	9/14 (64.3%)	24	5/11 (45.5%)	9	9/19 (47.4%)	15	18/20 (90%)	43
Aspartate aminotransferase increased	7/14 (50%)	15	3/11 (27.3%)	6	9/19 (47.4%)	13	12/20 (60%)	25
Blood bilirubin increased	6/14 (42.9%)	14	2/11 (18.2%)	2	6/19 (31.6%)	10	5/20 (25%)	15
Creatinine increased	3/14 (21.4%)	6	1/11 (9.1%)	1	1/19 (5.3%)	1	3/20 (15%)	5
INR increased	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Lymphocyte count decreased	12/14 (85.7%)	44	10/11 (90.9%)	54	16/19 (84.2%)	52	18/20 (90%)	92
Neutrophil count decreased	1/14 (7.1%)	1	1/11 (9.1%)	4	2/19 (10.5%)	2	1/20 (5%)	4
Platelet count decreased	7/14 (50%)	17	8/11 (72.7%)	13	5/19 (26.3%)	13	12/20 (60%)	32
Metabolism and nutrition disorders
Hypermagnesemia	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Dehydration	2/14 (14.3%)	3	2/11 (18.2%)	2	5/19 (26.3%)	5	5/20 (25%)	5
Hypercalcemia	2/14 (14.3%)	7	0/11 (0%)	0	5/19 (26.3%)	11	4/20 (20%)	11
Hyperglycemia	0/14 (0%)	0	0/11 (0%)	0	2/19 (10.5%)	3	3/20 (15%)	5
Hyperkalemia	1/14 (7.1%)	2	1/11 (9.1%)	1	0/19 (0%)	0	3/20 (15%)	5
Hypernatremia	0/14 (0%)	0	2/11 (18.2%)	2	1/19 (5.3%)	5	2/20 (10%)	2
Hyperuricemia	1/14 (7.1%)	1	0/11 (0%)	0	2/19 (10.5%)	3	4/20 (20%)	6
Hypoalbuminemia	11/14 (78.6%)	24	8/11 (72.7%)	19	13/19 (68.4%)	31	16/20 (80%)	37
Hypocalcemia	2/14 (14.3%)	4	3/11 (27.3%)	3	4/19 (21.1%)	9	4/20 (20%)	6
Hypoglycemia	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	3
Hypokalemia	6/14 (42.9%)	18	3/11 (27.3%)	6	1/19 (5.3%)	1	8/20 (40%)	11
Hypomagnesemia	4/14 (28.6%)	8	2/11 (18.2%)	2	5/19 (26.3%)	6	5/20 (25%)	10
Hyponatremia	10/14 (71.4%)	22	3/11 (27.3%)	8	11/19 (57.9%)	22	9/20 (45%)	24
Hypophosphatemia	4/14 (28.6%)	12	1/11 (9.1%)	1	8/19 (42.1%)	12	7/20 (35%)	12
Musculoskeletal and connective tissue disorders
Flank pain	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Chest wall pain	1/14 (7.1%)	1	1/11 (9.1%)	3	0/19 (0%)	0	0/20 (0%)	0
Musculoskeletal and connective tissue disorder - Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Myalgia	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Back pain	1/14 (7.1%)	1	4/11 (36.4%)	7	2/19 (10.5%)	2	6/20 (30%)	10
Musculoskeletal and connective tissue disorder - Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Musculoskeletal and connective tissue disorder - Other, specify	0/14 (0%)	0	2/11 (18.2%)	3	0/19 (0%)	0	0/20 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Nervous system disorders
Nervous system disorders - Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Vertigo	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Memory impairment	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Tremor	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Dizziness	2/14 (14.3%)	2	5/11 (45.5%)	7	2/19 (10.5%)	2	6/20 (30%)	7
Headache	1/14 (7.1%)	2	2/11 (18.2%)	3	1/19 (5.3%)	1	4/20 (20%)	4
Syncope	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Vasovagal reaction	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Psychiatric disorders
Delirium	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Anxiety	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Confusion	1/14 (7.1%)	1	2/11 (18.2%)	3	3/19 (15.8%)	3	3/20 (15%)	3
Psychiatric disorders - Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Depression	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Hallucinations	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Insomnia	2/14 (14.3%)	2	2/11 (18.2%)	3	2/19 (10.5%)	2	4/20 (20%)	4
Renal and urinary disorders
Urinary retention	1/14 (7.1%)	1	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Urinary incontinence	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Urinary tract pain	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Reproductive system and breast disorders
Genital edema	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/14 (14.3%)	3	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Pulmonary embolus	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	0/20 (0%)	0
Hiccups	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Sinusitis	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Epistaxis	1/14 (7.1%)	1	1/11 (9.1%)	1	1/19 (5.3%)	1	0/20 (0%)	0
Pleural effusion	0/14 (0%)	0	0/11 (0%)	0	3/19 (15.8%)	4	0/20 (0%)	0
Pneumothorax	1/14 (7.1%)	1	0/11 (0%)	0	2/19 (10.5%)	2	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, specify	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Allergic rhinitis	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	2/20 (10%)	2
Cough	1/14 (7.1%)	1	1/11 (9.1%)	2	3/19 (15.8%)	3	3/20 (15%)	4
Dyspnea	3/14 (21.4%)	4	2/11 (18.2%)	3	4/19 (21.1%)	5	6/20 (30%)	7
Hoarseness	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Nasal congestion	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Postnasal drip	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	1/20 (5%)	1
Sore throat	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Upper respiratory infection	1/14 (7.1%)	1	0/11 (0%)	0	0/19 (0%)	0	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Psoriasis	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Pruritus	2/14 (14.3%)	2	2/11 (18.2%)	2	3/19 (15.8%)	3	3/20 (15%)	3
Rash maculo-papular	0/14 (0%)	0	2/11 (18.2%)	2	1/19 (5.3%)	1	3/20 (15%)	3
Skin and subcutaneous tissue disorders - Other, specify	0/14 (0%)	0	0/11 (0%)	0	0/19 (0%)	0	4/20 (20%)	4
Skin ulceration	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	1/20 (5%)	1
Urticaria	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders - Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Skin and subcutaneous tissue disorders -Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	0/20 (0%)	0
Skin and subcutaneous tissue disorders -Other, specify	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	1/20 (5%)	1
Skin and subcutaneous tissue disorders -Other, specify	0/14 (0%)	0	1/11 (9.1%)	1	1/19 (5.3%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders -Other, mouth sore	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders -Other, Skin peeling - hand	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders -Other, specify	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders -Other, specify	0/14 (0%)	0	0/11 (0%)	0	1/19 (5.3%)	1	0/20 (0%)	0
Vascular disorders
Hypertension	0/14 (0%)	0	1/11 (9.1%)	1	0/19 (0%)	0	3/20 (15%)	3
Thromboembolic event	1/14 (7.1%)	1	1/11 (9.1%)	1	1/19 (5.3%)	1	2/20 (10%)	3
Hypotension	1/14 (7.1%)	2	0/11 (0%)	0	0/19 (0%)	0	3/20 (15%)	3

Limitations/Caveats

[Not Specified]

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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.