A Phase I Clinical Trial of Selinexor (KPT-330) in Combination With Temozolomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma
Phase: PHASE1
Conditions: Gliosarcoma, Newly Diagnosed, Glioblastoma
Sponsor: National Cancer Institute (NCI)

Abbreviated Title: Selinexor and Radiotherapy 
Version Date: 06/30/2025
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Abbreviated Title: Selinexor and Radiotherapy 
NIH Protocol #: 
20-C-0027 
Version Date: 
06/30/2025
NCT Number:  
NCT04216329
Title:  A Phase I Clinical Trial of Selinexor (KPT-330) in Combination with Temozolomide and 
Radiation Therapy in Patients with Newly Diagnosed Glioblastoma 
NCI Principal Investigator:
Kevin Camphausen, MD 
Radiation Oncology Branch (ROB)
Center for Cancer Research (CCR)
National Cancer Institute (NCI)
Bldg. 10, Rm B2-3500
9000 Rockville Pike
Bethesda, MD 20892
Phone:  240-760-6205
Email: camphauk@mail.nih.gov
  
Drug Name:
Selinexor (KPT-330)
Temozolomide
IND Number:
144383
144383
Sponsor:
CCR, NCI
CCR, NCI
Manufacturer:
KaryoPharm Therapeutics 
Inc.
Generic
Supplier:
KaryoPharm Therapeutics 
Inc.
NIH CC Pharmacy
Commercial Device: Radiation

Abbreviated Title: Selinexor and Radiotherapy 
Version Date: 06/30/2025
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PRÉCIS
Background:
•
Although radiation has been shown to improve outcomes in patients with glioblastoma 
(GBM), median survival remains poor. Even with the addition of temozolomide (TMZ) 
to surgical resection and radiotherapy, most GBMs will recur in field or adjacent to the 
high dose radiation volume. 
•
High rates of local failure indicate that GBM cells in situ are relatively radioresistant and 
that the effectiveness of GBM radiotherapy would benefit from additional 
radiosensitization.  
•
Selinexor has recently been shown to enhance the radiosensitivity of glioma cells both in 
vitro and in vivo.
Objectives:
•
Assess the safety, tolerability, and maximum tolerated dose of selinexor when combined 
with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma and 
gliosarcoma. 
Eligibility:
• Men and women greater than 18 years old
• Histologically confirmed newly diagnosed glioblastoma or gliosarcoma
• Karnofsky Performance Scale (KPS) ≥70
• Patients who have not previously been treated with chemotherapy or radiation therapy
Design:
•
This is a Phase I trial to determine the safety and tolerability of selinexor in combination 
with external beam radiation therapy (RT) and temozolomide in patients with newly 
diagnosed glioblastoma or gliosarcoma using a “3 plus 3 design,” and three dose 
escalation levels, with 3 patients per dose level (provided no DLT), a maximum of 21 
patients will be enrolled.
•
Patients will be treated with external beam radiation therapy in a standard manner with 
temozolomide given daily during radiation. Selinexor will be administered concurrent 
with the RT/temozolomide.
•
We anticipate accrual of 21 evaluable  patients which will take approximately 2 years. 
The accrual ceiling has been set to 24 patients.

Abbreviated Title: Selinexor and Radiotherapy 
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TABLE OF CONTENTS 
PRÉCIS............................................................................................................................................2
TABLE OF CONTENTS ................................................................................................................3
STATEMENT OF COMPLIANCE ................................................................................................8
1.
INTRODUCTION ...................................................................................................................9
1.1
Study Objectives ...............................................................................................................9
1.1.1
Primary Objective......................................................................................................9
1.1.2
Secondary Objective..................................................................................................9
1.1.3
Exploratory Objective................................................................................................9
1.2
Background and Rationale................................................................................................9
1.2.1
High Grade Glioma....................................................................................................9
1.2.2
XPO1 as a target for Glioma ...................................................................................10
1.2.3
Selinexor as an inhibitor of XPO1 (Pre-clinical).....................................................10
1.2.4
Selinexor as a radiosensitizer (Pre-clinical) ............................................................10
1.2.5
Selinexor with Chemotherapy (Pre-clinical) ...........................................................16
1.2.6
Selinexor with temozolomide..................................................................................17
1.2.7
Selinexor in Clinical Studies ...................................................................................18
1.2.8
Studies with Selinexor and Radiation......................................................................19
1.2.9
Updated Clinical and Efficacy Results (IB version 10, dated 9/21/2020)...............20
1.2.10
Rationale for Dose Level 2 and 3 Modification (amendment version date: 
03/26/2021)............................................................................................................................21
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT .......................................................21
2.1
Eligibility Criteria ...........................................................................................................21
2.1.1
Inclusion Criteria .....................................................................................................21
2.1.2
Exclusion Criteria ....................................................................................................22
2.1.3
Recruitment Strategies.............................................................................................23
2.2
Screening Evaluation ......................................................................................................23
2.2.1
Screening activities performed prior to obtaining informed consent ......................23
2.2.2
Screening activities performed after a consent for screening has been signed........23
2.3
Participant Registration and Status Update Procedures..................................................24
2.3.1
Treatment Assignment Procedures..........................................................................24
2.4
Baseline Evaluation.........................................................................................................24
3
STUDY IMPLEMENTATION .............................................................................................25

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3.1
Study Design...................................................................................................................25
3.1.1
Concurrent Therapy.................................................................................................25
3.1.2
Adjuvant Therapy ....................................................................................................25
3.1.3
Study Schema ..........................................................................................................26
3.1.4
Dose Limiting Toxicity............................................................................................26
3.1.5
Dose Escalation .......................................................................................................26
3.1.6
Study Stopping Rule................................................................................................28
3.2
Drug Administration .......................................................................................................28
3.2.1
Selinexor..................................................................................................................28
3.2.2
Temozolomide .........................................................................................................28
3.3
Dose Modifications.........................................................................................................28
3.3.1
Radiation Therapy ...................................................................................................28
3.3.2
Concurrent Systemic Agents ...................................................................................29
3.4
Questionnaires (For English Speaking Patients Only)....................................................33
3.5
Study Calendar................................................................................................................35
3.6
Radiation Therapy Guidelines ........................................................................................37
3.6.1
Scheduling ...............................................................................................................37
3.6.2
Technique ................................................................................................................37
3.6.3
Target coverage and dose limits ..............................................................................37
3.6.4
Critical structures.....................................................................................................37
3.7
Cost and Compensation ..................................................................................................38
3.7.1
Costs ........................................................................................................................38
3.7.2
Compensation ..........................................................................................................38
3.7.3
Reimbursement........................................................................................................38
3.8
Criteria for Removal from Protocol Therapy and Off Study Criteria.............................38
3.8.1
Criteria for removal from protocol therapy .............................................................38
3.8.2
Off-Study Criteria....................................................................................................39
3.8.3
Lost to Follow-up ....................................................................................................39
4
CONCOMITANT MEDICATIONS/MEASURES...............................................................39
5
CORRELATIVE STUDIES FOR RESEARCH ...................................................................40
6
DATA COLLECTION AND EVALUATION .....................................................................40
6.1
Data Collection ...............................................................................................................40
6.2
Data Sharing Plans..........................................................................................................41

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6.2.1
Human Data Sharing Plan .......................................................................................41
6.2.2
Genomic Data Sharing Plan.....................................................................................41
6.3
Response Criteria ............................................................................................................41
6.3.1
Modified RANO Response Criteria.........................................................................41
6.4
Toxicity Criteria..............................................................................................................43
7
NIH REPORTING REQUIREMENTS/DATA SAFETY MONITORING PLAN ..............44
7.1
Definitions.......................................................................................................................44
7.2
OHSRP Office of Compliance and Training / IRB Reporting........................................44
7.2.1
Expedited Reporting ................................................................................................44
7.2.2
IRB Requirements for PI Reporting at Continuing Review ....................................44
7.3
NCI Clinical Director Reporting.....................................................................................44
7.4
NIH Required Data and Safety Monitoring Plan............................................................44
7.4.1
Principal Investigator/Research Team.....................................................................44
8
SPONSOR PROTOCOL/SAFETY REPORTING................................................................45
8.1
Definitions.......................................................................................................................45
8.1.1
Adverse Event..........................................................................................................45
8.1.2
Treatment-emergent adverse event (TEAE)............................................................45
8.1.3
Serious Adverse Event (SAE) .................................................................................45
8.1.4
Life-threatening .......................................................................................................46
8.1.5
Severity....................................................................................................................46
8.1.6
Relationship to Study Product .................................................................................46
8.2
Assessment of Safety Events ..........................................................................................46
8.3
Reporting of Serious Adverse Events .............................................................................47
8.4
Waiver of Expedited Reporting to CCR .........................................................................47
8.5
Safety Reporting Criteria to the Pharmaceutical Collaborators......................................47
8.6
Reporting Pregnancy.......................................................................................................47
8.6.1
Maternal exposure ..................................................................................................47
8.6.2
Paternal exposure.....................................................................................................47
8.7
Regulatory Reporting for Studies Conducted Under CCR Sponsored IND ...................48
8.8
Sponsor Deviation Reporting..........................................................................................48
9
CLINICAL MONITORING..................................................................................................48
10
STATISTICAL CONSIDERATIONS ...............................................................................49
10.1
Statistical Hypothesis......................................................................................................49

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10.1.1
Primary Endpoint.....................................................................................................49
10.1.2
Secondary Endpoint.................................................................................................49
10.2
Sample Size Determination.............................................................................................49
10.3
Populations for Analyses ................................................................................................50
10.3.1
Evaluable for toxicity ..............................................................................................50
10.3.2
Evaluable for response.............................................................................................50
10.4
Statistical Analyses .........................................................................................................50
10.4.1
General Approach....................................................................................................50
10.4.2
Analysis of the Primary Endpoints..........................................................................50
10.4.3
Analysis of the Secondary and Exploratory Endpoint(s) ........................................50
10.4.4
Safety Analyses .......................................................................................................51
10.4.5
Planned Interim Analyses........................................................................................51
10.4.6
Sub-Group Analyses................................................................................................51
10.4.7
Tabulation of Individual Participant Data ...............................................................51
10.4.8
Exploratory Analyses...............................................................................................51
11
COLLABORATIVE AGREEMENTS...............................................................................51
11.1
Clinical Trial Agreement (CTA).....................................................................................51
12
HUMAN SUBJECTS PROTECTIONS.............................................................................51
12.1
Rationale For Subject Selection......................................................................................51
12.2
Participation of Children.................................................................................................52
12.3
Participation of Subjects Unable to Give Consent..........................................................52
12.4
Risk/Benefit Assessment.................................................................................................52
12.4.1
Known Potential Risks ............................................................................................52
12.4.2
Known Potential Benefits........................................................................................53
12.4.3
Assessment of Potential Risks and Benefits............................................................53
12.5
Consent Process and Documentation..............................................................................53
12.5.1
Consent Process for Adults Who Lack Capacity to Consent to Research 
Participation...........................................................................................................................54
13
REGULATORY AND OPERATIONAL CONSIDERATIONS.......................................54
13.1
Study Discontinuation and Closure.................................................................................54
13.2
Quality Assurance and Quality Control..........................................................................55
13.3
Conflict of Interest Policy...............................................................................................55
13.4
Confidentiality and Privacy ............................................................................................55

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14
PHARMACEUTICAL AND DEVICE INFORMATION .................................................56
14.1
Selinexor (KPT-330) (IND # 144383)............................................................................56
14.1.1
Source/Acquisition and Accountability...................................................................56
14.1.2
Toxicity....................................................................................................................56
14.1.3
Formulation and preparation....................................................................................59
14.1.4
Stability and Storage................................................................................................59
14.1.5
Administration procedures.......................................................................................59
14.1.6
Incompatibilities: None known................................................................................60
14.2
Temozolomide (IND # 144383)......................................................................................60
14.2.1
Source ......................................................................................................................60
14.2.2
Administration procedures.......................................................................................60
14.3
Radiation .........................................................................................................................60
14.3.1
Source ......................................................................................................................60
14.3.2
Toxicity to brain ......................................................................................................60
14.3.3
Administration Procedures ......................................................................................61
15
REFERENCES ...................................................................................................................62
16
APPENDICES ....................................................................................................................65
16.1
Appendix A: Performance Status Criteria ......................................................................65
16.2
Appendix B: RTOG Radiation Morbidity Scoring Criteria............................................66
16.3
Appendix C: RTOG Late Radiation Morbidity Scoring Criteria....................................67
16.4
Appendix D: MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT).......68
16.5
Appendix E:  Neuro-QOL Item Bank v2.0.....................................................................70
16.6
Appendix F: Emotional Distress -Depression-Short Form 8a ........................................71
16.7
Appendix G: PRO-CTCAE.............................................................................................73
16.8
Appendix H: Oral medication diary For selinexor – Weekly .........................................76
16.9
Appendix I: Oral medication diary For selinexor – Twice weekly.................................77

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STATEMENT OF COMPLIANCE
The trial will be carried out in accordance with International Council for Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.

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1. INTRODUCTION
1.1
STUDY OBJECTIVES
1.1.1
Primary Objective
Assess the safety, tolerability, and maximum tolerated dose of selinexor when combined with 
temozolomide and radiotherapy in patients with newly diagnosed glioblastoma and gliosarcoma. 
1.1.2
Secondary Objective
Define dose-limiting toxicities including effects on QOL and neurocognition of selinexor when 
combined with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma 
and gliosarcoma.
1.1.3
Exploratory Objective
Determine the progression free survival and overall survival of patients with glioblastoma and 
gliosarcoma treated with temozolomide, radiation and selinexor.
1.2
BACKGROUND AND RATIONALE
1.2.1
High Grade Glioma
Although advances in surgical management and radiation therapy have improved survival for 
patients with glioblastoma, life expectancy remains poor. Median survival for patients with 
newly diagnosed glioblastoma is 16.1 months  [1]. Most failures occur in the high-dose 
radiotherapy (RT) field [2]. This high rate of recurrence of GBM has highlighted the importance 
of optimizing local therapies, which include both surgical and radiation interventions. Multiple 
studies have shown a correlation between the extent of tumor resection and survival [3], [4]. 
Prospective, randomized trials from the Scandinavian Glioblastoma Study Group (SGSG) and 
the Brain Tumor Study Group have also shown a survival benefit with the addition of post-
operative radiation [5], [6]. In the SGSG trial median survival increased from 5.2 months with 
supportive care alone to 10.8 months with the addition of post-operative radiation [6]. Attempts 
to improve local control with radiation have included altered fractionation schemes [7]; dose 
escalation with boost, stereotactic radiotherapy [8], and brachytherapy [9]. Unfortunately, these 
techniques have added minimal therapeutic benefit. Many of these techniques can lead to an 
increased incidence of necrosis and higher rates of re-operation with little or no survival 
advantage. This high rate of recurrence of GBM has highlighted the importance of optimizing 
local therapies, which include both surgical and radiation interventions. 
The Stupp trial [11] represents the only significant improvement in outcomes for upfront GBM 
treatment in more than a decade and established the addition of  temozolomide to resection and 
radiation as the standard of care. The trial’s 5-year outcome with temozolomide demonstrated an 
improved overall survival (9.8% vs 1.9% with RT alone) as well as improved median survival 
(14.6 months vs 12.1 months with RT alone). However, in this trial temozolomide was added 
both concurrently with the RT and adjuvantly after the RT/temozolomide. Thus, it cannot be 
determined how much each phase of temozolomide contributed to the improved outcome or if 
temozolomide acts as a radiosensitizer. 

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1.2.2
XPO1 as a target for Glioma
In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through 
the nuclear pore complex (NPC). Exportin 1 (XPO1) is the major export receptor implicated in 
one of the two distinct RNA export pathways across the NPC [12]. This pathway is responsible 
for exporting ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs) and a certain subset of 
messenger RNAs (mRNAs) [13], [14]. Additionally, XPO1 is the sole nuclear exporter of many 
tumor suppressor proteins, including p53 and p27, and is overexpressed in many cancers [15]. In 
a study of XPO1 expression in gliomas, high XPO1 expression was shown to be correlated with 
poor patient survival and was dramatically increased in GBM compared to lower grade tumors 
[16]. As such, XPO1 has become a protein of interest for targeting in treatment of high grade 
gliomas.
1.2.3
Selinexor as an inhibitor of XPO1 (Pre-clinical)
Selinexor (KPT-330) is a small molecule selective inhibitor of nuclear export (SINE) which 
binds to the cargo-binding portion of the XPO1 protein to prevent protein transport from the 
nucleus to the cytoplasm. In preclinical cancer models it has demonstrated antitumoral activity 
[17], [18], [19]. In the first preclinical trial that tested its efficacy against GBM cell lines, 
Selinexor demonstrated anti-tumor efficacy in both in vitro and in vivo models.  The authors 
reported there was no suggestion of overt neurotoxicity, and penetration of the blood-brain 
barrier was excellent [15].  The suggested mechanism of action was through induction of 
apoptosis likely secondary to effects on both protein and mRNA export inhibition.
1.2.4
Selinexor as a radiosensitizer (Pre-clinical)
Work in our lab has shown that Selinexor enhances the radiosensitivity of glioblastoma stem-like 
cell (GSC) lines, NSC11 and 0923, and U251 (glioblastoma) cells in both in vitro and in vivo 
conditions [20]. As shown in Figure 1 these three cell lines are sensitized to irradiation by pre-
treatment with Selinexor for 1hr pre-irradiation.  The dose enhancement factor (DEF) at a 
surviving fraction of 0.1 for NSC11 was 1.46, for 0923 was 1.39, and for U251 was 1.63.  The 
plating efficiency of each cell line was 0.25, 0.68 and 0.27 with drug alone, respectively.  These 
DEFs represent significant radiosensitization and show an enhancement in both GSCs and long-
established cell lines. 

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.
Figure 1: Effect of Selinexor on the in vitro radiosensitivity of GBM cells. A) NSC11 B) 
0923 and C) U251 cells. Selinexor (1M) or vehicle (DMSO) were added to culture 
media 1h before irradiation; 24h later media was replaced with fresh, drug-free media 
and colonies determined after 10-14 days. Dose enhancement factors (DEFs) were 
calculated at a surviving fraction of 0.1 or for U251 at 0.15. Values represent the mean ± 
SEM of 3 independent experiments. * p  < 0.05, Student's t-test (Selinexor vs. Vehicle)
In a separate study investigating colorectal tumor cells also showed that Selinexor enhanced in 
vitro radiosensitivity.  In that study, the proposed mechanism of radiosensitivity was prevention 
of surviving export into the cytoplasm resulting in increased in radiation-induced apoptosis [21].  
However, in our investigations no increase in apoptosis was observed suggesting a separate 
mechanism of radiosensitivity (Figure 2).

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Figure 2: Effect of Selinexor on radiation-induced apoptosis. Selinexor (l µM) or vehicle 
was added to NSCII (left) or 0923 (right) cultures lh prior to irradiation (5Gy) and cells 
collected for analysis 24h later. Cells undergoing apoptosis were quantified according to 
annexin V staining (Annexin V Apoptosis Detection Kit, BD Biosciences). Briefly, cells 
werc resuspended in 1xAnnexin V Binding Buffer and incubated with Annexin V•Cy5 
antibody in the dark at room temperature for each treatment condition 1--Hoechst 33258 
was added for live/dead and samples were analyzed by flow cytometry (BD LSR 
Fortessa). Data presented are the mean SEM Of 3 independent experiments. 
In addition to the export of a variety of proteins, XPO1 mediates the nuclear export of rRNA, 
suggesting that XPO1 inhibition may lead to a reduction in gene translation.  Consistent with this 
hypothesis, Tabe et al. reported that in lymphoma cell lines the XPO1 inhibitor KPT185 reduced 
the nuclear export of 50 ribosomal proteins suggesting an inhibition of ribosomal biogenesis 
[22]. As an initial estimation of gene translation, the ratio of polysome-bound RNA to 
monosome-bound RNA (translational efficiency, TE) was determined from polysome profiles 
generated from NSC11 and 0923 GSCs as a function of time after addition of Selinexor to the 
culture media (Figure 3). Representative profiles show a reduction in the polysome fraction in 
both GSC lines beginning 1h after Selinexor treatment corresponding to a significant decrease in 
TE at 1h, which was further reduced after 24h of drug exposure. These results suggest that 
Selinexor disrupts gene translation.  Decreased translational efficiency as well as the reduction in 
the polysome profile in GBM cells after Selinexor treatment, suggest reduction in translation 
may play a role in XPO1 inhibited radiosensitization, possibly due to reduction in ribosome 
biogenesis (Figure 3). Following the same protocol on normal lung fibroblast cell lines MRC5 
and MRC9 Selinexor had no effect on the radiosensitivity of these normal lines.

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Figure 3: Translational efficiency and protein synthesis in GBM cells treated with 
Selinexor. Representative polysome profiles of NSC Il (top) and 0923 (bottom) cells as a 
function of time after Selinexor (1µmol/L) addition to media. Translational efficiency 
(TE) values represent the mean ± SEM of 3 independent experiments. *p≤0.05 Student's 
t-test for Selinexor v. Vehicle
To evaluate the potential of Selinexor to enhance GBM radiosensitivity under in vivo conditions, 
we used orthotopic xenografts initiated from NSC11 cells.  In vitro results suggested that protein 
synthesis provides a marker of Selinexor radiosensitizing activity. Whereas it is not possible to 
directly measure protein synthesis in brain tumors, polysome profiles can be generated and 
translational efficiency (TE) determined.  Towards this end, mice bearing NSC11 brain tumors 
(40 days post-implantation) were treated with a single dose of Selinexor (20mg/kg); tumors were 
collected at times out to 48h and polysome profiles generated from individual tumors.  
Representative profiles are shown in Figure 4 with the listed TEs (mean ± SEM) generated from 
3 mice.  As reflected by the reduction in polysome fraction, TE was decreased by 1h after 
Selinexor administration reaching a maximum reduction by approximately 24h, which appeared 
to begin to recover towards untreated levels at 48h.  These results indicate that Selinexor 
penetrates the blood-brain barrier and suggests that it targets the same processes within the tumor 
as detected in vitro.  

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Figure 4: The effect of Selinexor on translational efficiency and of NSC11-initiated 
orthotopic xenograft. Mice bearing orthotopic xenografts were treated with vehicle or 
Selinexor (20mg/kg) by oral gavage. Tumors were collected at the indicated timepoints 
and polysome profiles generated. Representative profiles from each treatment group are 
shown; Translational efficiency (TE) values represent the mean ± SEM of 3 mice. 
Student's t-test, * p≤0.05, Selinexor v. Vehicle. 
To test the antitumor effectiveness of the Selinexor/radiation combination, 24 days after 
intracerebral implant, mice were randomized according to BLI signal into 4 groups: vehicle 
(control), radiation (2Gy), Selinexor (20 mg/kg), and Selinexor plus radiation.  Radiation was 
delivered daily for 5 days (5x2Gy) with Selinexor delivered on days 1, 3, and 5, 1h prior to local 
irradiation.  Mice were followed until the initial onset of morbidity and survival curves 
generated.  Selinexor treatment of mice alone had no significant effect on survival as compared 
to vehicle; radiation alone resulted in a significant increase in survival (Figure 5). The survival 
of mice receiving the combination protocol was significantly increased as compared with control 
and, importantly, as compared with radiation alone (p<0.004).  The median survival times for the 
treatment groups are shown in the boxplots in Figure 5. Whereas the median survival after 
Selinexor was not significantly different from vehicle, radiation alone increased median survival 
by 9 days and the combination by 18 days versus vehicle, indicating that the combination 
protocol increased tumor radiosensitivity with an apparent DEF of 2. Thus, these data suggest 
that Selinexor inhibits gene translation in orthotopic brain tumors and enhances their 
radiosensitivity.

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Figure 5: The effect of Selinexor on radioresponse of NSC11-initiated orthotopic 
xenograft. At 24 days after orthotopic implant, mice were randomized and treatment 
initiated the following day as  described in text (IR= 5x2Gy). Kaplan—Meier survival 
curves were generated with log-rank analysis for comparison. Box plot graph of median 
survival of each treatment group, * p < 0.05, by Dunnett's multiple comparison test.
To test whether Selinexor was specific for tumor cells compared to normal cells, protein 
synthesis after selinexor treatment was compared between NSC11 and 923 and three normal cell 
lines MRC5, MRC9 and astrocytes.  As shown in Figure 6 at each time point measured (1-24h) 
there was a reduction of protein synthesis in the tumor cells which was not measured in any of 
the three normal cell lines.  This is consistent with selinexor having a tumor specific mechanism 
of action. 
Figure 6: Protein synthesis 
measured as a function of time 
after selinexor (umol/L) addition 
to media.  Cyclohexamide (CHX, 
0.25umol/L, 4h) was used as a 
positive control for protein 
synthesis inhibition. 

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1.2.5
Selinexor with Chemotherapy (Pre-clinical)
Nu/nu mice engrafted with the breast cancer MDA-MB-231 cells were treated with vehicle, 
Selinexor, cisplatin, docetaxel, or Selinexor plus either of the chemotherapy drugs. The mean 
tumor volume for the vehicle control group (Group 1) increased from 172 mm3 on day 1 to 665 
mm3 (287%) on day 25. Mice treated with 2.5 mg/kg Selinexor, 4 mg/kg cisplatin, and 4 mg/kg 
docetaxel alone showed a 68% (p < 0.05), 28% (not significant) or 53% (p < 0.05) tumor growth 
inhibition (TGI), respectively, when compared to vehicle control. Sequential treatment of 4 
mg/kg docetaxel followed by 2.5 mg/kg Selinexor or 4 mg/kg cisplatin followed by Selinexor 
resulted in 93.9% (p < 0.001) TGI and 103.4% (p < 0.001) TGI (9.6% tumor regression), 
respectively, after 25 days (Figure 7A). Selinexor treatment alone or in combination with 
chemotherapy initially resulted in animal weight loss; however, all groups recovered and there 
were no statistically significant differences in body weight among the treatment groups at the end 
of the study, as shown in (Figure 7B). Significant weight loss has not been seen in the clinical 
trials to date. The expression of DNA damage response (DDR) proteins was examined using 
immunoblots in tumors from vehicle, Selinexor, cisplatin, and docetaxel-treated animals. 
Selinexor, even at 2.5 mg/kg, lowered DDR protein expression, while cisplatin and docetaxel 
had no effect on the steady-state levels of the DDR proteins (Figure 7C).

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Figure 7: Selinexor demonstrates synergistic anti-tumor effects in combination with cisplatin or 
docetaxel and inhibits the expression of DDR proteins in an in vivo breast cancer model: Nu/nu 
mice were allocated to six groups of 4 mice and treated with vehicle (1), 2.5 mg/kg Selinexor (2), 
4 mg/kg cisplatin (3), 4 mg/kg docetaxel (4), Selinexor in combination with cisplatin (5) or 
docetaxel (6) for 25 days. For groups V and Vi, Selinexor was administered 6 hours after treatment 
with cisplatin and docetaxel respectively. Selinexor was administered orally, whereas cisplatin and 
docetaxel were administered by intraperitoneal injection. (A) Mean tumor volumes were calculated 
from the length and width measurements. Group means were calculated and are shown with error 
bars representing standard error of the mean (SEM) for each group. Combinatory treatments 
inhibited tumor growth better than each single agent. (B) The percent daily weight changes for 
each animal and the means for each treatment group were calculated. Error bars represent the 
SEM. There was no significant weight change among the groups at the end of the study. (C) At the 
end of the in vivo xenograft study (day 25), excised tumors from the vehicle Selinexor, cisplatin and 
docetaxel treated groups were assayed either by immunoblots for the expression of DDR proteins. 
Selinexor, but not cisplatin or docetaxel, reduced the levels of DDR proteins: CHEK1, MLH1, 
MSH2, PMS2, Rad51.
1.2.6
Selinexor with temozolomide
Selinexor and TMZ were tested in vitro using both clonogenic survival and gamma-H2AX (a 
marker of DNA-DS breaks) assays.  U251 cells were cultured in 6-well plates and temozolomide 
(25µM), selinexor (0.5µM) or both were added to the culture media 1hr prior to the delivery of 
2Gy irradiation. A lower dose of Selinexor was used as the triple combination was more toxic.  
Colonies were counted 10-14 days later and as shown in Figure 8A, the triple combination had 
more cell kill than either of the individual drugs in combination with irradiation.  The 
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combination had a greater dose enhancement of 1.26. Similarly, the gamma-H2AX assay showed 
the greatest number of foci at 24h in the triple combination group (Figure 8B). These data 
suggest that the triple combination of Selinexor and temozolomide/RT should have a greater cell 
killing effect than any of the two agent combinations.
Figure 8: Influence of TMZ (25 µM), KPT330 (0.5 µM) and their combination on A) clonogenic 
cell survival in U251 cells and B) gamma-H2AX foci repair. A) Cells were exposed to treatments 
for 1 h before irradiation. 24 h after irradiation the drug containing media was removed and 
cells were fed fresh, drug-free media. Colonies were counted 10-14 days thereafter and the dose 
enhancement factor (DEF) for each group was calculated at a surviving fraction (SF) of 0.1. The 
DEFs for TMZ, KPT330, and combination treatments were 0.94, 1.06, and 1.26 respectively. 
Values are represented as the mean ± SEM of 3 independent experiments. B) Cells were exposed 
to treatments for 1 h, irradiated with 2 Gy, and collected at the indicated timepoints to evaluate 
DNA repair. Foci were evaluated in 50 nuclei per treatment per experiment. (* p<0.05; ** 
p<0.01, *** p<0.001; ****p<0.0001)
1.2.7
Selinexor in Clinical Studies
1.2.7.1
Phase I Studies:
1.2.7.1.1 PK of Selinexor in Phase 1 Studies KCP-330-001 and KCP-330-002 
Plasma Selinexor PK parameters were determined following oral administration of Selinexor in 
patients with hematologic and solid malignancies (KCP-330-001 and KCP-330-002). Based on 
unaudited results, Selinexor exhibited dose-proportional PK and moderate- to moderately-high 
inter-patient variability following repeated oral dosing in 8-to-10 dose/28-day cycle dose 
regimens over a dose range of 3 to 65 mg/m2 (0.08 to 1.76 mg/kg). The median time to peak 
plasma levels (tmax) of Selinexor was ~2 to 4 hours after administration. The apparent volume of 
distribution after non-intravenous administration (Vd/F) was 1.5 to 2.5 L/kg, indicating good 
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dose-independent, and similar across patients with different tumors. Sex or age did not appear to 
affect Selinexor PK. As a part of Study KCP-330-002, 8 patients were given 20, 28, or 39 mg/m2 
Selinexor along with 500 or 1000 mg of acetaminophen; there were no clinically significant 
laboratory abnormalities or symptoms associated with the co-administration. Preliminary 
unaudited PK analysis was conducted, and the results indicated there was no difference in 
Selinexor plasma exposure in these patients when compared with equivalently-dosed patients 
with Selinexor alone. Given the theoretical potential for GSH depletion, the total dose of 
acetaminophen should be ≤1 gram per day on days of Selinexor dosing. 
1.2.7.2
PK Rationale for Flat Dosing Regimen: Studies KCP-330-001 and KCP-330-002 
PK analyses support the use of fixed, rather than body surface area (BSA)-based, dosing for 
Selinexor. The 5th and 95th percentile for BSA values (n = 331 patients) in the Phase 1 Studies 
KCP-330-001 and KCP-330-002 are 1.5 and 2.3 m2, respectively. PK values (Cmax and AUC0-∞) 
for Selinexor doses 3 to 85 mg/m2 BSA (females) and 12 to 85 mg/m2 BSA (males) were similar 
across this typical BSA range, indicating that exposure is not strongly correlated with BSA and 
justifying the use of fixed milligram doses for Selinexor in the clinic.
1.2.7.3
Phase II Studies:
KCP-330-004: (KING: KPT-330 in Glioblastoma): A Phase 2 Study Evaluating the Efficacy and 
Safety of Selinexor (KPT-330) in Patients with Recurrent Gliomas 
1.2.7.3.1 KCP-330-004 Study Design 
This is a multicenter, Phase 2, open-label study to evaluate the safety and efficacy of Selinexor in 
approximately 57 patients with recurrent WHO Grade 4 glioma (glioblastoma, glioblastoma 
multiforme [GBM], and subvariants) (NCT01986348). Patients in Arms A and B receive 
Selinexor 50 mg/m2 (80-90mg/dose) for 4 weeks per 4-week cycle. Patients in Surgical Arm A 
receive an additional 3 doses of Selinexor prior to surgery and resume Selinexor after recovery. 
Patients in Arm C receive Selinexor 60 mg bi-weekly (BIW) and patients in Arm D receive 80 
mg weekly for 4 weeks per 4-week cycle. Primary end point was 6-months PFS rate. 
This study has been re-activated to add 12 patients. Study enrollment will close when 75 patients 
are enrolled.
1.2.7.3.2 KCP-330-004 Efficacy Results 
Selinexor had reasonable brain penetration as shown by significant intra-tumoral selinexor 
concentrations in surgical specimens (Arm A) [23]. The average tumor concentration was 
136nM compared to a plasma concentration of 836nM for a tumor/plasma ratio of 0.14 (N=6).  
In the most recent efficacy analysis, the overall response rate (ORR) was 13% in Arm B, 0% in 
Arm C, and 8 % in Arm D [24]. The 6 months PFS rate was 17% in Arm B, 8% in Arm C, and 
~20% in Arm D [24]. The toxicity profile for Arm B 50mg/m2 (80-90mg/dose) twice a week was 
high and thus two additional arms C and D were added with bi-weekly dosing of 60mg for Arm 
C, and once weekly dosing of 80mg for Arm D.  Arm C (60mg BIW) had one grade 3 DLT of 
fatigue and Arm D (80mg QW) had one grade 3 DLT of lymphopenia.  No grade 4 or 5 DLT 
were seen with the once weekly dosing schedule.  
1.2.8
Studies with Selinexor and Radiation
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1.2.9
Updated Clinical and Efficacy Results (IB version 10, dated 9/21/2020)
Results from ongoing and completed clinical studies have shown that selinexor induces durable 
antitumor responses across a broad range of relapsed or refractory (RR) hematologic and solid 
tumor cancers, which is consistent with its proposed mechanism of action. In general, these 
effects appear to be independent of tumor type or prior treatment(s). 
As of 31 March 2020, 3419 patients with hematologic or solid-tumor malignancies had received 
at least 1 dose of selinexor; in addition, 301 patients received at least 1 dose of selinexor or 
blinded study treatment (i.e., selinexor or placebo) for a total of 3720 patients. These 3720 
patients include 2310 patients from Company-sponsored trials (CSTs; 2009 who received 
selinexor and 301 who received blinded study treatment), 1201 active patients from Investigator-
Sponsored Trials (ISTs) who received selinexor, and 161 patients from the selinexor Expanded 
Access Program (EAP) who received selinexor; and 9 and 39 patients who received selinexor 
through clinical trials sponsored by Ono Pharmaceutical Co., Ltd and Antengene, respectively. 
The most commonly reported treatment-emergent adverse events (TEAEs) for selinexor in CSTs 
were nausea (66.1%), fatigue (56.7%), anorexia (includes MedDRA “decreased appetite”; 
51.1%), thrombocytopenia (51.0%), anemia (43.5%), vomiting (38.7%), and diarrhea (36.6%), 
that were generally low-grade and reversible. The TEAEs of thrombocytopenia and anemia, 
which can be higher grade, were reported primarily in patients with hematologic malignancies. 
1.2.9.1
KCP330012/STORM
Based on activity observed for selinexor in combination with dexamethasone in RRMM in Part 2 
of the Study KCP330012/STORM (hereafter referred to as STORM), selinexor received 
accelerated US Food and Drug Administration (FDA) approval in July 2019 for the treatment of 
adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior 
therapies and whose disease is refractory to at least 2 PIs, at least 2 immunomodulatory agents, 
and an anti-CD38 monoclonal antibody. The objective response rate (ORR) was 26.2%, with a 
quick median time to first response of 4.1 weeks (range: 1 to 14 weeks). The median 
progression-free survival (PFS) was 3.7 months and median overall survival (OS) was 8.4 
months.
1.2.9.2
KCP330-023/ BOSTON
Study KCP330-023/ BOSTON (hereafter referred to as BOSTON) evaluating selinexor plus 
bortezomib plus lowdose dexamethasone (SVd) vs bortezomib and dexamethasone alone (Vd) in 
RRMM in which the SVd arm showed a clinically and statistically significant improvement for 
PFS compared to the Vd arm (median PFS 13.93 months vs 9.46 months) serves as a 
confirmatory study of the accelerated approval asserting that the responses observed in the 
STORM study are highly likely to confer clinical benefit. A supplemental new drug application 
(sNDA) was submitted to the FDA in May 2020 seeking full approval for selinexor as a 
treatment for patients with MM after at least 1 prior line of therapy. 
1.2.9.3
KCP-330-009/SADAL
Selinexor has shown activity in diffuse large B-cell lymphoma (DLBCL) in Study KCP-330-
009/SADAL (hereafter referred to as SADAL), a multi-center, single-arm Phase 2b study. Based 
on the results of this study, selinexor received approval from FDA in June 2020 for the treatment 
of adult patients with RR DLBCL, not otherwise specified, including DLBCL arising from 

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follicular lymphoma, after at least 2 lines of systemic therapy. In this study, the ORR was 28.3%, 
median duration of response (DOR) was 9.3 months and median OS was 9.1 months. 
Study XPORT-DLBCL-030 was agreed as the confirmatory trial for evaluating selinexor in 
DLBCL. This trial will assess the effect of selinexor or placebo added to a standard backbone 
immunochemotherapy of rituximab-gemcitabine-dexamethasone-platinum (R-GDP) in patients 
with 1 to 3 prior treatments for DLBCL. 
1.2.10 Rationale for Dose Level 2 and 3 Modification (amendment version date: 
03/26/2021)
We are using Selinexor as a radiation sensitizer.  In theory, it would be more effective if we gave 
it more frequently as radiation is given 5-days per week.  However, we did not have sufficient 
clinical data to support multi-dosing per week when the trial was originally written. We now 
have that data and are thus requesting the change. The once-a-week dosing was supported by the 
FDA approval of Selinexor in the treatment of multiple myeloma (80mg weekly). The new data 
supporting the twice a week dosing (BIW) is from ARM C of the recently reported KING trial 
[23].  The KING trial is a Phase 2 study of Selinexor monotherapy in recurrent glioblastoma 
multiforme. In that trial 14 patients were treated with 60mg BIW with a similar side effect 
profile to the 80mg once per week given in ARM D. Additionally, in the pre-surgical ARM A of 
the KING study 6 patients were dosed with 50mg/m2, 2-3 hours prior to surgical resection.  
136nM of Selinexor was measured within the tumor and is consistent with the desired CNS dose 
in animal models. Thus, 60mg BIW should give adequate penetration of the CNS, allowing 
additional fractions of radiation to be sensitized with an equivalent side effect profile. The 
company has additional unpublished data from a trial in patients with lymphoma with twice 
weekly dosing (60mg BIW) which has recently received FDA approval.
Thus, we  havechanged dose levels 2 and 3 in our trial from once-a-week dosing to twice a week 
dosing.
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT 
2.1
ELIGIBILITY CRITERIA
2.1.1
Inclusion Criteria
2.1.1.1
Histological diagnosis
•
Pathologically confirmed glioblastoma or gliosarcoma (including astrocytoma, 
grade IV)
2.1.1.2
Patients must be eligible for definitive external beam radiotherapy and temozolomide.
2.1.1.3
Age >18 years. Because no dosing or adverse event data are currently available on the 
use of Selinexor in combination with temozolomide in patients <18 years of age, 
children are excluded from this study.
2.1.1.4
Patients should have a KPS greater than or equal to 70 (see Appendix A).
2.1.1.5
Absolute neutrophil count (ANC) >1.5x109/L; platelet count >100x109/L; and 
hemoglobin (Hb) >9.0 g/dL. Note: the use of transfusion or other intervention prior to 
cycle 1 day 1 to achieve Hb >9.0 g/dL is acceptable.
2.1.1.6
Ability of subject or Legally Authorized Representative (LAR) to understand and the 
willingness to sign a written informed consent document.

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2.1.1.7
The effects of Selinexor on the developing human fetus are unknown. For this reason 
and because Selinexor agents as well as other therapeutic agents used in this trial are 
known to be teratogenic, women of child-bearing potential and men must agree to use 
adequate contraception (hormonal or barrier method of birth control; abstinence) prior 
to study entry, for the duration of study treatment and for one month after 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.
2.1.1.8
Patients must have had surgery and/or biopsy not greater than 8 weeks prior to initial 
evaluation to be eligible for this study.
2.1.2
Exclusion Criteria
2.1.2.1
Patients who are receiving any other investigational agents and have had prior therapy 
including:
•
Patents who have previously received radiation therapy (RT) to the brain.
•
Patients who received chemotherapy for the treatment of their glioma 
•
Patients who are being treated with implanted gliadel wafers 
•
Patients who are being treated with tumor treating fields
2.1.2.2
History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to selinexor or temozolomide used in study.
2.1.2.3
Patients with coagulation problems and medically significant bleeding in the month 
prior to start of treatment (peptic ulcers, epistaxis, spontaneous bleeding). Prior history 
of DVT or PE is not exclusionary
2.1.2.4
Patients with active uncontrolled or suspected infections
2.1.2.5
Patients with severe liver dysfunction defined as: 
•
Total bilirubin > 1.5 x upper limit of normal (ULN) Note: Subjects with Gilberts 
syndrome should not be excluded as long as total bilirubin is < 3.0 x ULN and 
documentation to support diagnosis is available.
•
Serum glutamate pyruvate transaminase (SGPT) or called as Alanine 
aminotransferase (ALT) ≥3 x ULN = 135 U/L; for the purpose of this study, the 
ULN for SGPT is 45 U/L
•
Serum glutamic oxaloacetic transaminase (SGOT) or called as Aspartate 
aminotransferase (AST) ≥3 x ULN = 150 U/L; for the purpose of this study, the 
ULN for SGOT is 50 U/L
•
Serum albumin > 2 x ULN
2.1.2.6
Known active hepatitis A, B, or C infection
2.1.2.7
HIV patients are not eligible because of their immunocompromised status and overlap 
of side effects between HAART therapy and radiation therapy.
2.1.2.8
Patients must not have significantly diseased or obstructed gastrointestinal tract 
malabsorption, uncontrolled vomiting or diarrhea, or inability to swallow oral 
medication
2.1.2.9
Pregnant women are excluded from this study because Selinexor could have the 
potential for teratogenic or abortifacient effects. Because there is an unknown but 
potential risk for adverse events in nursing infants secondary to treatment of the mother 

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with Selinexor, breastfeeding should be discontinued if the mother is treated with 
Selinexor. These potential risks may also apply to temozolomide used in this study.
2.1.2.10 Patients with pre-existing known or suspected radiation sensitivity syndromes will be 
excluded due to potential confounding effect on outcome.
2.1.3
Recruitment Strategies
Both men and women and members of all races and ethnic groups are eligible for this trial. This 
study will be listed on NIH websites and www.clinicaltrials.gov. Participants will be recruited 
from the current patient population as well as referrals at NIH. Social media platforms managed 
by NIH/NCI may also be used to publicize the study. This protocol may be abstracted into a 
plain language announcement posted on NIH websites and on NIH social media platforms. 
2.2
SCREENING EVALUATION
2.2.1
Screening activities performed prior to obtaining informed consent
Minimal risk activities that may be performed before the subject has signed a consent include the 
following: 
•
Email, written, in person or telephone communications with prospective subjects 
•
Review of existing medical records to include H&P, laboratory studies, etc.  
•
Review of existing  MRI, x-ray, or CT images
•
Review of existing photographs or videos
•
Review of existing pathology specimens/reports from a specimen obtained for diagnostic 
purposes
2.2.2
Screening activities performed after a consent for screening has been signed
The following activities will be performed only after the subject has signed the consent for study 
# 01C0129 (Eligibility Screening and Tissue Procurement for the NIH Intramural Research 
Program Clinical Protocols). Assessments performed at outside facilities or on another NIH 
protocol within the timeframes below may also be used to determine eligibility once a patient has 
signed the consent.
•
All tumors will undergo central pathology review at NIH prior to study including 
molecular CNS panel whenever possible. Archival samples from surgery will be used for 
pathology review.
•
Clinical Evaluations (within 7 days prior to enrollment):
o
Complete history and physical exam completed by principal or associate 
investigator, including thorough documentation of signs and symptoms caused by 
the tumor, determination of Karnofsky performance scale (KPS), neurological 
function and mental status.
o
Vital signs: including height and weight
•
Laboratory Evaluations: Pre-treatment blood tests should be performed within 14 days 
prior to enrollment
o
Hematology: complete blood count (CBC) with differential,  PT/INR, PTT

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o
Chemistries:  bilirubin (total and direct), AST, ALT, LDH, BUN, alkaline 
phosphatase, albumin, serum creatinine, serum electrolytes, calcium, magnesium, 
phosphorus, uric acid , amylase and lipase
o
Hepatitis A, B and C serologies 
o
HIV antibody test screening. 
o
Urinalysis
o
Serum/urine pregnancy test:  required for females of childbearing potential
•
Conventional MRI (if needed based upon PI discretion)
2.3
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES
Registration and status updates (e.g. when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2, CCR Participant 
Registration & Status Updates found at: https://nih.sharepoint.com/sites/NCI-CCR-OCD-
Communications/SitePages/OEC-Administrative---Clinical-Research-(ADCR).aspx?Mode=Edit.
2.3.1
Treatment Assignment Procedures
Cohorts
Number
Name
Description
1
Cohort 1
Patients with newly diagnosed glioblastoma or 
gliosarcoma
Arms
Number
Name
Description
1
Experimental therapy
Selinexor with temozolomide and radiation
Arm assignment
Patients in cohort 1 will be directly assigned to arm 1. No randomization and stratification will 
be performed on this study.
2.4
BASELINE EVALUATION
Baseline assessments will be performed per Study Calendar.  Tests done at screening do not 
need to be repeated on baseline (C1D1) if performed within 7 days prior to enrollment except for 
physical exam, KPS, vital signs, neurological exam, performance and mental status, and urine 
pregnancy test. Screening laboratory evaluations do not need to be repeated if performed within 
14 days prior to enrollment. Please refer to section 2.2 for screening details.
•
Thyroid function tests: total T3, freeT4 and TSH+
•
Treatment planning CT/MRI scans: All patients will have radiation therapy treatment 
planning CT and MRI scans (as explained below). Treatment planning CT scans will be 
obtained with immobilization mask in place. 

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o
Conventional MRI: Conventional MRI including T1, T2, T2 FLAIR and 
postcontrast T1 as well as diffusion weighted (DWI) MRI (NOB Procedure 
DCE MRI) of the brain to occur within 2 weeks prior to study entry. If 
scans were obtained from another institution copies should be produced 
and maintained on file with the PI for future comparison, the patient 
however must receive MRI imaging as per above. MRI of the brain 
obtained within 2 weeks prior to enrollment can be used as baseline staging 
evaluations to be done at the NIH.
o
If initial imaging evaluation was greater than 3 weeks prior to referral, a 
diagnostic quality contrast enhanced MRI will be obtained for baseline 
staging evaluation.
•
Baseline quality of life (QOL) will be collected as per the MD Anderson Symptom 
Inventory for Brain Tumors (MDASI-BT) (Appendix D), PROMIS Depression, 
PROMIS Anxiety, and NeuroQoL assessments (Appendix E), PRO-CTCAE (Appendix 
F) within 1 week of study entry.
3
STUDY IMPLEMENTATION
3.1
STUDY DESIGN
3.1.1
Concurrent Therapy
•
Radiation therapy (RT) will be administered daily (Monday to Friday) in the Radiation 
Oncology Branch (ROB), NCI, unless the treatment schedule requires change in the event 
of inclement weather or federal holidays. 
•
Oral temozolomide will be taken as described in  section 3.2.1.
•
Selinexor  will be given during radiationas determined by dose level. Please refer to 
section 3.1.5 for details. All the protocol related follow-up appointments will occur at 
NCI ROB.
3.1.2
Adjuvant Therapy
•
Post RT, temozolomide will be given per standard of care. It could be given under this 
study or by patient’s primary oncologist. 

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3.1.3
Study Schema 
3.1.4
Dose Limiting Toxicity
A dose-limiting toxicity (DLT) is defined as a clinically significant adverse event assessed as 
unrelated to tumor progression, intercurrent illness or concomitant medications and meets any of 
the criteria below. Any DLT must be a toxicity considered at least possibly related to selinexor 
and the acute effects thereof. 
•
Any grade 3 or 4 toxicity as per CTCAE Criteria Version 5.0 during treatment and within 
30 days after completion of RT
•
Any grade 3 or 4 toxicity as per Section 14.1.2. RTOG acute morbidity during treatment 
and within 30 days after completion of RT 
•
Any toxicity at least possibly related to selinexor that causes a patient to miss consecutive 
radiation or temozolomide doses for 5 days.
3.1.5
Dose Escalation
This study will use a 3+3 design, with 3-6 patients enrolled per dose level to define maximum 
tolerated dose (MTD). The MTD is the dose level at which no more than 1 of up to 6 patients 
experience DLT within 1 month of completion of treatment, and the dose below that at which at 
least 2 (of ≤6) patients have DLT as a result of selinexor/RT/temozolomide. If a patient did not 
experience DLT and did not finish treatment, he or she will not be evaluable for toxicity and will 
be replaced in the dose level. Enrollment to a dose level would stop if 2 or more patients had a 
DLT.
The number of patients may be increased to 9 total patients at the MTD (provided no DLT) with 
a maximum of 21 evaluable patients enrolled and the minimum evaluable patients required will 
be 15.  The once weekly dosing schedule was based on the results of the KCP-330-004 study 
Arm D. The twice weekly dose of 60mg is from KCP-330-004 Arm C. 

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Dose Escalation Schedule of Selinexor
Dose Level
 
Level -1
80 mg on weeks 1, 4
Level 1
80 mg on weeks 1, 2, 4, 5
Level 2
60 mg twice a week on weeks 1, 2, 4, 5
Level 3
60 mg twice a week, weeks 1-6
All patients will receive 2Gy daily RT plus 75mg/m2 temozolomide.
Dose escalation will follow the rules outlined in the Table below.
Number of Patients 
with DLT
at a Given Dose Level
Escalation Decision Rule
0 out of 3
Enter up to 3 patients at the next dose level
> 2
Dose escalation will be stopped. This dose level 
will be declared the maximally administered 
dose (highest dose administered). Up to three 
(3) additional patients will be entered at the 
next lowest dose level if only 3 patients were 
treated previously at that dose.
1 out of 3
Enter up to 3 more patients at this dose level.
•
If 0 of these 3 patients experience DLT, 
proceed to the next dose level.
•
If 1 or more of this group suffer DLT, then 
dose escalation is stopped, and this dose is 
declared the maximally administered dose. 
Up to three (3) additional patients will be 
entered at the next lowest dose level if only 
3 patients were treated previously at that 
dose.
<1 out of 6 at highest 
dose level below the 
maximally administered 
dose
This is the MTD and is generally the 
recommended phase 2 dose. At least 6 patients 
must be entered at the recommended phase 2 
dose.

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3.1.6
Study Stopping Rule 
Accrual will be halted if there are ≥2 patients who miss consecutive doses of  RT or 
temozolomide for 5 days that are possibly attributable to the selinexor treatment. 
Prior to resumption of the study, PI will evaluate these events and determine the next course of 
action. 
3.2
DRUG ADMINISTRATION
3.2.1
Selinexor
At dose level 1, Selinexor will be administered orally at an initial dose of 80 mg. The first dose 
will be given on day 2 of radiation and will thereafter be administered weekly on the second day 
of weekly radiation on weeks 1, 2, 4, and 5. If dose level 1 is tolerated, the Selinexor dose will be 
escalated to 60 mg twice a week on weeks 1, 2, 4, 5 given on Monday and Thursday. The third 
and final dose level will be 60 mg administered twice a week (on Monday and Thursday of 
radiation) for 6 weeks.
Prophylactic concomitant treatments with a 5-HT3 antagonist and olanzapine may be 
administered per section 4. 
3.2.2
Temozolomide
Temozolomide will begin on the first day or evening prior of radiation and be administered 
orally daily at a dose of 75 mg/m2 during the radiation treatment. Temozolomide will continue 
until the completion of radiation and then will be stopped. 
Beginning 1-month post-RT, the adjuvant temozolomide will be given per standard of care.
3.2.2.1 CCR self – administered study drugs policy 
All oral self-administered study drug will be properly accounted for, handled, and disposed in 
accordance with existing federal regulations and principles of Good Clinical Practice. All oral 
study drugs will be recorded in the patient diary found in Appendix H or Appendix I. This will 
be used as a memory aide for subjects. The clinical research team will maintain the primary 
source record. Subjects should be asked to bring the diary as well as unused study drug and 
empty containers with them at each study visit. If a subject goes off study while at home, the 
research nurse will ensure and document the return of the unused oral study drug from the 
participant. Unused study drug will be disposed and destroyed per CC pharmacy SOPs.
3.3
DOSE MODIFICATIONS
3.3.1
Radiation Therapy
Modifications to the radiation treatment plan will be made at the discretion of the radiation 
oncologist. Ideally, radiation therapy will be delivered uninterrupted. Occasionally, deviations 
from this schedule may be required secondary to expected toxicity or life events. 

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3.3.2
Concurrent Systemic Agents
3.3.2.1
Selinexor
Supportive Care and Selinexor Dose Adjustment Guidelines for AEs related to Selinexor a,b
Toxicity and Intensity
Supportive Care and Dose Adjustment 
Guidelines
Fatigue
Grade 1 or Grade 2 lasting ≤7 days
Maintain dose. Rule out other causes. If found 
to be anemic and symptomatic, consider 
transfusions for hemoglobin >8 g/dL (Grade 
<3).
Grade 2 lasting >7 days or Grade ≥3
Rule out other causes. If found to be anemic 
and symptomatic, consider transfusions for 
hemoglobin >8 g/dL (Grade <3); transfusions 
usually indicated for hemoglobin <8 g/dL 
(Grade ≥3). Stop Selinexor.
 
Anorexia or Weight Loss
Grade 1 weight loss or Grade 2 anorexia and 
weight loss
Maintain dose. Rule out other causes. 
Consider nutritional consultation and utilize 
nutritional supplements. Should consider 
olanzapine 2.5 mg to 5 mg once a day if the 
weight loss is rapid.
Grade 2 weight loss or Grade ≥3 anorexia and 
weight loss
Rule out other causes. Consider nutritional 
consultation and utilize nutritional 
supplements or consider appetite stimulants 
including olanzapine 2.5 mg to 5mg once a 
day.
Stop Selinexor. 
Nausea, Acute
Grade 1 or 2 (If intolerable or persistent 
Grade 2 not responsive to supportive care 
follow guidelines for Grade 3)
Maintain dose. Rule out other causes. Utilize 
any additional anti-nausea needs to 
supplement breakthrough nausea
Grade 3
Rule out other causes. Utilize additional anti-
nausea meds to supplement the breakthrough 
nausea 

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Toxicity and Intensity
Supportive Care and Dose Adjustment 
Guidelines
Stop Selinexor.
Hyponatremia
Grade 1 (sodium levels <Normal to 130 
mmol/L)
Maintain dose. Rule out other causes 
including drug (e.g. diuretics) effects.  Be 
certain that reported sodium level is corrected 
for concurrent hyperglycemia (serum glucose 
>150mg/dL). 
Treat hyponatremia per institutional 
guidelines including dietary review. Consider 
addition of salt tablets to patient’s diet.
Grade 3 with sodium levels <130-120 
mmol/L without symptoms
Rule out other causes including drug (e.g. 
diuretics) effects.  Be certain that reported 
sodium level is corrected for concurrent 
hyperglycemia (serum glucose >150mg/dL). 
If (corrected) sodium is Grade ≤3 and 
continues to be asymptomatic then patient 
may continue current dosing without 
interruption provided that IV saline and/or 
salt tablets are provided and patient is 
followed closely.
Stop Selinexor.
Grade 3 with sodium levels <130-120 
mmol/L with symptoms or Grade 4 (<120 
mmol/L)
Rule out other causes including drug (e.g. 
diuretics) effects.  Be certain that reported 
sodium level is corrected for concurrent 
hyperglycemia (serum glucose >150mg/dL). 
Stop Selinexor. 
Diarrhea
Grade 1
Maintain dose. Rule out other causes 
including drug effects. Treat per institutional 
guidelines.
Grade 2
Rule out other causes including drug effects. 
Treat per institutional guidelines with anti-
diarrheals. Interrupt Selinexor dosing until 
resolved to Grade 1 or baseline.

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Toxicity and Intensity
Supportive Care and Dose Adjustment 
Guidelines
For first occurrence, restart Selinexor at 
current dose. 
For ≥ second occurrence, reduce Selinexor by 
1 dose level.
Grade 3 or 4
Rule out other causes including drug effects. 
Treat per institutional guidelines with anti-
diarrheals.
Stop Selinexor.
 
Thrombocytopenia
See below section 3.3.2.1.1
Neutropenia
See below section 3.3.2.1.1
Anemia
Treat per institutional guidelines including blood transfusions and/or erythropoietins. Consider 
transfusing for symptoms with hemoglobin >8g/dL (Grade <3) or for any Grade 3 
(hemoglobin <8 g/dL). If possible, maintain Selinexor dose as long as patient is clinically 
stable, but if a dose reduction or interruption is desired, consult with the Principal Investigator.
Other Selinexor-related adverse events
Grade 1 or 2
Rule out other causes. Maintain dose. Initiate 
treatment and/or standard supportive care per 
institutional guidelines.
Grade 3 or 4
Rule out other causes.
Isolated values of Grade ≥3 alkaline 
phosphatase does not require dose 
interruption. Determination of liver versus 
bone etiology should be made and evaluation 
of gamma-glutamyl transferase, 5’-
nucleotidase, or other liver enzymes should be 
performed.
Stop Selinexor.
a For all Grade ≥3 hematological or non-hematological AEs that are NOT Selinexor or 
Temozolomide related, after consultation with the Medical Monitor and at the discretion of the 
Investigator, selinexor may be maintained

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b For all Selinexor-related AEs, if the below prescribed dose reductions/interruptions result in a 
stabilization of ≥4 weeks, a re-escalation may be considered after approval from the Medical 
Monitor.
All dose modifications should be based on the worst preceding toxicity. 
Note: It is strongly encouraged that the Investigator dose reduces or interrupts one drug at a time 
for those AEs that are thought to have multifactorial causes. 
3.3.2.1.1 Infection
Patients with active uncontrolled or suspected infections should have treatment withheld until the 
infection has clinically resolved and/or the patient is clinically stable. When ready to resume 
dosing, treatment may continue at the original dose. Patients may continue antibiotic therapy for 
prolonged periods while re-initiating their treatment at the discretion of the Investigator.
3.3.2.1.2 Renal Insufficiency
Baseline renal insufficiency does not appear to affect tolerability of Selinexor and renal 
dysfunction should not preclude continued dosing with Selinexor, even for patients on dialysis. If 
a patient is undergoing dialysis, Selinexor should be given after dialysis procedure because the 
effect of dialysis on Selinexor plasma levels has not yet been studied. Selinexor can lead to 
increased creatinine and the majority of these cases are associated with hypovolemic conditions 
(e.g., represent “pre-renal” azotemia). Dose modifications or interruptions and appropriate 
hydration typically reverse the increased creatinine.
3.3.2.1.3 Conditions not requiring Selinexor dose reduction
The following conditions are exceptions to the dose-modification guidelines. Selinexor does not 
need to be held for alopecia of any grade, or for electrolytes or serum analyte (e.g., urate) 
abnormalities that are reversible with standard interventions. 
3.3.2.2
Temozolomide (TMZ)
3.3.2.2.1 During concomitant radiotherapy
A complete blood count should be obtained weekly. Adjustments to the dose of Temozolomide 
and Selinexor will be made at the direction of the PI or study chairperson.
Toxicity and Intensity
Supportive Care and Dose Adjustment 
Guidelines
Platelets
>75k
Continue both drugs.
Grade 2, >50-75k
Hold TMZ
Hold Selinexor
Continue RT.
Recheck CBC, when platelets >75k restart 
TMZ and selinexor 

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Grade 3, 25-50k
Hold TMZ.
Discontinue Selinexor.
Continue RT.
Recheck CBC, when platelets >75k restart 
TMZ 
Grade 4, <25k
Hold TMZ
Discontinue Selinexor
Hold RT
Recheck CBC, when platelets >50k restart RT
When platelets >75 k restart TMZ 
ANC
>1.5
Continue both drugs
Grade 2, >1-1.5
Hold TMZ
Hold Selinexor
Continue RT
Recheck CBC when ANC 1.5 restart TMZ  
and selinexor 
Grade 3, 0.5-1
Hold TMZ
Discontinue Selinexor
Continue RT
Recheck CBC, when ANC >1.5 restart TMZ 
Grade 4, <0.5
Hold TMZ
Discontinue Selinexor
Continue RT
Recheck CBC, when ANC >1,5 restart TMZ, 
3.3.2.2.2 Following the completion of chemoradiation
 Beginning 1-month post-RT, the adjuvant temozolomide will be given per standard of care.
3.4
QUESTIONNAIRES (FOR ENGLISH SPEAKING PATIENTS ONLY)
MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT) (Appendix D) will be 
performed at baseline, at completion of radiation and at all subsequent follow-up visits. 

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PROMIS Depression, PROMIS Anxiety, and NeuroQoL assessments (Appendix E and 
Appendix F) will be performed at baseline, at completion of radiation and at all subsequent 
follow-up visits. 
PRO-CTCAE (Appendix G): Patients will complete a baseline PRO-CTCAE before starting 
treatment, at completion of radiation and at all subsequent follow-up visits if the patient is able. 
It takes 5-10 minutes to complete each questionnaire. It will only be completed by the patient, 
unless changes in vision or weakness make this difficult. If this occurs, then the caregiver may 
read the questions to the patient or assist with marking the answers as described by the patient. A 
patient caregiver may complete the questionnaires as a patient-preference proxy if the patient’s 
deficits preclude self-report. 
All questionnaires are allowed to be completed within +/-7 days from the scheduled dates.
Every attempt will be made to collect this data from every patient at each time point.  If the 
patient is a non-English speaker the data will not be collected.

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3.5
STUDY CALENDAR
Follow-up (Total 3 yrs) 8, 10
Procedure
Screening
Baseline1
Radiation2
(every day 
up to 6 
weeks)
1 month
Every 2 
months 
for 2 yrs
Every 3 
months 
for 3rd yr
History & PE 
X
X
X
X
X
Karnofsky Performance
X
X
X
X
X
Neurological function 
& Mental Status
X
X
X
X
X
Vital signs incl Weight
X
X
X
X
X
X
Height
X
Pathology review incl 
molecular CNS panel
X
Treatment
On treatment visit 
(OTV) evaluation once 
per week
X
Temozolomide (Daily)3
X
Selinexor 4
X
Toxicity assessment5, 9
X
X
X
X
Labs (Please refer section 2.2.2 for details)
Hematology6a
X
X
X
X
X
X
Chemistries6b
X
X
X
X
X
X
Thyroid function tests 
X
Pregnancy Test 
(urine/serum)
X
X
Hepatitis A, B and C 
testing
X
HIV testing
X
Radiographic (Please refer section 2.4 for details)
MRI 
X
X
X
X
X
CT scans
X
Questionnaires (Please refer section 3.4 for details)
QoL questionnaires per 
MDASI-BT (Appendix 
D)7
X
X
X
X
X
PROMIS Depression, 
PROMIS Anxiety, and 
NeuroQoL (Appendix 
E) 7
X
X
X
X
X
PRO-CTCAE 
(Appendix F) 7
X
X
X
X
X
1
Tests done at screening do not need to be repeated on baseline (C1D1) if performed within 7 days 
prior to enrollment except physical exam, KPS, vital signs, neurological exam, performance and 
mental status, and urine pregnancy test. Screening laboratory evaluations do not need to be repeated 
if done within 14 days prior to enrollment.

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2
Patients will be treated with 2Gy daily RT plus 75mg/m2 temozolomide for six weeks with 
Selinexor given once or twice a week depending on dose level. 
3
Regarding temozolomide dosing details, please refer to section 3.2.2.
4
Administered per section 3.1.5.
5
Assessment of acute toxicity (CTCAE Version 5.0 and RTOG Acute Morbidity score. (see 
Appendix B and Appendix C) 
6
Laboratory evaluation weekly during radiation.
a.
Complete blood count with differential and platelets, PT/INR, PTT
b.
Serum chemistries: LDH, AST, ALT, alkaline phosphatases, bilirubin (total and direct), 
BUN, serum creatinine, serum electrolytes, glucose, calcium, magnesium, phosphorous, 
uric acid, albumin, amylase, lipase 
7
QOL assessment will be performed at baseline, at completion of radiation and at all subsequent 
follow-up visits. The questionnaires are allowed to be completed within +/-7 days from the 
scheduled dates.
8
May be completed by remote visit with a member of the study team (e.g., if the patient is not able 
to return to the NIH CC). A patient may be referred to their local provider or asked to come to the 
NIH CC for an in-person assessment, if clinically indicated, and at the discretion of the PI.  In the 
case of any visits with participants’ local providers, records will be obtained. Follow-up 
evaluations should occur at one month after the completion of therapy, followed by at least every 
2-month intervals for the first 2 year(s), and then at least every 6 months thereafter for a total of 3 
years following completion of radiation/ Temozolomide/ Selinexor. 
9
Toxicity assessment, vital signs and weight measurement may be done weekly during the on 
treatment visit and as needed.
10
All follow-up appointments will take place within +/- 7 days of the designated timepoint.  

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3.6
RADIATION THERAPY GUIDELINES 
3.6.1
Scheduling
Radiation therapy will be administered daily Monday-Friday at NCI ROB unless the treatment 
schedule requires amendment in the event of inclement weather or federal holidays. All the 
protocol related follow-up appointments will occur at NCI ROB at the NIH Clinical Center.
3.6.2
Technique
Radiation therapy dose will be administered on consecutive treatment days, 5 fractions per week 
via a linear accelerator using 6 MV photons or greater. Interruptions for holidays will be 
permitted, and any missed days will be added on to the end of treatment. CT simulation will be 
performed in the treatment position with the patient immobilized using a thermoplastic mask. 
Both EORTC and RTOG treatment volumes are permitted as described below:
EORTC treatment volumes (single phase)
RTOG treatment volumes (two phases)
Single Phase (Treated to 60 Gy in 30 fractions)
Phase I (Treated to 46 Gy in 23 fractions)
GTV1:  Surgical resection cavity plus any 
residual enhancing tumor (postcontrast T1 
weighted MRI scans) plus surrounding 
edema (hyperintensity on T2 or FLAIR MRI 
scans).
CTV1:  GTV1 plus a margin of 2 cm (if no 
surrounding edema is present, the CTV is the 
contrast enhancing tumor plus 2.5 cm.
PTV1:  CTV plus a margin of 3-5 mm
Phase II (Treated to 14 Gy in 7 fractions)
GTV:  Surgical resection cavity plus any 
residual enhancing tumor (postcontrast T1 
weighted MRI scans).
CTV:  GTV plus a margin of 2 cm
PTV:  CTV plus a margin of 3-5 mm
GTV2:  Surgical resection cavity plus any 
residual enhancing tumor (postcontrast T1 
weighted MRI scans)
CTV2:  GTV2 plus a margin of 2 cm
PTV2:  CTV2 plus a margin of 3-5 mm
3.6.3
Target coverage and dose limits
The volume of PTV covered by the prescription dose must represent ≥ 95% of the PTV. A 
variation of ≥ 90% coverage of the PTV will be accepted. As per ICRU criteria, the max point 
dose shall not exceed 107% of the prescribed dose. 
3.6.4
Critical structures
The organs at risk in the field to be contoured include brain, brainstem, optic nerves, and optic 
chiasm. Normal tissue dose limits will be employed as per table below:

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OAR
Objective
Brainstem
Dmax≤60 Gy
1-10 cc> 59 Gy (Periphery)
Chiasm
Dmax<55 Gy
Cochlea
Ideally one side mean <45 Gy
Eyes
Macula<45 Gy
Optic Nerves
Dmax <55 Gy
3.7
COST AND COMPENSATION 
3.7.1
Costs
NIH does not bill health insurance companies or participants for any research or related clinical 
care that participants receive at the NIH Clinical Center.  If some tests and procedures are 
performed outside the NIH Clinical Center, participants may have to pay for these costs if they 
are not covered by an insurance company.  Medicines that are not part of the study treatment will 
not be provided or paid for by the NIH Clinical Center.    
3.7.2
Compensation
There will not be any compensation as part of the study.
3.7.3
Reimbursement 
The NCI will cover the costs of some expenses associated with protocol participation.  Some of 
these costs may be paid directly by the NIH and some may be reimbursed to the 
participant/guardian as appropriate.  The amount and form of these payments are determined by 
the NCI Travel and Lodging Reimbursement Policy.   
3.8
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA
Prior to removal from study, effort must be made to have all subjects complete a safety visit 
approximately 30 days following the last dose of study therapy.
3.8.1
Criteria for removal from protocol therapy
•
Completion of 6 weeks of RT
•
Progressive disease as defined in 6.3.1 
•
Participant requests to be withdrawn from active therapy
•
Unacceptable Toxicity as defined in section 3.3
•
Investigator discretion
•
Positive pregnancy test

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3.8.2
Off-Study Criteria
•
Completed study follow-up period
•
Participant requests to be withdrawn from study
•
Death
•
Investigator discretion 
•
Non-compliance with follow-up visits or protocol mandated procedures 
•
Participant lost to follow up
•
Investigator decision to end the study
3.8.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she fails to return for three scheduled 
visits and is unable to be contacted by the study site staff. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
•
The site will attempt to contact the participant and reschedule the missed visit within two 
weeks and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study.
•
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, an IRB approved certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented in 
the participant’s medical record or study file. 
•
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.
4
CONCOMITANT MEDICATIONS/MEASURES
•
Prophylactic concomitant treatments with a 5-HT3 antagonist and olanzapine 5 mg for 
men and 2.5 mg for women  must be provided 3 days prior to and during treatment with 
each dose of selinexor. Olanzapine may be administered as needed on days 6 and 7 
during week of selinexor treatment.
•
PJP prophylaxis should be given during the concurrent chemoradiation phase of 
treatment. Acceptable forms of treatment include oral trimethoprim-sulfamethoxazole 
and aerosol pentamidine as is left to the discretion of the treating physician. 
•
Other cancer chemotherapy, immunotherapy, or investigational agents may NOT be 
administered to patients in the active course of treatment on this study. 
•
Patients will receive corticosteroids as needed for symptoms of cerebral edema as 
clinically indicated. Attempts to wean patients from steroids should be made as indicated 
by improvement or stabilization of neurologic symptoms. Any initiation of steroids or 
increase in dose thereof will be documented. 
•
All patients with a seizure history will be maintained on their existing anticonvulsant 
medication.

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•
Radiation therapy side effects include fatigue, nausea and vomiting and possible 
worsening of preexisting neurological symptoms. These will be managed using general 
best supportive care and corticosteroids may be initiated at the discretion of the treating 
radiation oncologists and taper as needed depending on clinical status once irradiation has 
been completed. 
•
The ROB staff physician, nurse practitioner and research nurse will frame the support 
infrastructure required to assist with the patient`s care in the event of serious treatment 
toxicity. The pain and palliative team, will be consulted as needed to address end of life 
issues and disposition as has been standard procedure for all ROB patients to date.
5
CORRELATIVE STUDIES FOR RESEARCH
None.
6
DATA COLLECTION AND EVALUATION 
6.1
DATA COLLECTION
The PI will be responsible for overseeing entry of data into a 21 CFR Part 11-compliant data 
capture system provided by the NCI CCRand ensuring data accuracy, consistency and timeliness. 
An enrollment log will be maintained in the regulatory binder/file which is the only location of 
personal identifiers with unique subject identification number. Imaging will be digitally archived 
and processed using computer software in the Radiology department of the Clinical Center, NIH, 
and the Radiation Oncology Branch, NCI. The principal investigator, associate 
investigators/research nurses and/or a contracted data manager will assist with the data 
management efforts. Primary and final analyzed data will have identifiers so that research data 
can be attributed to an individual human subject participant.
All adverse events, including clinically significant abnormal findings on laboratory evaluations, 
regardless of severity, will be followed until return to baseline or stabilization of event. 
Document AEs from the first study intervention, Study Day 1, through 30 days after the subject 
received the last study drug administration.  
An abnormal laboratory value will be recorded in the database as an AE only if the laboratory 
abnormality is characterized by any of the following:
•
Results in discontinuation from the study
•
Is associated with clinical signs or symptoms 
•
Requires treatment or any other therapeutic intervention
•
Is associated with death or another serious adverse event, including hospitalization
•
Is judged by the Principal Investigator to be of significant clinical impact
•
If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome.
End of study procedures: Data will be stored according to HHS, FDA regulations, and NIH 
Intramural Records Retention Schedule as applicable. 

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Loss or destruction of data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, this will be reported expeditiously per 
requirements in section 7.2.1. 
6.2
DATA SHARING PLANS
6.2.1
Human Data Sharing Plan
What data will be shared?
I will share human data generated in this research for future research as follows:
•
Coded, linked data in an NIH-funded or approved public repository.
•
Coded, linked data in BTRIS (automatic for activities in the Clinical Center)
•
Identified or coded, linked  data with approved outside collaborators under appropriate 
agreements.
How and where will the data be shared? 
Data will be shared through:
•
An NIH-funded or approved public repository. Such as: clinical trial.gov
•
BTRIS (automatic for activities in the Clinical Center)
•
Approved outside collaborators under appropriate individual agreements.
•
Publication and/or public presentations.
When will the data be shared?
•
 Before publication.
•
At the time of publication or shortly thereafter.
6.2.2
Genomic Data Sharing Plan
NIH Genomic Data Sharing Policy will not apply for this protocol as no genetic/genomic testing 
is performed.
6.3
RESPONSE CRITERIA
6.3.1
Modified RANO Response Criteria
Response will be assessed by Modified RANO criteria and as such, the first imaging following 
completion of radiation will be considered the baseline for response assessment as per Ellingson 
et al. Neurotherapeutics 2017[25]. 

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Response
Modified RANO response Criteria
Complete response (CR)
Requires all of the following:
1.Disappearance of all enhancing measurable 
and non-measurable disease sustained for at 
least 4 weeks. 
2. No new lesions.
3.Patients must be off corticosteroids (or on 
physiologic replacement doses only).
4 .Stable or improved clinical assessments 
(i.e. neurological examinations).
Note: Patients with non-measurable
disease only cannot have
achieve CR; the best response
possible is SD
Partial Response (PR)
Requires all of the following:
1. ≥50% decrease in sum of products of 
perpendicular diameters or ≥65% decrease in 
total volume of all measurable enhancing 
lesions compared with baseline, sustained for 
at least 4 weeks. If the second scan exhibits 
PD with respect to the “preliminary PR” scan, 
then the response is not sustained, noted as 
pseudoresponse, PsR, and is now considered 
“preliminary PD” (note confirmed PD 
requires at least two sequential increases in 
tumor volume). If the second scan exhibits 
SD, PR, or CR, it is considered a durable 
PR and the patient should continue on therapy 
until confirmed PD is observe
2. No new lesion.
3. Steroid dose should be the same or lower 
compared with baseline scan.
 4. Stable or improved clinical assessments.

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Response
Modified RANO response Criteria
Progressive Disease (PD)
1. At least two sequential scans separated by 
at ≥4 weeks both exhibiting ≥25% increase 
in sum of products of perpendicular 
diameters or ≥40% increase in total volume 
of enhancing lesions.
2. In the case where the baseline or best 
response demonstrates no measurable 
enhancing disease (visible or not visible), 
then any new measurable (>10mm x 10mm) 
enhancing lesions are considered 
PD after confirmed by a subsequent scan ≥4 
weeks exhibiting ≥25% increase in sum of 
products of perpendicular diameters or ≥40% 
increase in total volume of enhancing lesions 
relative to the scan first illustrating new 
measurable disease. 
3.Clear clinical deterioration not attributable 
to other causes apart from tumor (e.g. 
seizures, medication adverse effects, therapy 
complications, stroke, infection) or 
attributable to changes in steroid dose.
 4.Failure to return for evaluation as a result 
of death or deteriorating condition.
Stable disease (SD)
1. Does not qualify for CR, PR, or PD as 
defined above. Note this also applies to 
patients that demonstrate PsR when the 
confirmation scan does not show PD or PsP 
when the confirmation scan does not show 
PR/CR.
 2. In the event that corticosteroid dose was 
increased (for new symptoms/signs) without 
confirmation of disease progression on 
neuroimaging, and subsequent follow-up 
imaging shows that the steroid increase was 
required because of disease progression, the 
last scan considered to show stable disease 
will be the scan obtained when the 
corticosteroid dose was equivalent to the 
baseline dose.
6.4
TOXICITY CRITERIA
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study. RTOG morbidity score will be used for radiation related toxicity 

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(Appendix B and Appendix C).  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE 
reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 
5.0. A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm).
7
NIH REPORTING REQUIREMENTS/DATA SAFETY MONITORING PLAN
7.1
DEFINITIONS
Please refer to definitions provided in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements.
7.2
OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING 
7.2.1
Expedited Reporting
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802 Non-Compliance Human Subjects Research found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements. Note: Only IND Safety 
Reports that meet the definition of an unanticipated problem or present new information that 
might affect the willingness of participants to enroll or remain on the study will need to be 
reported per these policies.
7.2.2
IRB Requirements for PI Reporting at Continuing Review
Please refer to the reporting requirements in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements. 
7.3
NCI CLINICAL DIRECTOR REPORTING 
Problems expeditiously reviewed by the OHSRP in the NIH eIRB system will also be reported to 
the NCI Clinical Director/designee; therefore, a separate submission for these reports is not 
necessary.
In addition to those reports, all deaths that occur within 30 days after receiving a research 
intervention should be reported via email unless they are due to progressive disease.  
To report these deaths, please send an email describing the circumstances of the death to 
NCICCRQA@mail.nih.gov within one business day of learning of the death
7.4
NIH REQUIRED DATA AND SAFETY MONITORING PLAN
7.4.1
Principal Investigator/Research Team 
The clinical research team will meet on a  weekly basis when patients are being actively treated 
on the trial to discuss each patient. Decisions about dose level enrollment and dose escalation if 
applicable will be made based on the toxicity data from prior patients. 

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All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Events meeting requirements for expedited reporting as described in 
section 7.2.1 will be submitted within the appropriate timelines.  
The principal investigator will review adverse event and response data on each patient to ensure 
safety and data accuracy. The principal investigator will personally conduct or supervise the 
investigation and provide appropriate delegation of responsibilities to other members of the 
research staff. 
8
SPONSOR PROTOCOL/SAFETY REPORTING
8.1
DEFINITIONS
8.1.1
Adverse Event 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product (ICH E6 (R2)).
8.1.2
Treatment-emergent adverse event (TEAE)
Any event that was not present prior to the initiation of study treatment or any event already 
present that worsens in either intensity or frequency following exposure to study treatment. 
8.1.3
Serious Adverse Event (SAE)
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following:
•
Death,
•
A life-threatening adverse event (see 8.1.4)
•
Inpatient hospitalization or prolongation of existing hospitalization
o
A hospitalization/admission that is pre-planned (i.e., elective or scheduled surgery 
arranged prior to the start of the study), a planned hospitalization for pre-existing 
condition, or a procedure required by the protocol, without a serious deterioration in 
health, is not considered a serious adverse event.
o
A hospitalization/admission that is solely driven by non-medical reasons (e.g., 
hospitalization for patient or subject convenience) is not considered a serious adverse 
event. 
o
Emergency room visits or stays in observation units that do not result in admission to 
the hospital would not be considered a serious adverse event. The reason for seeking 
medical care should be evaluated for meeting one of the other serious criteria.
•
Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions
•
A congenital anomaly/birth defect.

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•
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition.
8.1.4
Life-threatening 
An adverse event or suspected adverse reaction is considered "life-threatening" if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a 
more severe form, might have caused death. (21CFR312.32).
8.1.5
Severity
The severity of each Adverse Event will be assessed utilizing the CTCAE version 5.0.
8.1.6
Relationship to Study Product
All AEs will have their relationship to study product assessed using the terms:  related or not 
related.  
•
Related – There is a reasonable possibility that the study product caused the adverse 
event. Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study product and the adverse event.
•
Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event.
8.2
ASSESSMENT OF SAFETY EVENTS
AE information collected will include event description, date of onset, assessment of severity 
and relationship to study product and alternate etiology (if not related to study product), date of 
resolution of the event, seriousness and outcome. The assessment of severity and relationship to 
the study product will be done only by those with the training and authority to make a diagnosis 
and listed on the Form FDA 1572 as the site principal investigator or sub-investigator.  AEs 
occurring during the collection and reporting period will be documented appropriately regardless 
of relationship.  AEs will be followed through resolution.
SAEs will be:
•
Assessed for severity and relationship to study product and alternate etiology (if not 
related to study product) by a licensed study physician listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator.
•
Recorded on the appropriate SAE report form, the medical record and captured in the 
clinical database.
•
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the site principal investigator or sub-investigator.
For timeframe of recording adverse events, please refer to section 6.1. All serious adverse events 
recorded from the time of first investigational product administration must be reported to the 
sponsor with the exception of any listed in section 8.4.

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8.3
REPORTING OF SERIOUS ADVERSE EVENTS
Any AE that meets a protocol-defined serious criteria or meets the definition of Adverse Event 
of Special Interest that require expedited reporting must be submitted immediately (within 24 
hours of awareness) to OSRO Safety using the CCR SAE report form. Any exceptions to the 
expedited reporting requirements are found in section 8.4.
All SAE reporting must include the elements described in 8.2.
SAE reports will be submitted to the Center for Cancer Research (CCR) at: 
OSROSafety@mail.nih.gov and to the CCR PI and study coordinator.  CCR SAE report form 
and instructions can be found at: https://nih.sharepoint.com/:u:/r/sites/NCI-CCR-OCD-
Communications/SitePages/Forms-and-Instructions.aspx?csf=1&web=1&e=uWBXtI
Following the assessment of the SAE by OSRO, other supporting documentation of the event 
may be requested by the OSRO Safety and should be provided as soon as possible.
8.4
WAIVER OF EXPEDITED REPORTING TO CCR
Progression of the malignancy disease (including fatal outcomes) should NOT be reported as an 
SAE during the study or within the safety reporting period. Any sudden or unexplained death 
should be reported as an SAE. If there is any uncertainty about a finding being due solely to 
progression of malignancy disease, the finding should be reported as an AE or SAE, as 
appropriate. 
8.5
SAFETY REPORTING CRITERIA TO THE PHARMACEUTICAL COLLABORATORS
Reporting will be per the collaborative agreement. 
8.6
REPORTING PREGNANCY 
All required pregnancy reports/follow-up to OSRO will be submitted to: 
OSROSafety@mail.nih.gov and to the CCR PI and study coordinator.  Forms and instructions 
can be found here: https://nih.sharepoint.com/:u:/r/sites/NCI-CCR-OCD-
Communications/SitePages/Forms-and-Instructions.aspx?csf=1&web=1&e=uWBXtI
8.6.1
Maternal exposure
If a patient becomes pregnant during the course of the study, the study treatment should be 
discontinued immediately, and the pregnancy reported to the Sponsor no later than 24 hours of 
when the Investigator becomes aware of it. The Investigator should notify the Sponsor no later 
than 24 hours of when the outcome of the Pregnancy become known,
Pregnancy itself is not regarded as an SAE. However, congenital abnormalities or birth defects 
and spontaneous miscarriages that meet serious criteria (section 8.1.3) should be reported as 
SAEs. 
The outcome of all pregnancies should be followed up and documented.
8.6.2
Paternal exposure
Male patients should refrain from fathering a child or donating sperm during the study and for 
one month after the last dose of temozolomide.

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Pregnancy of the patient’s partner is not considered to be an AE. The outcome of all pregnancies 
occurring from the date of the first dose until one month after last dose of temozolomide should, 
if possible, be followed up and documented. Pregnant partners may be offered the opportunity to 
participate in an institutional pregnancy registry protocol (e.g., the NIH IRP pregnancy registry 
study) to provide data about the outcome of the pregnancy for safety reporting purposes.
8.7
REGULATORY REPORTING FOR STUDIES CONDUCTED UNDER CCR SPONSORED IND
Following notification from the investigator, CCR, the IND sponsor, will report any suspected 
adverse reaction that is both serious and unexpected.  CCR will report an AE as a suspected 
adverse reaction only if there is evidence to suggest a causal relationship between the study 
product and the adverse event.  CCR will notify FDA and all participating investigators (i.e., all 
investigators to whom the sponsor is providing drug under its INDs or under any investigator’s 
IND) in an IND safety report of potential serious risks from clinical trials or any other source, as 
soon as possible, in accordance to 21 CFR Part 312.32. 
All serious events will be reported to the FDA at least annually in a summary format.
8.8
SPONSOR DEVIATION REPORTING
A Protocol Deviation is defined as any non-compliance with the clinical trial Protocol, Manual 
of Operational Procedures (MOP) and other Sponsor approved study related documentsGCP, or 
protocol-specific procedural requirements on the part of the participant, the Investigator, or the 
study site staff inclusive of site personnel performing procedures or providing services in support 
of the clinical trial.
It is the responsibility of the study Staff to document any protocol deviation identified by the 
Staff or the site Monitorin the CCR Protocol Deviation Tracking System (PDTS) online 
application. The entries into the PDTS online application should be timely, complete, and 
maintained per CCR PDTS user requirements. In addition, any deviation to the protocol should 
be documented in the participant’s source records and reported to the reviewing IRB per their 
guidelines. OSRO required protocol deviation reporting is consistent with E6(R2) GCP: 
Integrated Addendum to ICH E6(R1): 4.5 Compliance with Protocol; 5.18.3 (a), and 5.20 
Noncompliance; and ICH E3 16.2.2 Protocol deviations.
9
CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure:
•
that the rights of the participants are protected; 
•
that the study is implemented per the approved protocol, Good Clinical Practice and 
standard operating procedures; and, 
•
the quality and integrity of study data and data collection methods are maintained.  
Monitoring for this study will be performed by NCI CCR Office of Sponsor and Regulatory 
Oversight (OSRO) and Regulatory Oversight Support (SROS) Services contractor. Clinical site 
monitoring activities will be based on OSRO standards, FDA Guidance E6(R2) Good Clinical 
Practice: Integrated Addendum to ICH E6(R1) March 2018, and applicable regulatory 
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Details of clinical site monitoring will be documented in a Clinical Monitoring Plan (CMP) 
developed by OSRO. CMPs will be protocol-specific, risk-based and tailored to address human 
subject protections and integrity of the study data. OSRO will determine the intensity and 
frequency of monitoring based on several factors, including study type, phase, risk, complexity, 
expected enrollment rate, and any unique attributes of the study and the site. The Sponsor will 
conduct a periodic review of the CMP to confirm the plan's continued appropriateness. A change 
to the protocol, significant or pervasive non-compliance with GCP, or the protocol may trigger 
CMP updates.
OSRO SROS Monitoring visits and related activities will be conducted throughout the life cycle 
of each protocol. The first activity is before the study starts to conduct a Site Assessment Visit 
(SAV) (as warranted), followed by a Site Initiation Visit (SIV), Interim Monitoring Visit(s) 
(IMVs), and a study Close-Out Visit (COV).
Some monitoring activities may be performed remotely, while others will occur at the study 
site(s). Monitoring visit reports will describe visit activities, observations, and associated action 
items or follow-up required for resolution of any issues, discrepancies, or deviations. Monitoring 
reports will be distributed to the study PI, NCI CCR QA, CCR Protocol Support Office, 
coordinating center (if applicable), and the Sponsor regulatory file.
The site Monitor will inform the study team of any deviations observed during monitoring visits. 
If unresolved, the Monitor will request that the site Staff enter the deviations in the CCR 
Protocol Deviation Tracking System (PDTS) for deviation reporting to the Sponsor and as 
applicable per institutional and IRB guidance.
10 STATISTICAL CONSIDERATIONS
10.1 STATISTICAL HYPOTHESIS
10.1.1 Primary Endpoint
Define the maximum tolerated dose (MTD) of Selinexor given concurrently with radiation and 
temozolomide. Assessment of toxicities for dose escalation will occur for 30 days following the 
completion of RT. 
10.1.2 Secondary Endpoint
Define the dose-limiting toxicities including effects on QOL and neurocognition in the setting of 
the addition of Selinexor to concurrent radiation therapy and temozolomide.
10.2 SAMPLE SIZE DETERMINATION 
The primary objective of this trial is to determine the safety, toxicity profile, DLT and maximum 
tolerated dose (MTD) of Selinexor given concurrently alongside temozolomide and radiation in 
patients with newly diagnosed glioblastoma patients. There are 3 planned dose levels for this 
trial that will enroll 1 to 6 patients each using the 3+3 design to define the MTD. The MTD will 
be based on the assessment of DLT within one month following the irradiation, and will be 
defined as the dose level at which less than one-third of patients (0/3 or 0-1/6 patients) treated at 
that dose level experience a DLT, with the next higher dose level demonstrating a one-third or 
greater number of patients (≥ 2/3 or ≥ 2/6 patients) having DLT. If a patient did not experience 
DLT and did not finish therapy, he or she will not be evaluable for determination of the MTD 

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and will be replaced in the dose level. An additional 3 to 6 patients will be enrolled at the MTD, 
so that a total of 9 patients will be treated at this dose to better characterize the clinical activity of 
this combination in this patient population. Thus, if all 3 dose levels are evaluated (6 patients per 
dose level with 9 total patients at the MTD or maximum administered dose), a maximum of 21 
evaluable patients will be enrolled. Similarly, if all dose levels are evaluated, the minimum 
number of evaluable patients required will be 15. To compensate for inevaluable patients, an 
additional 3 patients may be enrolled. Thus, a maximal of 24 patients are targeted for this study. 
It is expected that accrual can be completed in 24 months. 
Using this dose escalation scheme, the probability of escalating to the next dose level, based on 
the true rate of DLT at the current dose, is given by the following table (each group will be 
considered independently of the other):
True rate of DLT 
at a given dose
10%
20%
30%
40%
50%
60%
Probability 
of 
escalating
.91
.71
.49
.31
.17
.08
10.3 POPULATIONS FOR ANALYSES
10.3.1 Evaluable for toxicity 
All patients will be evaluable for toxicity from the time of their first treatment with Selinexor.
10.3.2 Evaluable for response 
Only those patients who have completed radiation treatment will be considered evaluable for 
response. 
10.4 STATISTICAL ANALYSES
10.4.1 General Approach
This is a phase I single arm dose escalation study of Selinexor in combination of radiation and 
temozolomide for patients with newly diagnosed Glioblastoma. Cohorts of 3-6 patients are 
evaluated at each dose level. The dose level on which 2 patients experience unacceptable toxicity 
is considered to have exceeded the MTD. The next lower dose level on which no more than 1/6 
patients experience unacceptable toxicity is considered the MTD for this study.
10.4.2 Analysis of the Primary Endpoints
The primary endpoint will be to define the MTD of this approach.
10.4.3 Analysis of the Secondary and Exploratory Endpoint(s)
•
Define the dose-limiting toxicities of Selinexor in combination with external beam 
radiation therapy (RT) and temozolomide in patients with newly diagnosed with 
glioblastoma or gliosarcoma. DLT’s will be reported descriptively.
•
Determine progression-free survival and overall survival. Time to progression will be 
determined by the interval from initiation of treatment on protocol to progression as 
per RANO criteria or death due to disease progression. For patients without 
progression, time to progression will be censored at last assessment date per RANO 
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treatment on protocol to date of death due to any cause. For patients alive as of last 
follow-up, time to death will be censored at last contact date.
10.4.4 Safety Analyses
Adverse events will be coded as per the CTCAE v5.0.  Each AE will be coded once for each patient 
based on the maximum severity during the assessment period.  The relationship of AEs to study 
intervention will be recorded in addition to the onset date, end date, severity, expectedness, and 
outcome.  
10.4.5 Planned Interim Analyses
The primary endpoint will be defined for the entire cohort and no planned interim analyses will 
be performed.
10.4.6 Sub-Group Analyses
The primary endpoint is based on toxicity at a dose level. Only 3-6 patients will be included per 
dose level except for the expansion cohort. Thus, it is not feasible to include sub-group analyses.
10.4.7 Tabulation of Individual Participant Data
Individual participant data will not be tabulated.
10.4.8 Exploratory Analyses
•
QOL scores will be summarized at baseline and for each visit. This summarization 
will include the mean, standard deviation, standard error of measurement, effect size, 
median, minimum, and maximum. Changes from baseline of health-related quality of 
life questionnaire mean scores will be evaluated. Total and domain mean scores of 
patients will be compared by the response. Analyses to explore clinically meaningful 
change of QOL scores may be performed.
•
PFS and OS will be informally compared with historical outcomes.
11 COLLABORATIVE AGREEMENTS 
11.1 CLINICAL TRIAL AGREEMENT (CTA)
A Clinical Trial Agreement between Karyopharm Therapeutics Inc. and the National Cancer 
Institute for the clinical development of Selinexor (KPT-330) has been executed (CTA # 01119-
18).
12 HUMAN SUBJECTS PROTECTIONS 
12.1 RATIONALE FOR SUBJECT SELECTION
Subjects of both sex and from all racial and ethnic groups are eligible if they meet eligibility 
criteria. To date, there is no information that suggests that differences in radiation or disease 
response would be expected in one group compared with another. Efforts will be made to extend 
accrual to a representative population, but in this preliminary study, a balance must be struck 
between patient safety considerations and limitations on the number of individuals exposed to 
potentially toxic and/or ineffective treatments on one hand and the need to explore ethnic aspects 
of clinical research on the other hand. If differences in outcome that correlate with ethnic identity 

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are noted, accrual may be expanded or a follow-up study may be written to investigate those 
differences more fully.
12.2 PARTICIPATION OF CHILDREN
The biology of gliomas in children is very different than the biology of adult gliomas. As such 
most children are treated in children oncology protocols (COG) protocols through Children’s 
Hospital. This protocol should not compete with the excellent work being done at Children’s 
Hospital and is thus aimed at treating adult patients.
12.3 PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT
Adults unable to give consent are eligible to enroll in and remain on the protocol should capacity 
be lost during the study as the incidence of cognitive incapacitation in the glioma population is 
high. Excluding them would significantly impact enrollment and our ability to meet study 
objectives.  All subjects able to provide consent at the time of enrollment will be offered the 
opportunity to fill in their wishes for research and care, and assign a substitute decision maker on 
the “NIH Advance Directive for Health Care and Medical Research Participation” form so that 
another person can make decisions about their medical care in the event that they become 
incapacitated or cognitively impaired during the course of the study. Note: The PI or AI will 
contact the NIH Ability to Consent Assessment Team (ACAT) for evaluation as needed for the 
following: an independent assessment of whether an individual has the capacity to provide 
consent; assistance in identifying and assessing an appropriate surrogate when indicated; and/or 
an assessment of the capacity to appoint a surrogate. 
Please see section 12.5.1 for consent procedure.
12.4 RISK/BENEFIT ASSESSMENT
12.4.1 Known Potential Risks
12.4.1.1 Risks from Selinexor
The primary risk from this study is increased toxicity from selinexor (14.1.2). 
12.4.1.2 Risks of Temozolomide
Refer to package insert.
12.4.1.3 Risks from Radiation
During participation in this research study, patients will be exposed to 60 Gy from radiation 
therapy and a much smaller amount of radiation from a CT scan used for treatment planning.  
12.4.1.4 Risks from CT Imaging Contrast Agent
Itching, hives or headaches are possible risks associated with contrast agents that may be used 
during CT imaging. Symptoms of a more serious allergic reaction include shortness of breath 
and swelling of the throat or other parts of the body. Very rarely, the contrast agents used in CT 
can cause kidney problems for certain patients, such as those with impaired kidney function.

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12.4.1.5 Risk from MRI scans
Participants are at risk for injury from the MRI magnet if they have metal in their body. There is 
a possibility that participants may experience claustrophobia. There are risks of back discomfort 
related to lying in the scanner. 
12.4.1.6 Risks from MRI Gadolinium Based Contrast Agent (GBCAs)
The most common side effects from MRI contrast (gadolinium) include injection site pain, 
nausea, itching, rash, headaches and dizziness. Serious but rare side effects such as gadolinium 
toxicity and nephrogenic systemic fibrosis, or NSF, are most often seen in patients with severe 
kidney problems.
12.4.1.7 Risks of Blood draws
Side effects of blood draws include pain and bruising in the area where the needle was placed, 
lightheadedness, and rarely, fainting. When large amounts of blood are collected, low red blood 
cell count (anemia) can develop. Up to 31 mL will be drawn during screening and/or baseline 
and up to 10 mL during follow-up.
12.4.1.8 Risks of Questionnaires
Questionnaires may contain questions that are sensitive in nature. The patients are asked to only  
answer questions they are comfortable with.
12.4.2 Known Potential Benefits
The potential benefits from this therapy are disease stabilization and delay or reduction of 
symptoms caused by the cancer, predominantly neurological impairment.
12.4.3 Assessment of Potential Risks and Benefits
A number of clinically appropriate strategies to minimize risks to patients have been built into 
the protocol through the means of inclusion/exclusion criteria, monitoring strategies, and 
management guidelines. The protocol provides for detailed and careful monitoring of all patients 
to assess toxicity. The potential benefit to a patient that participates in this study is better control 
of their tumor growth which may or may not have a favorable impact on symptoms and/or 
survival.
Overall, the potential benefit of the study drug combination and radiation in subjects with newly 
diagnosed glioblastoma and gliosarcoma outweigh the risks. This assessment applies for subjects 
able and unable to provide consent. 
12.5 CONSENT PROCESS AND DOCUMENTATION
The informed consent document will be provided as a physical or electronic document to the 
participant or consent designee as applicable for review prior to consenting.  A designated study 
investigator will carefully explain the procedures and tests involved in this study, and the 
associated risks, discomforts and benefits. In order to minimize potential coercion, as much time 
as is needed to review the document will be given, including an opportunity to discuss it with 
friends, family members and/or other advisors, and to ask questions of any designated study 
investigator. A signed informed consent document will be obtained prior to entry onto the study.
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms used in compliance with 

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policy, including HRPP Policy 303) per discretion of the designated study investigator and with 
the agreement of the participant/consent designee(s).  Whether in person or remote, the privacy 
of the subject will be maintained. Consenting investigators (and participant/consent designee, 
when in person) will be located in a private area (e.g., clinic consult room). When consent is 
conducted remotely, the participant/consent designee will be informed of the private nature of 
the discussion and will be encouraged to relocate to a more private setting if needed.  
Consent will be documented with required signatures on the physical document (which includes 
the printout of an electronic document sent to participant) or as described below, with a manual 
(non-electronic) signature on the electronic document.  When required, witness signature will be 
obtained similarly as described for the investigator and participant. 
Manual (non-electronic) signature on electronic document:
When a manual signature on an electronic document is used for the documentation of consent at 
the NIH Clinical Center, this study will use the following to obtain the required signatures:
•
Adobe platform (which is not 21 CFR Part 11 compliant); or,  
•
iMedConsent platform (which is 21 CFR Part 11 compliant)
During the consent process, participants and investigators will view individual copies of the 
approved consent document on screens at their respective locations (if remote consent); the same 
screen may be used when in the same location, but is not required.  
Both the investigator and the participant will sign the document using a finger, stylus or mouse. 
Note: Refer to the CCR SOP PM-2, Obtaining and Documenting the Informed Consent Process 
for additional information (e.g., verification of participant identity when obtaining consent 
remotely) found at: https://nih.sharepoint.com/sites/NCI-CCR-OCD-
Communications/SitePages/OEC-Administrative---Clinical-Research-(ADCR).aspx?Mode=Edit.
12.5.1 Consent Process for Adults Who Lack Capacity to Consent to Research Participation
For participants addressed in section 12.3, an LAR will be identified consistent with Policy 403 
and informed consent obtained from the LAR, as described in Section 12.5. 
13 REGULATORY AND OPERATIONAL CONSIDERATIONS
13.1 STUDY DISCONTINUATION AND CLOSURE
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to investigator,  the 
Investigational New Drug (IND) sponsor and regulatory authorities.  If the study is prematurely 
terminated or suspended, the Principal Investigator (PI) will promptly inform study participants, 
the Institutional Review Board (IRB), and sponsor and will provide the reason(s) for the 
termination or suspension.  Study participants will be contacted, as applicable, and be informed 
of changes to study visit schedule.
Circumstances that may warrant termination or suspension include, but are not limited to:
•
Determination of unexpected, significant, or unacceptable risk to participants
•
Demonstration of efficacy that would warrant stopping   

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•
Insufficient compliance to protocol requirements
•
Data that are not sufficiently complete and/or evaluable
•
Determination that the primary endpoint has been met
•
Determination of futility
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA).
13.2 QUALITY ASSURANCE AND QUALITY CONTROL
The clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.  An individualized quality management 
plan will be developed to describe a site’s quality management.
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution.
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical trial is conducted and data are generated and biological specimens are collected, 
documented (recorded), and reported in compliance with the protocol, International Council for 
Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., 
Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities.
13.3 CONFLICT OF INTEREST POLICY
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be 
required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial.  The study leadership in conjunction with the NIH has 
established policies and procedures for all study group members to disclose all conflicts of 
interest and will establish a mechanism for the management of all reported dualities of interest.
13.4 CONFIDENTIALITY AND PRIVACY
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s). This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible.

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The study monitor, other authorized representatives of the sponsor, representatives of the 
Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical 
records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records.
The study participant’s contact information will be securely stored at the/each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor requirements.
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be stored at the NCI CCR. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems 
used by the clinical site(s) and by  NCI CCR research staff will be secured and password 
protected. At the end of the study, all study databases will be archived at the NIH.
To further protect the privacy of study participants, a Certificate of Confidentiality has been 
issued by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or 
local level. By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help achieve 
the research objectives and promote participation in studies by helping assure confidentiality and 
privacy to participants.
14 PHARMACEUTICAL AND DEVICE INFORMATION
14.1 SELINEXOR (KPT-330) (IND # 144383) 
14.1.1 Source/Acquisition and Accountability 
Selinexor will be supplied by Karyopharm Therapeutics and delivered directly to the NIH 
pharmacy. Selinexor (KPT-330) is a small molecule, oral, first-in-class, potent selective inhibitor 
of nuclear export (SINE) compound. The NIH pharmacy will be in charge of storing, dispensing 
and disposing/returning the study drug.
14.1.2 Toxicity 
14.1.2.1 Very common side effects (≥10%) 
In 100 people receiving selinexor more than 10 people may have:
•
Nausea
•
Vomiting
•
Diarrhea
•
Weight loss
•
Decreased appetite
•
Low sodium which may increase the risk of seizures

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•
Dehydration
•
Abdominal pain
•
Blurred vision
•
Low platelets in the blood (thrombocytopenia) – which may increase the risk of bleeding
•
Decrease in red blood cells (anemia) causing fatigue
•
Decrease in neutrophils (a type of white blood cell that helps fight infections)
•
Decrease in white blood cells (leukopenia), which may increase the risk of infection
•
Dysgeusia – change in taste
•
Dizziness
•
Constipation
•
Shortness of breath
•
Fatigue and asthenia -- loss of energy; weakness
•
Cough
•
Fever
•
Headache
•
Difficulty falling asleep
•
Pneumonia
•
Low potassium which may cause weakness, muscle cramps and spasms
•
Peripheral edema - swelling in the extremities due to accumulation of fluid, usually in the 
legs
•
High blood sugar which may cause fatigue, increased thirst/hunger, frequent urination, 
weight loss, numbness and tingling in the hands and feet. 
14.1.2.2 Common side effects (≥1-10%)
In 100 people receiving selinexor about 1 to 10 people may have:
•
Rash
•
Eye disorders including cataract (new or worsened), dry eye, visual impairment, seeing 
flashes of light. 
•
Night sweats
•
Dry mouth
•
Stomatitis – a condition that causes painful swelling and sores inside the mouth
•
Dyspepsia – indigestion
•
Chills
•
Hypotension – low blood pressure
•
Hypertension
•
Tachycardia – fast heart rate
•
Nosebleed
•
Contusion (bruise due to body injuries such as fall)
•
Electrolyte disturbances including: 
•
Low phosphate which may cause muscle weakness and fatigue
•
Low magnesium which may cause muscle twitches and cramps
•
Low calcium which may cause numbness and tingling in the hands/feet/face, muscle 
stiffness and cramps

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•
High potassium which may cause muscle weakness, palpitations, or irregular heartbeats 
and chest pain. 
•
Low albumin-a specific type of protein in blood (which may cause swelling especially of 
the hands/feet, weakness, or exhaustion)
•
Peripheral neuropathy - weakness, numbness and pain from never damage, usually in the 
hands and feet
•
Decrease in lymphocytes – a specific type of white blood cell that are part of your 
immune system
•
Increase of creatinine in the blood due to a reduction in kidney function, often related to 
dehydration
•
Elevated liver enzymes, which indicates destruction of the liver cells, including alanine 
aminotransferase increased, aspartate aminotransferase increased, blood alkaline 
phosphatase increased. 
•
Elevated pancreatic enzymes including high amylase and high lipase
•
Muscle weakness
•
Febrile neutropenia – fever in the absence of a normal white blood cell response that may 
mean you have an infection
•
Urinary tract infection
•
Pain in the joints and muscles
•
Malaise (a general feeling of being ill or bodily weakness)
•
Muscle spasms 
•
Gait disturbance
•
Hair loss
•
Itching
•
Depression
•
Syncope – fainting
•
Sepsis (including septic shock) – potentially life-threatening complication of an infection
•
Cognitive disorder- brain disorder in which thinking abilities are  impaired.
•
Mental status changes including confusion
14.1.2.3 Uncommon side effects (>0.1-1%)
In 1,000 people receiving selinexor about 1 to 10 people may have:
•
Tumor lysis syndrome – potentially a life-threatening side effect caused by the rapid 
breakdown of tumor cells and may cause irregular heartbeat, kidney failure or abnormal 
blood test results which included elevated uric acid level, elevated serum potassium and 
phosphorous levels, and a decreased calcium level. 
•
Gastroenteritis (stomach flu)
14.1.2.4 Rare side effects (>0.01-0.1%)
In 10,000 people receiving selinexor about 1 to 10 people may have:
•
Acute cerebellar syndrome – symptoms can include a sudden loss of coordination, 
balance, or slurred speech

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14.1.2.5 Serious adverse effects (≥3 cases reported as related by the Principal Investigator)
•
Cardiac failure
•
Multiple organ dysfunction syndrome
•
Lung infection
•
Bronchitis – infection of the tubes that carry air to and from lungs
•
Acute kidney injury
•
Bacteremia – bacterial infection in the blood
•
Delirium – state of acute confusion
•
Encephalopathy – brain disease, damage, or malfunction, which can present different    
symptoms that range from mild, such as memory loss or subtle personality changes, to 
severe, such as dementia, seizures, or coma.
•
General physical health deterioration
•
Pulmonary embolism – pulmonary embolism occurs when a clump of material, most often 
a blood clot, gets wedged into an artery in your lungs. 
•
Hypoxia – an absence of oxygen supply at the tissue level
14.1.3 Formulation and preparation 
The Selinexor drug substance has a molecular formula of C17H11F6N7O and a molecular 
weight of 443.31. Selinexor is supplied as 20 mg tablets.
14.1.3.1 Chemical Structure of Selinexor
14.1.4 Stability and Storage 
Selinexor will be supplied in clear blister strips composed of either: PVC/PE/PCTFE clear film 
blister with an aluminum foil lidding, or aluminum foil paper lidding . Shipping temperature will 
be 2-30ºC. 
•
Do not store Selinexor above 30°C. 
•
Do not freeze Selinexor. 
14.1.5 Administration procedures
Route of administration is oral.

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14.1.6 Incompatibilities: None known
14.2 TEMOZOLOMIDE (IND # 144383)
Refer to the package insert for toxicities, formulation and preparation, stability and storage and 
incompatibility information.
14.2.1 Source
Commercial temozolomide will be purchased by NIH CC Pharmacy.
14.2.2 Administration procedures 
Please refer to section 3.2.2 for details.
14.3 RADIATION
14.3.1 Source
The radiation device is an FDA cleared commercial device located in the NIH Clinical Center.  
The device will be used/investigated in accordance with labeling and therefore will be IDE 
exempt under 812.2 (c) – category 1.
14.3.2 Toxicity to brain
This list represents the effects of radiation that have been noted for patients to this area of the 
body.  Each person may have different reactions.  It is not possible, therefore, to predict any 
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Reactions can occur during shortly after, or long after the treatment courses and may 
include, but are not necessarily limited to the following:
14.3.3 Administration Procedures
Refer to section 3.6.
DURING OR SHORTLY AFTER TREATMENT 
COURSE
AFTER TREATMENT COURSE
(MONTHS TO YEARS)
COMMON
COMMON
Skin redness and irritation in area treated
Scalp discoloration and thickening
Hair loss in area treated, including eyebrows 
Mild decrease in memory or ability to think
Tiredness
Worsening of neurologic symptoms present prior to 
radiation
Permanent thinning or loss of hair in treated 
area including eyebrows
UNCOMMON
UNCOMMON
Tiredness, headache, weakness, numbness, or other 
neurologic deficit which may require steroid 
treatment
Nausea, vomiting, weight loss
Increase in seizure activity if already present
Dry eyes
Permanent loss (death) of brain cells
Development of seizures
Severe memory loss 
Cataracts in eyes
Hearing loss
Dry eyes
RARE
RARE
Decreased blood cell count
Excessive need of sleep
Death of brain cells causing swelling in the 
brain and requiring long term steroid treatment, 
hospitalization, or/or surgery
OTHER
Loss or decrease of vision
Change in hormone levels from the pituitary
EXTREMELY RARE
Development of new tumors in scalp, skull or 
brain
Difficulty with control of water balance, thirst, 
loss of salts from body
Loss of function specific to the area affected 
such as: vision, sensation, memory, judgement, 
motor skills
Damage to retina causing blindness 
Damage to blood vessels leading to stroke or 
may be fatal. 

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RTOG 7401/ECOG 1374 with long-term follow-up: a joint study of the Radiation 
Therapy Oncology Group and the Eastern Cooperative Oncology Group, vol. 6; 
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Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJB, Janzer RC, Ludwin 
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Leucine-Rich Nuclear Export Signals. Cell 1997, 90(6):1051-1060.
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Landesman Y, Eisfeld AK, Gabrail NY et al: Preclinical and clinical efficacy of 
XPO1/CRM1 inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias. 
Blood 2013, 122(17):3034-3044.
18.
Tai YT, Landesman Y, Acharya C, Calle Y, Zhong MY, Cea M, Tannenbaum D, 
Cagnetta A, Reagan M, Munshi AA et al: CRM1 inhibition induces tumor cell 
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Salas Fragomeni RA, Chung HW, Landesman Y, Senapedis W, Saint-Martin JR, Tsao H, 
Flaherty KT, Shacham S, Kauffman M, Cusack JC: CRM1 and BRAF inhibition 
synergize and induce tumor regression in BRAF-mutant melanoma. Mol Cancer 
Ther 2013, 12(7):1171-1179.
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Wahba A, J ON, Rath BH, Camphausen K, Tofilon PJ: The XPO1 inhibitor Selinexor 
enhances the radiosensitivity of glioblastoma cells grown in vitro and in vivo The 
XPO1 inhibitor Selinexor enhances the radiosensitivity of glioblastoma cells grown 
in vitro and in vivo Mol. Can. Ther. 17(8): 1717-1726, 2018.
21.
Ferreiro-Neira I, Torres NE, Liesenfeld LF, Chan CH, Penson T, Landesman Y, 
Senapedis W, Shacham S, Hong TS, Cusack JC: XPO1 Inhibition Enhances Radiation 
Response in Preclinical Models of Rectal Cancer. Clin Cancer Res 2016, 22(7):1663-
1673.
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Tabe Y, Kojima K, Yamamoto S, Sekihara K, Matsushita H, Davis RE, Wang Z, Ma W, 
Ishizawa J, Kazuno S et al: Ribosomal Biogenesis and Translational Flux Inhibition 

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by the Selective Inhibitor of Nuclear Export (SINE) XPO1 Antagonist KPT-185. 
PLoS One 2015, 10(9):e0137210.
23.
Mau-Sørensen M, Plotkin SR, Wen PY, Kung AL, Lassen UN, Saint-Martin J-R, Wright 
G, Chudnovsky A, Ellis J, Friedlander S et al: A phase 2 study on efficacy, safety and 
intratumoral pharmacokinetics of oral selinexor (KPT-330) in patients with 
recurrent glioblastoma (GBM). 2016, 34(15_suppl):2077-2077.
24.
Lassman AB, Bent MJ VD, Wen PY, Walenkamp A, Plotkin S, Kung A, Gardner H, 
Shacham S, Chudnovsky A, Mau-Sorensen PM: OS07.5 Interim analysis data from 
Phase 2 study on efficacy, safety & intratumoral pharmacokinetics of oral Selinexor 
(KPT-330) in patients with recurrent glioblastoma (GBM). Neuro-Oncology 2017, 
19(Suppl 3):iii14-iii14.
25.
Ellingson BM, Wen PY, Cloughesy TF: Modified Criteria for Radiographic Response 
Assessment in Glioblastoma Clinical Trials. Neurotherapeutics : the journal of the 
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16 APPENDICES
16.1 APPENDIX A: PERFORMANCE STATUS CRITERIA
Karnofsky Performance Scale
Percent
Description
100
Normal, no complaints, no evidence of disease.
90
Able to carry on normal activity; minor signs or symptoms of disease.
80
Normal activity with effort; some signs or symptoms of disease.
70
Cares for self, unable to carry on normal activity or to do active work.
60
Requires occasional assistance, but is able to care for most of his/her 
needs.
50
Requires considerable assistance and frequent medical care.
40
Disabled, requires special care and assistance.
30
Severely disabled, hospitalization indicated. Death not imminent.
20
Very sick, hospitalization indicated. Death not imminent.
10
Moribund, fatal processes progressing rapidly.
0
Dead.

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16.2 APPENDIX B: RTOG RADIATION MORBIDITY SCORING CRITERIA

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16.3 APPENDIX C: RTOG LATE RADIATION MORBIDITY SCORING CRITERIA

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16.4 APPENDIX D: MD ANDERSON SYMPTOM INVENTORY FOR BRAIN TUMORS (MDASI-BT)
 

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16.5 APPENDIX E:  NEURO-QOL ITEM BANK V2.0

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16.6 APPENDIX F: EMOTIONAL DISTRESS -DEPRESSION-SHORT FORM 8A

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16.7 APPENDIX G: PRO-CTCAE

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16.8 APPENDIX H: ORAL MEDICATION DIARY FOR SELINEXOR – WEEKLY
Today’s Date ________________________________ 
_________
Patient Name_______________________________ (initials acceptable for patient’s name)
Patient Study ID ___________________ 
Please bring your pill bottle and this form to your physician when you go for your next appointment. 
This is required for study compliance. 
INSTRUCTIONS TO THE PATIENT: 
1. Complete one form for each cycle (14 days). 
2. You will take selinexor tablets on the second day of radiation and by mouth once a week. 
Please ask your doctor what dose you will be getting and how often you will get it.
3. Record the date, the number of tablets you took, and when you took them. 
4. If you have any comments or notice any side effects, please record them in the Comments column. 
Selinexor
Date
Week/Day
Comments 
W1 D2 
W2 D2 
W3 D2 
W4 D2 
W5 D2 
 
Patient’s Signature: __________________________________ Date: _____________________ 
Study Team will complete this section: 
1.
Date patient started protocol treatment_____________________
2.
Date patient was removed from study ______________________ 
3.
Patient’s planned daily dose______________________________ 
4.
Total number of pills taken this month _____________________ 
Physician/Nurse Practitioner/Nurse’s Signature: ______________________  

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16.9 APPENDIX I: ORAL MEDICATION DIARY FOR SELINEXOR – TWICE WEEKLY
Today’s Date ________________________________ 
_________
Patient Name_______________________________ (initials acceptable for patient’s name)
Patient Study ID ___________________ 
Please bring your pill bottle and this form to your physician when you go for your next appointment. This 
is required for study compliance. 
INSTRUCTIONS TO THE PATIENT: 
1. Complete one form for each cycle (14 days). 
2. You will take selinexor tablets on the first and fourth day of radiation. Please ask your doctor what 
dose you will be getting and how often you will get it.
3. Record the date, the number of tablets you took, and when you took them. 
4. If you have any comments or notice any side effects, please record them in the Comments column. 
Date
Week/Day
Selinexor
Comments 
W1 D1
W1 D4 
W2 D1
W2 D4
W3 D1
W3 D4 
W4 D1
W4 D4 
W5 D1
W5 D4 
W6 D1
(only take if you are in the third group of the study)
W6 D4 
(only take if you are in the third group of the study)
 
Patient’s Signature: _________________________________ Date: _____________________ 
Study Team will complete this section: 
5.
Date patient started protocol treatment______________________
6.
Date patient was removed from study ______________________ 
7.
Patient’s planned daily dose______________________________ 
8.
Total number of pills taken this month _____________________ 
Physician/Nurse Practitioner/Nurse’s Signature: _______________________