Clinical trial NCT03180528
Conditions: Skin Basal Cell Carcinoma
Sponsor: Kavita Sarin
Start date: 2018-07-07; Completion date: 2020-12-31
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase 2 trial studies how well remetinostat works in treating patients with skin basal cell cancer. Remetinostat may slow the growth of basal cell cancer cells.

Detailed description:
PRIMARY OBJECTIVES:

I. Overall response rate of basal cell carcinoma (BCC) in subjects at 6 weeks.

SECONDARY OBJECTIVES:

I. Suppression of GLI1 (glioma-associated oncogene) expression in treated BCCs as compared with baseline.

II. Safety assessment of Remetinostat after 6 weeks of topical treatment.

OUTLINE:

Tumors receive Remetinostat topically three times per day (TID) for 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for at least 4 weeks.

Arms: arm 1: Patients receive topical remetinostat 1% gel applied TID directly to the lesion, for 6 weeks in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Remetinostat
Intervention descriptions: intervention 1: Applied topically under bandage occlusion

Protocol documents:
Prot_SAP_001.pdf: 
CONFIDENTIAL:  
IRB-40947  
Page 1 of 51 
 2 October 2020  
A Phase 2 Open-label, Single-arm Trial to Investigate the 
Efficacy and Safety of Topical Remetinostat Gel as 
Neoadjuvant Therapy in Patients Undergoing Surgical 
Resection of Basal Cell Carcinoma (BCC)  
Coordinating Center 
Stanford Cancer Institute 
Medical Dermatology 
450 Broadway St  
Pavilion C, , MC xxxx 
Redwood City, CA  xxxxxxxxx 
Protocol Director  
Kavita Y Sarin, MD, PhD 
Stanford Cancer Institute 
Medical Dermatology 
450 Broadway St  
Pavilion C, xxxxxxxx MC xxxx 
Redwood City, CA  xxxxxx 
Phone xxx-xxx-xxxx;  Fax xxx-xxx-xxxx 
ksarin@stanford.edu  
Sub-Investigators 
 
Anthony Oro, MD, PhD 
 
 
Stanford, California  94305 
 
Jean Yuh Tang, MD, PhD 
450 Broadway St., 
MC 5334 
Redwood City, CA 
 
James M. Kilgour, MD 
455 Broadway St. 
Redwood City, CA 94063 
 
Biostatistician 
Shufeng Li MS 
780 Welch Road, 
CJ220D 
Palo Alto, CA 
 94304-5779 
 
Study Coordinator 
Irene Bailey 
450 Broadway St. 
Pavilion C, 2nd Floor, 
MC 5334 
Redwood City, CA 
 
 
Version Date:  2 October 2020  
SRC approval date:  18 October 2018 
IRB-40947  
SKIN0037 
NCT03180528 
IND 134521 


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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ................................................................................................. 4 
SCHEMA ......................................................................................................................... 5 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .......................................... 6 
1. 
OBJECTIVES ........................................................................................................ 7 
1.1. PRIMARY OBJECTIVE .............................................................................................. 7 
1.2. SECONDARY OBJECTIVES ....................................................................................... 7 
2. 
BACKGROUND..................................................................................................... 7 
2.1 STUDY DISEASE .................................................................................................... 7 
2.2 STUDY AGENT ....................................................................................................... 8 
2.3 RATIONALE ......................................................................................................... 11 
2.4 STUDY DESIGN .................................................................................................... 11 
2.5 CORRELATIVE STUDIES BACKGROUND .................................................................. 12 
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES ................... 12 
3.1 INCLUSION CRITERIA ............................................................................................ 12 
3.2 EXCLUSION CRITERIA ........................................................................................... 12 
3.3 INFORMED CONSENT PROCESS ............................................................................ 13 
3.4 RANDOMIZATION PROCEDURES ............................................................................. 13 
3.5 STUDY TIMELINE .................................................................................................. 14 
4. 
TREATMENT PLAN ............................................................................................ 14 
4.1 GENERAL CONCOMITANT MEDICATION AND SUPPORTIVE CARE GUIDELINES ............ 15 
4.2 CRITERIA FOR REMOVAL FROM STUDY .................................................................. 16 
4.3 ALTERNATIVES .................................................................................................... 17 
5. 
INVESTIGATIONAL AGENT INFORMATION .................................................... 17 
5.1 INVESTIGATIONAL AGENT ..................................................................................... 17 
5.2 AVAILABILITY ....................................................................................................... 17 
5.3 AGENT ORDERING ............................................................................................... 17 
5.4 STORAGE CONDITIONS ......................................................................................... 17 
5.5 AGENT ACCOUNTABILITY ...................................................................................... 18 
6. 
DOSE MODIFICATIONS ..................................................................................... 18 
6.1. DOSE MODIFICATIONS DUE TO TOXICITY AND STOPPING CRITERIA ........................... 18 
7. 
ADVERSE EVENTS AND REPORTING PROCEDURES ................................... 19 
7.1 POTENTIAL ADVERSE EVENTS .............................................................................. 19 
7.2 ADVERSE EVENT REPORTING ............................................................................... 21 
8. 
EXPLORATIVE / CORRELATIVE / SPECIAL STUDIES .................................... 23 
8.1. INCREASED ACETYLATION OF HDAC SUBSTRATES AS A PD MARKER ...................... 23 
8.2. MEASUREMENT DEFINITION .................................................................................. 23 
8.3. ANALYSIS POPULATION ........................................................................................ 23 
8.4. MEASUREMENT METHODS .................................................................................... 23 
8.5. ANALYSIS PLAN ................................................................................................... 23 
9. 
STUDY CALENDAR ............................................................................................ 24 
10. 
MEASUREMENTS .............................................................................................. 25 
10.1  PRIMARY OUTCOME ............................................................................................. 25 
11. 
REGULATORY CONSIDERATIONS .................................................................. 25 
11.1 INSTITUTIONAL REVIEW OF PROTOCOL .................................................................. 25 
11.2 DATA AND SAFETY MONITORING PLAN .................................................................. 26 


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11.3 DATA MANAGEMENT PLAN .................................................................................... 26 
12. 
STATISTICAL CONSIDERATIONS .................................................................... 26 
12.1 STATISTICAL DESIGN ........................................................................................... 26 
12.2 RANDOMIZATION .................................................................................................. 26 
12.3 INTERIM ANALYSES .............................................................................................. 26 
12.4 DESCRIPTIVE STATISTICS AND EXPLORATORY DATA ANALYSIS ................................ 26 
12.5 PRIMARY ANALYSIS .............................................................................................. 27 
12.6 SECONDARY ANALYSIS......................................................................................... 27 
12.7  SAMPLE SIZE ...................................................................................................... 29 
13. 
REFERENCES .................................................................................................... 30 
APPENDIX A:  PARTICIPANT ELIGIBILITY CHECKLIST .......................................... 31 
APPENDIX B:  STUDY IRB-40947 PARTICIPANT INFORMATION SHEET ............... 33 
APPENDIX C:  STUDY IRB-40947 PARTICIPANT MEDICATION  
                APPLICATION DIARY ......................................................................... 33 
APPENDIX D:  SERIOUS ADVERSE EVENT REPORT FORM (DIAMOND) .............. 33 
 


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PROTOCOL SYNOPSIS 
TITLE 
A Phase 2 Open-label, Single-arm Trial of the Efficacy of and 
Safety of Topical Remetinostat Gel as Neoadjuvant Therapy 
in Patients with Basal Cell Carcinoma undergoing surgical 
resection 
STUDY PHASE 
Phase 2 
INDICATION 
Treatment of basal cell carcinoma  
INVESTIGATIONAL 
PRODUCT  
Topical remetinostat gel 1% 
PRIMARY 
OBJECTIVE 
• 
To determine if topical remetinostat gel will decrease 
BCC size by at least 30% following 6 weeks’ TID treatment   
• 
To determine the overall response rate (ORR) of BCC 
tumors after 6 weeks of treatment TID 
SECONDARY 
OBJECTIVE 
1. To determine if topical remetinostat gel 1% will decrease 
HH biomarker GLI1 from baseline levels following 6 weeks’ 
TID treatment: 
2. To assess the safety of remetinostat gel 1% when applied 
topically TID under occlusion for 6 weeks as follows: 
• Incidence, type, and severity of adverse events (AEs)  
• Incidence and nature of serious adverse events (SAEs)  
• Incidence of AEs leading to remetinostat discontinuation or 
interruption  
• Adherence to the treatment, measured by number of 
patients discontinuing the treatment (for any reason) and 
treatment interruptions  
EXPLORATORY 
STUDIES 
To assess local pharmacodynamics (PD) effects of 
remetinostat by immunohistochemistry (IHC) on histone 
acetylation in BCC biopsy sections    
TREATMENT 
SUMMARY 
Apply topical remetinostat gel 1% 3 times daily (TID) under 
bandage occlusion for 6 weeks 
SAMPLE SIZE  
30 BCC tumors treated per-protocol 
STATISTICAL 
CONSIDERATIONS 
Overall response rate of BCC tumors (Primary Objective and 
Primary Outcome) in subjects will be defined as at least a 
30% decrease in the diameter of BCC lesion.  With a planned 
analysis on 30 per-protocol BCCs, this study would provide 
91% power to reject an ORR of 15% if the true ORR is 
40% or better, at one-sided alpha level of 0.05 with at least 
9 responders.  
For the Secondary Objective 1 (HH biomarker GLI1), at least 
10 pre- and post-treatment (6 weeks) BCC tumor pairs will be 
analyzed.  With a sample size of 10 paired BCCs, this study 


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will have greater than 98% power to detect a 43% (SD:  30%) 
decrease in GLI1 mRNA levels at 2-sided alpha level 0.05. 
For Secondary Objective 2, toxicities will be graded according 
to the National Cancer Institute CTCAE v5.0.  
For the Exploratory Studies, PD endpoints will include, but are 
not limited to, an assessment of histone acetylation.  The 
analysis will be performed on BCC biopsy sections using IHC.   
SCHEMA 
  


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
ADL 
Activities of daily living 
AE 
Adverse event 
BCC 
Basal cell cancer / carcinoma 
CBC 
Complete blood count 
CI 
Confidence interval 
CR 
Complete response 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTCL 
Cutaneous T-cell lymphoma 
DLT 
Dose-limiting toxicity 
DSMC 
Data Safety Monitoring Committee 
EKG 
Electrocardiogram 
GLI1 
Glioma-associated oncogene 1 
Hgb 
Hemoglobin 
HDAC 
Histone deacetylase  
HH 
Hedgehog 
IRB 
Institutional Review Board 
IV 
Intravenous 
LLN 
Lower limit of normal  
OS 
Overall survival  
PLT 
Platelet 
PD 
Progressive disease 
PFS 
Progression-free survival  
PR 
Partial response 
PTCH1 
Protein patched homolog 1 
QD 
Once daily 
RECIST 
Response evaluation criteria in solid tumors 
RR 
Response rate 
SAE 
Serious adverse event 
SD 
Stable disease 
SMO 
Smoothened 
TID 
Three times daily 
ULN 
Upper limit of normal 
UNK 
Unknown 
WBC 
White blood cell 


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1. 
OBJECTIVES 
1.1. 
Primary Objective 
 
Overall response rate of BCC in subjects defined by at least a 30% decrease in BCC tumor 
diameter at end of study measurement as compared with baseline measurements.  
RECIST v1,1 criteria can no longer be used as BCC patients with BCCs under 10 mm will be 
enrolled.  Therefore, the threshold for positive response will be at least 30% decrease in tumor 
size. 
1.2. 
Secondary Objectives 
 
• 
Suppression of GLI1 expression in treated BCC as compared with baseline.  
• 
Safety assessment of remetinostat after 6 weeks of topical treatment will be evaluated 
as follows: 
o Incidence, type, and severity of adverse events (AEs)  
o Incidence and nature of serious adverse events (SAEs)  
o Incidence of AEs leading to remetinostat discontinuation or interruption  
o Adherence to the treatment, measured by number of patients discontinuing the 
treatment (for any reason) and treatment interruptions  
2. 
BACKGROUND 
2.1 
Study Disease 
Basal cell carcinomas (BCCs) are the most common human cancer, affecting approximately 
750,000 Americans per year (Epstein, 2008).  Based on rapidly rising tumor incidence rates, it is 
estimated that almost 1 in 3 Caucasians born in the United States after 1994 will develop a BCC 
during their lifetime (Miller and Weinstock, 1994).  Like that of other skin cancers, BCC risk is 
correlated inversely with the degree of skin pigmentation and positively with exposure to 
ultraviolet (UV) or ionizing radiation (IR).  Patients affected by the basal cell nevus syndrome 
(BCNS, Gorlin syndrome, nevoid basal cell carcinoma syndrome; OMIM #109400), a rare 
autosomal dominant inherited disorder, have a dramatically increased risk of developing BCCs 
(developing tens to hundreds to thousands of BCCs) and as well as an increased risk of 
developing certain extra cutaneous tumors (eg, medulloblastomas and rhabdomyosarcomas) 
(Gorlin, 1987).  Patients with BCNS inherit a defective copy of the tumor suppressor gene, 
PTCH1, which acts as a primary inhibitor of the hedgehog (HH) signaling pathway 
(Hahn, et al, 1996; Johnson, et al, 1996).  PTCH1 gene mutations and loss of the remaining 
wild-type allele also have been identified in sporadic basal cell carcinomas and 
medulloblastomas, suggesting a common genetic basis for the sporadic and 
syndrome-associated cancers (Hahn, et al, 1996; Johnson, et al, 1996; Xie, et al, 1997; 
Raffel, et al, 1997;  Ling, et al, 2001).  Mutations in SMO, the downstream molecule that is the 
target of PTCH1 inhibition, occur in approximately 10% of sporadic BCCs with resultant 
resistance of SMO protein to inhibition by normal PTCH1 protein (Xie, et al, 1998; 
Reiffenberger, et al, 1998).  Essentially all BCCs, whether or not associated with identifiable 
mutations of PTCH1 or of SMO, have enhanced HH signaling.  BCCs generally are treated by 
local excision, which in many cases is scarring and disfiguring.  Currently there is no reliable 
medical (non-surgical) therapy for treatment of either BCNS-related or sporadic BCCs.  Oral 
retinoid treatment of BCNS patients can reduce the rate of development of BCCs but does so 
only at a dose that usually produces intolerable side effects (Peck, et al, 1988; 
Tangrea, et al, 1992).  The clinical use of SMO antagonists which suppress HH signaling have 
efficacy and are FDA approved for the treatment of BCC providing strong scientific evidence 


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that HH inhibition can be a highly effective approach to chemotherapy and chemoprevention of 
BCC (Tang, et al, 2016). 
2.2 
Study Agent  
Histone deacetylase (HDAC) inhibitors, including vorinostat and romidepsin were approved by 
the US FDA for the treatment of cutaneous T-cell lymphoma (CTCL) (Mann BS, et al, 2007).  
HDAC inhibitors antagonize tumors by altering the expression of oncogenes or tumor 
suppressor, through modulating the level of acetylation/deacetylation of histones and/or 
non-histone proteins such as transcription factors.   
Unpublished data has shown HDAC inhibitors can inhibit the growth of BCC cells and BCC 
tumors in vitro and in vivo.  
HDAC inhibitors can suppress growth of BCC cell lines 
To study the efficacy of HDAC1 inhibition in BCCs in vitro, a murine BCC cell line (ASZ) 
resistant to SMO inhibitors but dependent on GLI1 was treated with increasing doses of 
vorinostat, a pan-HDAC inhibitor, and parthenolide, a HDAC1-depleting compound.  Vorinostat 
treatment resulted in a dose-dependent reduction in HH signaling as assayed by qPCR of GLI1 
mRNA, a canonical target gene of the HH pathway and BCC proliferation (Figure 1).  Similarly, 
results were seen with parthenolide, a specific inhibitor of HDAC1 expression implicating 
HDAC1 as the critical target of HDAC inhibitors for BCC. 
A)
B)
  
C)
 
Figure 1.  A) HH target genes transcripts dose response to vorinostat and parthenolide in ASZ cells with drug IC50 
represented by dotted line (n = 9).  GLI1 transcript measured by quantitative PCR and normalized against HPRT.  
B,C) Relative ASZ cell growth measured by Real Time Glo Reagent following vorinostat (B) and parthenolide 
(C) treatment (n = 3). 


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HDAC inhibitors can suppress growth of BCC tumor allografts 
BCCs allografts, generated from Ptch1+/- K14-Cre-ER2 p53 fl/fl mice were injected 
subcutaneously into NOD/SCID mice as previously described and allowed to engraft for 
3 weeks until a consistent 5 mm palpable tumor was visible.  100 mg/kg of vorinostat 
administered intraperitoneally twice daily in vivo on the BCC allografts resulted in inhibition of 
GLI1 and completely suppressed tumor growth at 14 days compared to a 350% growth in tumor 
volume in the placebo.  Skin and organ toxicity was not observed in mice at these dosages.  
(Figure 2).  Altogether, the preliminary data implicates HDAC inhibitors as a promising new 
candidate therapy for BCC.   
 
Figure 2.  (left) Vorinostat suppresses growth of BCC allografts (blue) as compared to placebo / DMSO 
(black) (right) GLI1 mRNA levels are suppressed by vorinostat in murine tumor allografts. 
HDAC1 has been previously shown to provide a pivotal step in the activation of GLI1 through 
deacetylation at K518 (Canettieri, et al, 2010), suggesting a potential mechanism of action by 
which HDAC1-inhibition can suppress HH signaling and suppress BCC. 
Remetinostat is a novel histone deacetylase inhibitor (HDACi) that was designed with a 
metabolically-labile ester bond so that topical application would produce effective local histone 
deacetylase (HDAC) inhibition in cutaneous lesions while resulting in only negligible systemic 
HDAC inhibition.  Remetinostat is rapidly degraded into primary metabolites SHP-100 and 
methylparaben.  Three studies (an in vitro Franz Diffusion Cell assay; a 28-day study in 
minipigs; and a 90-day study in minipigs) showed that uptake of remetinostat through skin into 
the systemic circulation was minimal.  In both dermal and intravenous (IV) studies in animals, 
remetinostat was metabolized in the blood rapidly to the primary metabolites.  These findings 
suggest that dermal application of remetinostat largely obviates systemic exposure to the HDAC 
inhibitor remetinostat and, consequently, sequelae from systemic inhibition of HDAC.  This 
observation was supported by the fact that in a Phase 1 study in patients with cutaneous T-cell 
lymphoma (CTCL), plasma concentrations of remetinostat were minimal and at or below the 
lower limit of quantitation of the assay indicating minimal systemic exposure.  The lack of 
measurable levels of remetinostat in blood is consistent with the rapid conversion of 
remetinostat to its metabolites. 
Remetinostat has been tested in a battery of safety pharmacology studies.  Remetinostat did 
not affect the functional observational battery (FOB) parameters in rats given IV doses of up 


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100 mg/kg/day, which is equivalent to a dose of approximately 970 mg in a 60-kg human 
subject.  Remetinostat also did not inhibit human ether à-go-go-related gene (hERG) current 
in vitro at concentrations up to approximately 32,000 ng/mL and did not affect cardiovascular 
function in minipigs given IV doses of up to 100 mg/kg, which is equivalent to a dose of 
approximately 5,700 mg in a 60-kg human subject.  Based on the lack of effect observed in 
these studies, it was anticipated that remetinostat would be unlikely to adversely affect nervous 
system or cardiovascular system function when administered topically to humans.  This 
observation has been supported by the clinical data, to date. 
A program of Good Laboratory Practice (GLP)-compliant toxicity studies evaluated the safety of 
multiple doses of remetinostat administered IV to rats and administered topically to minipigs.  
In addition, the genotoxicity of remetinostat and the local tolerance and sensitizing potential of 
remetinostat and placebo gel solutions were assessed.  Remetinostat and placebo gel were 
tolerated, with only excipient-related local irritation when applied topically, and renal 
histopathologic changes not relevant in humans when administered IV.  The 28-day 
No-Observed-Adverse-Effect-Level (NOAEL) for remetinostat administered IV to rats was 
30 mg/kg/day.  When remetinostat gel 1.5% was applied topically in minipigs, the 28-day and 
90-day NOAEL of 150 μg/cm2 of skin yielded a total dose of approximately 6 mg/kg. 
Based on these findings, a phase 1 (SHP-141-001) study was conducted (NCT01433731) in 
18 patients with stage IA-IIA MF-CTCL.  This randomized, double-blind, placebo-controlled 
dose-escalating study was designed to evaluate the safety, pharmacokinetics and 
pharmacodynamics of remetinostat gel administered topically twice-daily up to 28 days in 
patients.  Escalating doses of remetinostat gel, 0.1%, 0.5%, and 1%, were administered BID for 
a maximum of 28 days to 3 cohorts of patients (n = 6 patients per cohort, 
active:placebo ratio 5:1). 
A Phase 2, multicenter, open-label, randomized study (SHP-141-003, NCT02213861) to 
evaluate the efficacy and safety of remetinostat applied topically in 60 patients with stage IA to 
IIA MF-CTCL was completed in September 2016.  Three doses of remetinostat were evaluated 
in three treatment arms (n = 20 per treatment arm, 1:1:1 randomization).  The 3 dosing 
regimens of remetinostat (1% QD, 0.5% BID and 1% BID) were tested in this study for between 
6 to 12 months. 
All doses and schedules of remetinostat were well-tolerated.  There were three CTCAE grade 
≥ 3 remetinostat treatment related AEs, with 2/20 patients discontinuing treatment due to 
remetinostat related AEs, for the highest dose group of 1% gel BID (2/20 and 6/20 for the 
1% gel QD and 0.5% gel BID dose groups respectively).  There were no remetinostat treatment 
related systemic adverse events reported in either clinical study, which is consistent with the 
minimal systemic exposure and very short half-life of remetinostat in human blood. 
A phase 1 study in patients with psoriasis resulted in limited efficacy but the safety profile was 
similar to the MF-CTCL studies; no serious adverse events were seen on this study.   
Remetinostat is not currently approved by FDA for any use, and an Investigational New Drug 
application (IND) is required.  The IND number is IND 134521. 


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2.3 
Rationale 
The severity of BCC burden differs widely among patients from those who develop early BCCs, 
have advanced BCC; or suffer from numerous BCCs lesions.  In the more severely-affected, 
such as those with basal cell nevus syndrome or extensive chronic sun exposure, essentially all 
of their skin appears to be susceptible to the development of BCCs, and their quality of life is 
severely degraded by the need for frequent, repetitive surgical procedures (Bree AF, et al).  
Some patients need to have a dozen or more BCCs treated each year.  These procedures are 
time-consuming and expensive, and they inevitably produce scarring.  Exhortations to avoid 
sunlight have minimal effect on slowing the rate of development of BCCs in these patients.  
Hence the patients currently have an endless vista of surgical procedures in their future, with no 
light at the end of the tunnel.  Other patients may have fewer tumor lesions but they occur in 
cosmetically-disfiguring areas or near functional areas where surgery is not ideal.  
The pivotal molecular abnormality in basal cell carcinoma is constitutive activation of the 
hedgehog (HH) signaling pathway, commonly due to mutational inactivation of the gene 
encoding the tumor suppressor, Patched1 (Ptch1).  Ptch1 is a transmembrane receptor for the 
hedgehog ligand and is the key natural inhibitor of HH signaling.  It accomplishes this by 
preventing signaling by SMO and hence inhibits activation of the transcriptional factor, GLI.  In 
addition to uniform constitutive activation of the HH pathway, human BCCs also frequently have 
mutations in p53.  
All BCCs have up-regulation of HH signaling due to loss of PTCH1 or activation of SMO 
(Epstein, 2008).  SMO inhibitors replace the function of mutant PTCH1 by inhibiting HH 
signaling and have efficacy in treatment of BCCs.  However, after varying duration, patients may 
find the adverse effects of the drug to be intolerable and may stop taking treatment, leading to 
recurrence of BCC.  Therefore, a downstream topical HH inhibitor is likely to be better-tolerated 
because of the expected lack of adverse effects, and inhibition of hedgehog signaling by a 
topical agent is likely to inhibit BCC carcinogenesis.  Therefore, as HDAC inhibitors work further 
downstream to SMO inhibitors to inhibit the HH signaling pathway, it is hope that remetinostat 
may show efficacy without the adverse effects of SMO inhibitors. 
2.4 
Study Design 
For clinicaltrials.gov and Stanford Clinical Trials Directory compliance  
• 
The primary purpose of this study is;  
o 
To determine if 6 weeks of topical remetinostat gel applied TID under occlusion will 
suppress BCC growth 
o 
To determine the overall response rate (ORR) of BCCs after 6 weeks of treatment 
with topical remetinostat gel 1%, as measured by at least 30% decrease in greatest 
diameter.   
• 
Subjects with at least 1 cutaneous BCC will be recruited for this study.   
• 
Subjects will apply remetinostat gel 1% to at least 1 BCC.   
• 
All BCC types, ie, superficial, nodular, micronodular, or morpheaform, are eligible for this 
study. 
• 
There is 1 treatment option:  Topical remetinostat gel 1% applied 3 times daily.   


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• 
The study is a single arm, open label design 
• 
For purposes of ClinicalTrials.gov, there is no secondary outcome.  
2.5 
Correlative Studies Background 
There are no planned correlative studies.   
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES 
3.1 
Inclusion Criteria 
1. Must have at least one cutaneous BCC lesion greater than or equal to 5 mm. BCC 
lesion(s) can be superficial, nodular, micronodular, or morpheaform BCC, but must be 
amenable to surgical resection.  
2. 18 years of age or older. 
3. Must be willing to apply the topical remetinostat 3 times daily for 6 weeks and cover with 
an occlusive bandage. 
4. Negative serum pregnancy test within 14 days prior to the first dose of study therapy for 
women of child-bearing potential, defined as a sexually mature woman who has not 
undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 
consecutive months (ie, who has had menses any time in the preceding 24 consecutive 
months) 
5. Sexually active women of child bearing potential (WCBP) and male patients with a 
female partner of child-bearing potential must agree to use acceptable methods of 
contraception to avoid pregnancy (for example, oral, injectable, or implantable hormonal 
contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; 
or vasectomized partner) before the first dose of study therapy and for 3 months after 
the last dose of study therapy  
6. Has signed and dated the current IRB-approved informed consent document.   
3.2 
Exclusion Criteria 
1. Any large (> 25 mm) BCC lesion.  Patients with large BCC lesion(s) will be referred for 
evaluation for surgical resection.  
2. Inoperable locally-advanced and/or non-cutaneous metastatic BCC.  
3. Taking any medication known to affect HH signaling pathway such as itraconazole.   


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4. Within the past 6 months, has used topical or systemic therapies that might interfere with 
the evaluation of the study medication during the study.  Specifically, these include the 
topical use to the study tumors of:   
o Glucocorticoids  
o Retinoids either systemically or topically at the tumor site (eg, etretinate, isotretinoin, 
tazarotene, tretinoin, adapalene)  
o Alpha-hydroxy acids (eg, glycolic acid, lactic acid) to > 5% of the skin or to the tumor 
site 
o 5-fluorouracil or imiquimod and/or  
o Itraconazole  
5. Has received treatment with systemic chemotherapy or agents known to be inhibitors of 
HH signaling, within 60 days prior to starting study medication. 
6. Currently receiving systemic medications that could affect BCC tumors 
(eg, oral retinoids) or might interact with remetinostat 
7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 
recurrent seizure history or psychiatric illness/social situations that would limit 
compliance with study requirements.   
8. Moderate to significant immunosuppression (eg, active cancer, significant autoimmune 
disease) and/or receiving immunosuppressive drugs that result in moderate to significant 
immunosuppression (eg, low dose oral glucocorticoids do not necessarily exclude a 
patient)  
9. Known or previous hypersensitivity to HDACi 
10. History of congestive heart failure; cardiac arrhythmias; or other findings of ventricular 
dysfunction. 
11. Pregnancy or breast-feeding. 
3.3 
Informed Consent Process 
All participants must be provided a consent form describing the study with sufficient information 
for participants to make an informed decision regarding their participation.  Participants must 
sign the IRB-approved informed consent prior to participation in any study-specific procedure.  
The participant must receive a copy of the signed and dated consent document.  The original 
signed copy of the consent document must be retained in the subject’s research file.   
3.4 
Randomization Procedures 
This study does not have randomization.  All subjects must at least have one cutaneous BCC 
lesion and will apply topical remetinostat to BCCs.  If the subject has more than one BCC, a 
body map will remind subjects where to apply gel. 


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3.5 
Study Timeline 
Primary Completion: 
The study will reach primary completion 18 months from the time the study opens to accrual.  
Individual subjects will reach primary completion 6 weeks after starting topical remetinostat 
treatment.  
Study Completion: 
The study will reach study completion 24 months from the time the study opens to accrual, 
ie, allowing 6 months from Primary Completion for data analysis.  Individual subjects will 
complete the study about 13 weeks after starting topical remetinostat treatment (ie, Screening; 
6 weeks treatment; 4 to 6 weeks follow-up).   
4. 
TREATMENT PLAN 
Adult subjects in the clinic who have one or more cutaneous BCCs lesions greater than or equal 
to 5 mm in diameter, at least one of which is being biopsied as a normal course of care, will be 
invited to participate in this trial.  Eligibility of prospective participants will be confirmed, and 
subjects will enroll according to stated inclusion and exclusion criteria. 
Screening visits may be combined with or without Day 1 visit.   
Prospective participants must be willing to sign a consent form.  Subjects will also give consent 
to donate their BCC tissue for biomarker measurement and apply medication 3-times daily 
under bandage occlusion for 6 weeks.  The anticipated bandage will be an adhesive bandage 
(eg, “Band-Aid”) with a non-adherent dressing, or paper tape with a non-adherent dressing. 
Drug treatment:  Subjects will be instructed to apply topical remetinostat to individual BCCs 
3 times daily for 6 weeks.  Patients will discontinue application of the medication at 6 weeks, 
approximately 2 weeks prior to their surgical excision(s) scheduled for approximately Week 8. 
At least 1 target BCC will be identified requiring surgical excision per standard of care.  This 
lesion(s) will be measured and photographed and may be biopsied.  Week 8 biopsy may be 
collected at surgical excision of lesion(s).  Histopathological evaluation of the specimen may be 
performed to evaluate for tumor clearance. 
After an initial treatment application demonstration by the study team, treatment applications will 
be self-administered by the subject or a caregiver.  If requested, patient will receive a body map 
which will demonstrate where the lesion is on their body.  This will help the patient know where 
to apply the treatment drug.  Patients will receive oral and written administration instructions at 
the outset of the trial as follows: 
Study medication is to be applied to dry skin.  Apply the study medication to the BCC lesion(s) 
designated by your physician, 3 times daily for 6 weeks, using clean, washed finger(s)/hand as 
applicable.  Cover the treated BCC lesions(s) with a sticky strip bandage, such as a Band-Aid.  
If you start to treat new lesions or stop treating any lesion, please inform your physician so a 
record can be kept of which lesions are being treated with study medication.  There is no need 
to leave large amounts of residue on your skin.  If someone else helps apply the study 
medication, they should follow the same instructions.  Immediately following application, wipe 
the finger(s) and hands you have used to apply the study drug with a disposable tissue and 
wash your hands using soap and water.  If the study medication gets on the skin of other people 


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they should wash with soap and water.  Alternatively, you or a caregiver can wear disposable 
gloves to apply the study medication, which will be supplied to each patient on request. 
Diary: after an initial explanation by the study team at the first visit, patients will be asked to fill 
out a medication diary to document application of the study drug (see Appendix C).  Patients will 
be asked to fill this out daily and to bring their diary with them to each study visit for review by 
the study team. 
Medication Cooler: patients will be offered a small portable cooler to utilize to keep their study 
drug cold.  
Tumors to be treated will be clearly identified.  Patients will be instructed to store research 
medication in a refrigerator (see Appendix B). 
All tumors will be measured and photographed at baseline, 4 weeks and 6 weeks.   
Paper case report forms will be used to capture source data for this study.  A physician note will 
also be entered into Stanford’s electronic medical record system for each of the study visits. 
Given the absence of any remetinostat treatment-related systemic AEs, together with the lack of 
effect on laboratory parameters or EKG, the minimal levels of remetinostat detected 
systemically reported in clinical studies to date, and the small BSA (< 0.5%) that will be treated 
with remetinostat gel, no lab assessments will be performed with the exception of a serum 
pregnancy test for women of child-bearing potential at baseline to assess eligibility for 
enrollment.  Eligibility criteria will be used as baseline. 
Patients may be contacted weekly to check on compliance and to follow up on AEs.  Additional 
clinic visit(s) may be scheduled to assess AEs. 
It is anticipated that the entire target tumor(s) will be surgically removed at or after the 8th week 
or treatment, is accordance with regular medical care.  Patients will apply their last dose of 
Remetinostat 30 mins before surgical excision.  If surgical excision is delayed, ie, does not 
occur at Week 8, the drug may be continued for up to four weeks until surgical excision.  
Between Week 12 and Week 20, up to three attempts will be made to reach the patient for 
follow up phone call; the patient may also be seen for an in-person visit at the discretion of the 
investigator.  This visit may be in conjunction with surgery, a surgical follow-up visit, or the visit 
may be conducted by phone.  Patients may be contacted after completion of the study for 
additional follow up if deemed necessary by the study physician. 
BCC tissues will be collected from those who consent at baseline and Week 6 to measure the 
biomarker gene for BCCs treated with topical remetinostat gel 1%.  BCC biopsy will be collected 
in RNA later to measure biomarkers for BCC using real-time PCR. 
4.1 
General Concomitant Medication and Supportive Care Guidelines 
Concomitant therapy includes any prescription medications or over-the-counter preparations 
used by a subject between 1 month preceding the screening evaluation and the end of study 
visit. 
Subjects who use oral contraceptives, hormone-replacement therapy, or other maintenance 
therapy will continue their use.  All concomitant medications will be reported to the investigator 
and recorded on the appropriate CRF. 


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4.2 
Criteria for Removal from Study 
The trial will be terminated in the event of an SAE (Serious Adverse Event) related to the 
intervention.  A Serious Adverse Event is any of the following:   
• 
Fatal (ie, the AE actually causes or leads to death).   
• 
Life threatening (ie, the AE, in the view of the investigator, places the subject at 
immediate risk of death.  It does not include an AE that, had it occurred in a more severe 
form, might have caused death.).   
• 
Requires or prolongs inpatient hospitalization.   
• 
Results in persistent or significant disability/incapacity (ie, the AE results in substantial 
disruption of the subject’s ability to conduct normal life functions).   
• 
Any occurrence considered by the investigator to be a significant medical event (eg, may 
jeopardize the subject or may require medical/surgical intervention to prevent one of the 
medical outcomes listed above).  All AEs that do not meet any of the criteria for serious 
should be regarded as non-serious AEs.   
The investigator will use the following definitions to assess the relationship of the adverse event 
to the use of the study drug:   
• 
Probably-related:  An adverse event has a strong temporal relationship to the study 
drug or recurs on re-challenge and another etiology is unlikely or significantly less likely.   
• 
Possibly-related:  An adverse event has a strong temporal relationship to the study 
drug and an alternative etiology is equally or less likely compared the potential 
relationship to study drug.   
• 
Probably Not Related:  An adverse event has little or no temporal relationship to the 
study drug and/or a more likely alternative etiology exists. 
• 
Not Related:  An adverse even is due to an underlying or concurrent illness or effect of 
another drug and is not related to the study drug. 
Subjects may be removed from the study because of subject wishes, non-compliance, or 
development of any medical condition that puts the subject at increased risk, in the opinion of 
the investigator.   
The investigator has the right to discontinue a patient from study drug or withdraw a patient from 
the study at any time.  In addition, patients have the right to voluntarily discontinue study drug or 
withdraw from the study at any time for any reason.  Reasons for discontinuation of study drug 
or withdrawal from the study may include, but are not limited to, the following:  
• 
Any subject who presents at screening or during treatment with a large (> 25 mm) BCC 
lesion will be discontinued from treatment (if applicable) and referred for evaluation for 
surgical resection.  
• 
Subject withdrawal of consent at any time  
• 
Any medical condition that the investigator or Sponsor determines may jeopardize the 
patient’s safety if he or she continues in the study  
• 
Investigator determines it is in the best interest of the patient   


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• 
Surgical or other treatment of target BCC before Week 8 
• 
Pregnancy  
4.3 
Alternatives 
Alternatives to participation in the study include participating in a different clinical study, 
receiving medical care outside of a research study (including immediate surgical treatment), or 
no treatment. 
5. 
INVESTIGATIONAL AGENT INFORMATION 
5.1 
Investigational Agent  
Remetinostat, also known as suberohydroxamic acid phenyl ester (SHAPE);  SHAPE Gel;  
SHP-141; and 4-[[8-(hydroxyamino)-1,8-dioxooctyl]oxy]-benzoic acid methyl ester, Is a histone 
deacetylase inhibitor (HDACi) that was designed with a metabolically labile ester bond so that 
topical application would produce effective local histone deacetylase (HDAC) inhibition in 
cutaneous lesions while resulting in only negligible systemic HDAC inhibition.  
In this single-arm study, remetinostat is formulated at a strength of 1.0% in a gel consisting of 
dehydrated alcohol; propylene glycol;  hexylene glycol;  glycerin;  oleyl alcohol;  
diisopropyl adipate;  hydroxypropylcellulose;  butylated hydroxytoluene and citric acid 
(anhydrous).  The overall concentration of ethanol in the gel is approximately 50% (w/w).  
See the remetinostat Investigator Brochure for additional information including the mechanism 
of action; summaries of animal and clinical studies; non-clinical and clinical pharmacokinetic;  
major route of elimination;  safety profile;  and the non-clinical and clinical data supporting the 
dose and regimen chosen for this study. 
5.2 
Availability 
Medivir AB is providing drug for this study. 
5.3 
Agent Ordering 
Remetinostat will be ordered by the Principal Investigator and shipped directly to the Stanford 
Dermatology Clinic, where it will be stored per manufacturer’s guidelines and Stanford SOPs.  
Investigational drug will not be shipped to or held by Stanford Investigational Drug Services.  
The contact for drug ordering is: 
Medivir AB  
Box 1086 
Xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxx 
 
5.4 
Storage Conditions 
The Investigator is responsible for the control of drugs under investigation.  The study agent will 
be kept in a locked refrigerator (2 to 8ºC) in a secure area.  Only trained research staff will have 
access to the locked refrigerator.   


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5.5 
Agent Accountability 
Adequate records for the receipts (eg, Drug Receipt Record) and disposition (eg, Drug 
Dispensing Log) of the study drug will be maintained.  Accountability and subject compliance 
will be assessed by maintaining adequate “drug dispensing” and return records. 
Accurate records must be kept for each study drug provided by the Sponsor.  These records 
must contain the following information:   
• 
Documentation of drug shipments received from the Sponsor (date received, quantity, 
and tube number)  
• 
Disposition of unused study drug not dispensed to subject  
A Drug Dispensing Log will be kept current and will contain the following information:   
• 
The identification of the subject to whom the study medication was dispensed  
• 
The date(s), quantity, and kit number of the study medication dispensed to the subject.   
• 
The date(s), quantity and kit number of the study medication returned by the subject  
Subjects will be asked to return all used and unused drug supply containers during and at the 
end of the treatment, as a measure of compliance.  
The investigational product will be returned to the Sponsor for disposal, or with the agreement of 
the drug manufacturer, destroyed in accordance with institutional SOPs. 
6. 
DOSE MODIFICATIONS 
Detectable systemic levels of remetinostat after topical application for 6 weeks are not 
anticipated.  Treatment with topical remetinostat may be interrupted or dose modified as 
detailed below.  Subjects who require discontinuation of treatment for any reason will go 
off-study.  The Principal Investigator / Protocol Director will assess and determine if an 
individual subject needs to be off the study due to side effects.   
6.1. 
Dose Modifications due to Toxicity and Stopping Criteria 
Patients experiencing any treatment-related Grade 3 or higher local dermal irritation will be 
required to have their treatment exposure suspended until the irritation reduces to at least 
Grade 2.  Guidelines for dose reduction, interruption and discontinuation are provided below: 


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Table 1: Dose Modification 
Grade of 
Local Dermal 
Irritation 
Defining Clinical 
Signs 
Proposed Treatment Modification 
0 (No 
Reaction) 
None 
No action required; observation 
1 (Mild) 
Definite pink to red 
coloration 
2 (Moderate) 
Increased redness, with 
or without edema 
3 (Moderately 
Severe) 
Very red, with edema 
and vesiculation 
Treatment must be suspended until irritation 
improves to Grade 2 or lower (this must occur 
within 2 weeks).  After the irritation improves to 
Grade 2 or lower, treatment may be re-started, 
initially TID every second day, then increased to 
TID daily, if tolerated.  If dermal irritation does not 
improve to Grade 2 or lower after 2 weeks, 
treatment should be discontinued, and the 
patient withdrawn.  If event re-occurs, consider 
discontinuation of treatment. 
4 (Severe) 
Deep red, swelling and 
edema with bullae 
formation and necrosis 
Treatment must be suspended until irritation 
improves to Grade 2 or lower (this must occur 
within 2 weeks).  After the irritation improves to 
Grade 2 or lower, treatment may be re-started, 
initially TID every second day, then increased to 
TID daily, if tolerated.  If dermal irritation does not 
improve to Grade 2 or lower after 2 weeks, 
treatment should be discontinued, and the 
patient withdrawn.  If event re-occurs, consider 
discontinuation of treatment. 
Treatment will be stopped approximately 2 weeks before surgical excision if the PI determines 
that local dermal irritation may interfere with lesion identification at excision. 
Based on remetinostat safety data collected to date in earlier MF-CTCL studies, systemic 
adverse events are not anticipated. 
7. 
ADVERSE EVENTS AND REPORTING PROCEDURES 
7.1 
Potential Adverse Events 
Slight irritation of the skin was observed in some animal studies and was likely related to the 
ethanol in the formulation.   
Escalating doses of remetinostat gel were administered to different cohorts of patients to assess 
safety and tolerability in a Phase 1 study in patients with CTCL.  A total of 18 patients with 
CTCL were sequentially enrolled into one of three study cohorts consisting of six patients each.  
Within each study cohort of six patients, 5 were randomly assigned to receive remetinostat gel 
and 1 was randomly assigned to receive placebo.  Patients received treatment for a maximum 
of 28 days.  Three dose levels of remetinostat gel were evaluated at 0.1%, 0.5% and 1%.   


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The study drug was well-tolerated.  Eight patients, including one who received placebo, 
experienced 11 treatment-related adverse events.  The adverse events consisted of a skin 
burning or warming sensation, paraesthesia, and contact dermatitis and were all related to 
topical application of study drug to the index lesion treatment sites.  Ten of the treatment-related 
adverse events were mild (Grade 1) and one event (contact dermatitis) was Grade 2.  Only the 
Grade 2 event of contact dermatitis required treatment, for which topical steroid and moisturizer 
were applied after the patient completed the 28-day course of remetinostat gel treatment, which 
resolved.  All treatment-related adverse events had resolved prior to the Day 42 End-of-Study 
visit. 
There were no hematological findings among the 18 treated patients.  Among the 5 clinical 
laboratory changes reported as adverse events and the 4 clinical laboratory values that reached 
≥ Grade 2, none was related to study drug administration. 
For the phase 2 study, 60 patients were randomised in a 1:1:1 ratio to three treatment regimens 
of remetinostat gel (1% QD, 0.5% BID and 1% BID). Patients received treatment for 6 months 
and could continue on treatment for a further six months (12 months in total) if they received 
clinical benefit during the first 6-month period. 
Remetinostat gel at dosing regimens of 1% QD, 0.5% BID and 1% BID was generally 
well-tolerated, with no reports of adverse events associated with systemic HDAC inhibitors.  
There were 2 SAEs (acute heart failure and fracture), observed during the study considered 
unrelated to treatment with remetinostat. 
The most common adverse events were pruritus and skin irritation.   
Approximately half of the patients in each group reported AEs considered related to treatment; 
4 of these met CTCAE grade ≥ 3 for severity and all were skin-related: The rate of 
discontinuations due to treatment-related AEs was low, with no indication of a higher rate in the 
highest (1% BID) dose group.  Overall, the patients who had dose reduction/interruptions due to 
remetinostat related skin AEs in the 1% BID dose group stayed on treatment for a long time. 
The CTC grade 3 events resolved, patients wanted to stay on treatment despite these AEs 
(except for a single patient) and most of the patients (4 of 6) in this highest dose group who 
remained on drug for > 6 months received benefit, in terms of objective CAILS and/or pruritus 
responses. 
In the current study, skin will be carefully evaluated during treatment.  
Patients who develop contact dermatitis caused by the strip bandage adhesive per PI 
determination may discontinue bandage use. 
No systemic abnormalities were found at any dose level in the nonclinical studies and no 
treatment-related observations other than those above were noted in any clinical trial.  Thus, no 
special precautions are anticipated. 
The effect of remetinostat in pregnancy has not been studied.  Similarly, excretion of 
remetinostat into breast milk has not been examined.  Therefore, pregnant and lactating women 
are excluded from clinical trials at this time. 
Remetinostat is considered unlikely to be a photo-irritant as SHP-141 absorbs light at a 
maximum of 234 nm in the UV/visible spectrum and does not meaningfully absorb light above 
290 nm.  Photo-irritation has not been observed in clinical trials of remetinostat gel. 
There is no information to indicate that abuse or dependency would occur with exposure to 
remetinostat gel.  
Detectable systemic levels of remetinostat after topical application are not anticipated.   


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See the Investigator Brochure for details on AEs captured to date from CTCL study. 
7.2 
Adverse Event Reporting 
For guidance on reporting adverse events, refer to the Stanford Cancer Institute Clinical 
Trials Office Adverse Event SOP.  
Adverse events will be graded according to CTCAE v5.0.  Both Serious and Non-Serious 
Adverse Events will be clearly noted in source documentation and listed on study specific Case 
Report Forms (CRFs).  The Protocol Director (PD) or designee will assess each Adverse 
Event (AE) to determine whether it is unexpected according to the Investigator’s Brochure 
and/or protocol and related to the a) study drug and b) the investigation.  All Serious Adverse 
Events (SAEs) will be tracked until resolution or until 30 days after the last dose of the study 
treatment.  
All AE and SAEs will be reported to the Principal Investigator.  The Stanford Cancer Institute 
Data and Safety Monitoring Committee (DSMC) will be informed of all SAEs.  An AE is any 
unfavorable and unintended sign, symptom, or disease temporally associated with the use of an 
investigational medicinal product (IMP) or other protocol-imposed intervention, in this study 
topical remetinostat, regardless of attribution.  This includes the following:  AEs not previously 
observed in the subject that emerge during the protocol specified AE reporting period, including 
signs or symptoms associated with basal cell nevus syndrome that were not present prior to the 
AE reporting period; complications that occur as a result of protocol-mandated interventions 
(eg, invasive procedures such as biopsies); and preexisting medical conditions judged by the 
investigator to have worsened in severity or frequency or changed in character during the 
protocol-specified AE reporting period. 
SAEs CTCAE Grade 3 and above, and all subsequent follow-up reports will be reported to the 
Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) using the 
study-specific CRF regardless of the event’s relatedness to the investigation.  Following review 
by the DSMC, events meeting the IRB definition of ‘Unanticipated Problem’ will be reported to 
the IRB using eProtocol within 10 working days of DSMC review, or within 5 working days for 
deaths or life-threatening experiences. 
Female patients of childbearing potential will be instructed to immediately inform the investigator 
if they become pregnant during the study or within 3 months after the last application of study 
drug. 
The investigator will discontinue study drug and counsel the patient, discussing the risks of the 
pregnancy and the possible effects on the fetus.  Monitoring of the patient should continue until 
conclusion of the pregnancy.  Any SAEs associated with the pregnancy (eg, an event in the 
fetus;  an event in the mother during or after the pregnancy;  or a congenital anomaly/birth 
defect in the child) will be reported per Stanford SOPs.  
Male patients will be instructed to immediately inform the investigator if their partner becomes 
pregnant during the study or within 3 months after the last application of study drug.  
In addition to the above reporting procedures, all Serious Adverse Events (SAEs) and 
occurrences of pregnancy reports which occur in remetinostat investigator-initiated studies will 
be reported to Medivir AB.  The responsibility of receipt and processing of the above-mentioned 
cases has been outsourced to a consultancy company, Diamond PV Services Ltd. 


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SAEs 
Upon becoming aware of an SAE, the SAE form in Appendix D will be completed and sent to 
Diamond PV Services via fax or email.  Events will be reported within 24 hours of becoming 
aware of the event. 
All SAEs that occur from the time of signing informed consent until 30 days following cessation 
of treatment will be reported.  In addition, any SAEs that occur after this period and are 
considered to be related to the study drug or the study procedure will be reported. 
Pregnancies or lactation cases 
All pregnancies or lactation cases that occur in the subject or partner of the subject’s (regarding 
pregnancy cases only) enrolled in the study will be reported on the pregnancy report form 
(Appendix C) from the time of signing informed consent to within 3 months after the last 
application of the study drug. 
Acknowledgement and queries 
Diamond PV shall confirm receipt of the report within 1 business day.  If an acknowledgement of 
receipt is not received within 1 business day, the report will be resent. 
If Diamond PV has any follow up queries regarding the report they will send queries to the site 
via e-mail.  The query letter will state the due date for receipt of the queries.  All query letters will 
be responded to within the specified timelines.  If the information requested is not available, the 
query letter responses will state this.  All data provided will be in line with local data privacy 
regulations. 
Updates to case reports 
If additional information or changes to the information become available, an updated report form 
indicating the additional or amended information will be provided.  If there is new information in 
the follow-up case report, this will be highlighted with an asterisk on the paper report form, with 
the reporter’s initials and date of new information added.  The updated form will be sent via fax 
or email. 
Receipt of Suspected Unexpected Serious Adverse Reaction reports: 
All reports of Suspected Unexpected Serious Adverse Reactions will be sent to sites by 
Diamond PV.  Upon receipt of such a report, it will be reviewed, and a copy submitted to the 
IRB, and a copy filed in the Investigator file. 
All SUSAR report letters shall have an acknowledgment of receipt attached which will be 
completed and returned to Diamond PV via fax to confirm that it has been received, reviewed 
and submitted as appropriate. 
Pharmacovigilance contact person: 
Tel: +xxxxxxxx 
Local US no.; xxxxxxxxxxx 
Fax:  
Local US no xxxxxxxxxxxx 
Email:  xxxxxxxxxxxxxxxx 


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8. EXPLORATIVE / CORRELATIVE / SPECIAL STUDIES  
For the Exploratory Studies, PD endpoints will include, but are not limited to, 
• 
To assess local pharmacodynamics (PD) effects of remetinostat by 
immunohistochemistry on BCC biopsy sections, including histone acetylation. 
8.1. 
Increased Acetylation of HDAC Substrates as a PD Marker 
The Exploratory Objectives aim to determine by IHC on FFPE BCC tissues with indicated 
antibodies if topical remetinostat modulate the levels of acetylated-histone H3. Prior phase 2 
clinical trial data have shown a clear reduction the levels of acetylated line in skin from 
CTCL-patients subjected to treatment with remetinostat.  
8.2. 
Measurement Definition 
This study will measure the levels of acetylation in BCC FFPE histology sections in situ.  
8.3. 
Analysis Population 
The analysis population for this objective is planned to include at least 5 subjects who have 
consented to undergo remetinostat treatment, and who also consent to have at baseline and 
post-treatment BCC biopsies (“paired BCC tumor samples”).  In addition, subjects who had their 
tumor extracted at the end of the study without prior baseline biopsy can be included and 
assessed in comparison to untreated archival FFPE BCC tissues (“unpaired BCC tumor 
samples”). 
8.4. 
Measurement Methods 
Levels of histone acetylation in BCC will be measured by immunohistochemistry (IHC).  
Biopsies of BCC tumors will be processed as for standard histology and stored in FFPE-blocks.  
Biopsy FFPE blocks will be cut into 5-µm sections and oriented longitudinally on the slides to 
ensure sufficient representation of skin histology and lesion depth.  Appropriate designated 
archival BCC FFPE-blocks based on tumor size and treatment history may be identified and 
retrieved from Stanford.  FFPE-blocks or cut sections will be shipped to Medivir (funding 
sponsor) or to a by Medivir-designated CRO for IHC staining and analysis (see section 8.5 
Analysis Plan).  
8.5. 
Analysis Plan 
Staining intensities of acetylated histones will be analyzed in paired BCC tumor samples relative 
to baseline and in unpaired BCC tumor samples relative to archival BCC tumors.  
 


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9. STUDY CALENDAR 
 Eligibility testing not shown 
Screening 
Day -2 to -30 
Screening Day -1 
Treatment 
Day 1 
Treatment 
Week 4* 
(+/- 1 week) 
Week 6 
Visit** 
(+/- 2 week) 
Follow-up 
Week 12* 
(+/- 1 week) 
Early termination 
Remetinostat treatment 
 
 
X 
X 
X 
 
 
Informed consent 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Concurrent meds 
X------------------------------------------------------------------------------------------------------► 
Physical exam 
X 
X 
 
X 
X 
X 
X 
Vital signs 
X 
X 
 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
Weight 
X 
X 
 
X 
X 
 
X 
ECOG score 
X 
 
 
X 
X 
 
X 
Serum pregnancy test  
X 
 
 
 
 
 
 
Adverse event evaluation 
 
 
X---------------------------------------------------------------------► 
Tumor measurements and 
photographs 
 
X 
 
X 
X 
 
X 
Tumor Biopsy  
 
X 
 
 
(X) 
 
Patient Calls 
 
 
X-----------------------------------------------► 
 
*    Week 4 visit and Follow up visit may occur +/- 1week to accommodate patient and physician schedules 
**   Week 6 visits may occur +/- 2 weeks to accommodate patient and physician/surgeon schedules 
Screening visits may be combined with or without day 1 visit


 
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10. MEASUREMENTS 
For clinicaltrials.gov and Stanford Clinical Trials Directory compliance  
10.1  Primary Outcome  
Primary outcome measure:  BCC response 
The primary outcome of this study is to determine if topical remetinostat will reduce BCC tumors 
size.  A partial response is defined as at least 30% decrease in total tumor diameter at end of 
study from baseline.  A complete response is undetectable tumor lesions at end of study.  
Objective response rate (ORR) will defined as the proportion of subjects with either a complete 
response or a partial response (PR) among all eligible and treated subjects.  Toxicities will be 
graded according to the National Cancer Institute CTCAE v5.0.  Exact binomial 90% confidence 
intervals (Cis) will be computed for the ORR.   
10.1.1 No subset analysis 
10.1.2 Measurement Definition 
The diameter of BCC tumors treated with topical remetinostat gel will be measured with calipers 
throughout the study to determine if topical remetinostat could reduce BCC tumors size 
comparing to baseline.   
10.1.3 Measurement Methods 
BCC tumors will be photographed measured using a ruler and calipers and the tumors size 
(longest diameter) will be recorded in millimeters.   
10.1.4 Measurement Time Points 
BCCs will be measured at baseline, 4 weeks and 6 weeks.  
10.1.5 Response Review 
Overall response rate of BCC in subjects as defined by at least 30% decrease in tumor size at 
end of study as compared to baseline.  All responses will be reviewed by an expert(s) 
independent of the study at the study’s completion.  Simultaneous review of the subjects’ files 
and tumor photographs will be performed.   
10.1.6 Measurement Time Points 
BCC biopsies may be performed at baseline and end of trial.  We are expecting to process all 
samples in six months after the last subject tumors collection is completed.   
11. 
REGULATORY CONSIDERATIONS 
11.1 
Institutional Review of Protocol 
The protocol, the proposed informed consent and all forms of participant information related to 
the study (eg, advertisements used to recruit participants) will be reviewed and approved by the 
Stanford IRB and Stanford Cancer Institute Scientific Review Committee (SRC).  Any changes 
made to the protocol will be submitted as a modification and will be approved by the IRB prior to 


 
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implementation.  The Protocol Director will disseminate the protocol amendment information to 
all participating investigators. 
11.2 
Data and Safety Monitoring Plan 
The Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) will be the 
monitoring entity for this study.  The DSMC will audit study-related activities to determine 
whether the study has been conducted in accordance with the protocol, local standard operating 
procedures, FDA regulations, and Good Clinical Practice (GCP).  This may include review of the 
following types of documents participating in the study: regulatory binders, case report forms, 
eligibility checklists, and source documents.  In addition, the DSMC will regularly review serious 
adverse events and protocol deviations associated with the research to ensure the protection of 
human subjects.  Results of the DSMC audit will be communicated to the IRB and the 
appropriate regulatory authorities at the time of continuing review, or in an expedited fashion, as 
needed. 
11.3 
Data Management Plan 
The Protocol Director, or a designee, will prepare and maintain adequate and accurate 
participant case histories with observations and data pertinent to the study.  Study-specific case 
report forms (CRFs) will be developed to document treatment outcomes for data analysis.  
These CRFs will initially be developed on paper forms by the study coordinator, but may 
transition to electronic forms (ie, in OnCore or RedCap).  Subject charts will be kept in a locked 
office, only accessible to the research team. 
12. 
STATISTICAL CONSIDERATIONS 
12.1 
Statistical Design 
The Primary Objective and Primary Outcome of this study is to determine if topical remetinostat 
will reduce BCC tumors size, as defined by at least 30% decrease in BCC tumor diameter at 
end of study as compared with baseline.  Complete response (CR) will be defined as no 
clinically detectable tumor at EOS.  ORR is defined as the proportion of tumors with either a 
complete response or a partial response (PR) among all eligible and treated lesions.  Exact 
binomial 90% confidence intervals (Cis) will be computed for the ORR.  With a planned analysis 
on 30 BCCs, this study should provide 91% power to reject an ORR of 15% if the true ORR is 
40% or better, at one sided-alpha level of 0.05 with at least 9 responders.  
12.2 
Randomization 
Not applicable, as this is a single-arm trial. 
12.3 
Interim analyses 
None planned 
12.4 
Descriptive Statistics and Exploratory Data Analysis 
The baseline characteristics of study subjects (age, gender, skin type, number of tumors, 
average size of tumors, tumor location, tumor histology, and prior treatments) will be 
summarized in tables.  Wilcoxon signed rank tests for continuous variables and chi-square tests 
for dichotomous variables will be used.  CONSORT guidelines will be followed to describe the 


 
IRB-40947  
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 2 October 2020  
number of subjects screened, enrolled, and completed the treatment.  All AEs will be described 
in tabular format.  
12.5 
Primary Analysis  
The primary endpoint is the overall response rate of BCC lesions as defined by at least 30% 
decrease in tumor size at EOS as compared to baseline. 
12.5.1 Analysis Population 
We will first analyze the data by intention to treat analysis and then per-protocol analysis by only 
including subjects that are > 70% compliant with drug treatment (patients who are 69% or less 
compliant will be reported as a deviation; patients who are 70% compliant will not be recorded 
as a deviation).  For subjects who drop out, we will use data from their last study visit if they 
contribute a biopsy.  The analysis population will include participants who have consented to 
undergo remetinostat treatment and who have at least 1 BCC tumor.   
Safety analyses will include all subjects who received at least one dose of study treatment.  
Graded AEs (number and percent) will be summarized and reported according to the NCI 
CTCAE v5.0. 
12.5.2 Analysis Plan 
We will analyze the overall response rate of BCC based on change of longest diameter of 
tumor.  Objective response rate (ORR) will defined as the proportion of subjects with either a 
complete response or a partial response (PR) among all eligible and treated subjects.  Toxicities 
will be graded according to the National Cancer Institute CTCAE v5.0.  Exact binomial 90% 
confidence intervals (CIs) will be computed for the ORR.  With a planned analysis on 30 BCCs, 
this study would provide 91% power to reject an ORR of 15% if the true ORR is 40% or better, 
at one-sided alpha level of 0.05 with at least 9 responders. 
12.6 
Secondary Analysis  
12.6.1 Secondary Objective Measure:  Reduction in GLI1 expression 
Secondary Objective 1 is to determine whether topical remetinostat reduces the BCC biomarker 
GLI1 as compared to baseline.  Based on prior clinical trials, it is estimated that topical 
remetinostat would need to decrease the Hh pathway by at least 50% to have a 
clinically-significant anti-BCC effect in subjects.  This will provide insight into whether 
remetinostat is an effective chemotherapeutic for BCC.  
12.6.1.1 
Measurement Definition 
This study will measure GLI1 mRNA, representing Hedgehog target gene (GLI1) expression, in 
samples of BCC tumors using real-time QPCR.  
12.6.1.2 
Analysis Population 
The analysis population for this objective is planned to include at least 10 subjects who have 
consented to undergo remetinostat treatment, and who also consent to have at baseline and 
post-treatment BCC biopsies (“paired BCC tumor samples”).  


 
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12.6.1.3 
Measurement Methods 
HH target gene (GLI1) expression in BCCs will be measured using real-time PCR.  Biopsies of 
BCC tumors will be placed in RNAlater and stored at -80°C prior to analysis.  Total RNA will be 
isolated from the collected BCCs using a RNeasy Fibrous Tissue Mini Kit 
(Qiagen, Valencia, CA) according to the manufacture’s protocol.  The RNA obtained will then be 
quantified using A260/A280 spectrophotometry.  DNase treated RNA (2 µg) will reverse 
transcribed using the High Capacity RNA-to-cDNA kit (Like Technologies, Grand Island, 
New York).  The obtained cDNA will be used in 20 µL PCR reactions containing 10 µL Maxima 
SYBR Green qPCR Master Mixes (Thermo Scientific, Pittsburg, Pennsylvania) 0.4 µL primers, 
0.86 µL of cDNA template sample, and 8.74 µL of molecular grade water.  Reactions will be 
performed in 284-well PCR plates and read on an ABI Prism 7900HT Sequence Detection 
System.   
12.6.1.4 
Analysis Plan 
Post-treatment GLI1 mRNA levels in the paired BCC sample sets will be compared with 
baseline GLI1 levels for the respective subject to calculate percent change in GLI1 mRNA 
expression.  Because GLI levels are not expected to be normally distributed, the comparison will 
be conducted using the using Wilcoxon signed rank test.  
Data will be analyzed using the comparative CT method as a means of relative quantitation, 
normalized to an endogenous reference (HPRT cDNA) and relative to a calibrator (normalized 
Ct value obtained from controls) and expressed as the 2-∆∆Ct algorithm (also known as the 
delta-delta-Ct or ddCt algorithm) according to Applied Biosystems User Bulletin 2:  Rev B, 
“Relative Quantitation of Gene Expression.” 
With a sample size of at least 10 paired-BCCs, the study will have greater than 98% power to 
detect a 43% (SD:  30%) decrease in GLI1 mRNA levels at 2-sided alpha level 0.05 assuming 
no change in GLI mRNA levels without remetinostat (effect size = 1.0, Wilcoxon signed 
rank test).  This should provide sufficient power to determine whether topical remetinostat can 
block the hedgehog pathway in humans to the degree required to be an effective 
chemotherapeutic.  
12.6.2 Secondary Objective Measure:  Safety 
For Secondary Objective 1, toxicities will be graded according to the National Cancer Institute 
CTCAE v5.0.  The safety of remetinostat when applied topically for 6 weeks will be assess as 
follows: 
• 
Incidence, type, and severity of adverse events (AEs)  
• 
Incidence and nature of serious adverse events (SAEs)  
• 
Incidence of AEs leading to remetinostat discontinuation or interruption  
• 
Adherence to the treatment, measured by number of patients discontinuing the treatment 
(for any reason) and treatment interruptions  


 
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12.7  Sample Size 
12.7.1 Overall Accrual estimates 
Subjects will be enrolled from Stanford Dermatology (Adult) clinic which sees approximately 
4,000 dermatology patients per month (or 48,000 visits per year).  Approximately 20% of these 
patients have current or past skin cancer.  Enrollment of BCC subjects for Stanford clinical trials 
has been rapid.  We anticipate to be able to enroll 30 per-protocol BCC lesions within the first 
12 months.  We will only advertise and enroll from Stanford Dermatology clinic.  It is anticipated 
that at least 10 subjects will consent to baseline and post-treatment biopsies.   
12.7.2 Sample size justification 
For primary objective analysis, with a planned analysis on 30 BCCs, this study would provide 
91% power to reject an ORR of 15% if the true ORR is 40% or better, at one-sided alpha level 
of 0.05 with at least 9 responders. 
For secondary outcome analysis, with a sample size of 10 paired BCC tumors, we will be able 
to detect a 43% decrease in GLI mRNA levels (SD:  30%) with 98% power at a two-sided alpha 
level of 0.05 assuming no change in GLI levels without remetinostat (effect size = 1.0, Wilcoxon 
signed rank test) 
12.7.3 Effect size justification 
This is a single-arm (non-randomized) study of topical remetinostat.  BCCs are not anticipated 
to self-regress in the absence of any treatment. 
12.8 
Criteria for future studies 
If topical remetinostat reduces BCC size, it is anticipated that a larger, randomized, controlled 
trial will be proposed. 


 
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13. 
REFERENCES 
Aszterbaum M, et al.  “Ultraviolet and ionizing radiation enhance the growth of BCCs and 
trichoblastomas in patched heterozygous mice.”  Nature Med.  1999;5:1285-1291.   
Athar M, et al.  “Inhibition of smoothened signaling prevents ultraviolet B-induced basal cell 
carcinomas through regulation of Fas expression and apoptosis.”  Cancer Res.  
2004;64:7545-7552. 
Binns W, et al.  “A congenital cyclopan-type malformation in lambs induced by maternal 
ingestion of a range plant, Veratrum Californicum.”  A J Vet Res.  1963;24:1164-1175.   
Bree AF, et al.  “Consensus statement from the first international colloquium on basal cell nevus 
syndrome (BCNS).”  Am J Med Genet A.  Sept 2011;155A(9):2091-2097.  
Canettieri G, Di Marcotullio L, Greco A, et al.  “Histone deacetylase and 
Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli 
acetylation.”  Nat Cell Biol.  2010;12(2):132-142. 
Chen JK, et al.  “Inhibition of hedgehog signaling by direct binding to Smoothened.  Genes Dev 
2002;16:2743-2748.  
Eisenhauer EA, et al.  “New response evaluation criteria in solid tumours:  revised RECIST 
guideline (version 1.1).”  Eur J Cancer.  2009;45:228-247. 
Epstein, E.H.  (2008).  “Basal cell carcinomas:  attack of the hedgehog.”  Nat Rev Cancer.   
8:743-754. 
Gorlin RJ.  “Nevoid basal cell carcinoma syndrome.  Medicine.  1997;66:98-109. 
Hahn H, Wicking C, et al.  “Mutations of the human hemolog of Drosophila patched in the 
nevoid basal cell carcinoma syndrome.”  Cell.  1996;85(6):841-51. 
Johnson RL, et al.  “Human homolog of patched, a candidate gene for the basal cell nevus 
syndrome.”  Science.  1996;272:1668-1671.   
Kim J, et al.  :Itraconazole, a commonly used antifungal inhibits hedgehog pathway activity and 
cancer growth.”  Cancer Cell.  2011;17:388-399. 
Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R.  “FDA approval summary:  vorinostat 
for treatment of advanced primary cutaneous T-cell lymphoma.”  Oncologist.  
2007;12(10):1247-1252. 
Miller DL, and Weinstock MA.  “Nonmelanoma skin cancer in the United States:  incidence.”  
J Am Acad Dermatol.  1994;30(5Pt1):774-778.   
Peck GL, et al.  “Treatment and prevention of basal cell carcinoma with oral isotretinoin.”  
J Am Acad Dermatol.  1988;19:176-185. 
Raffel C, Jenkins RB, Frederick L, et al.  “Sporadic medulloblastomas contain PTCH 
mutations.”  Cancer Res.  1997;57:842-845. 
Reifenberger J, et al.  “Missense mutations in SMOH in sporadic basal cell carcinomas of the 
skin and primitive neuroectodermal tumors of the central nervous system.”  Cancer Res.  
1998;58:1798-17803 
Tangrea JA, Edwards BK, et al.  “Long-term therapy with low-dose isotretinoin for prevention 
of basal cell carcinoma:  a multicenter clinical trial.  Isotretinoin-basal cell carcinoma study 
group.”  J Natl Cancer Inst.  1992;84(5):328-32.  
Xie J, Johnson RL, et al.  “Mutations of the PATCHED gene in several types of sporadic 
extracutaneus tumors.”  Cancer Res.  1997;57:2369-2372. 


 
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APPENDIX A:  Participant Eligibility Checklist  
Participant Eligibility Checklist must be completed in its entirety for each subject prior to registration.  The 
completed, signed, and dated checklist must be retained in the subject’s study file and the study’s 
Regulatory Binder.   
The study coordinator, treating physician and an independent reviewer must verify that the participant’s 
eligibility is accurate, complete, and legible in source records.  A description of the eligibility verification 
process should be included in the EPIC or other Electronic Medical Record progress note.   
Protocol Title: 
A Phase 2 Open-label, Single-arm Trial to Investigate the Efficacy and Safety 
of Topical Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing 
Surgical Resection of Basal Cell Carcinoma (BCC) 
Protocol Number: 
IRB-40947 
Principal Investigator: 
Kavita Sarin, MD, PhD 
II.  Subject Information: 
Subject Name / ID: 
 
Gender:    
 Male     
 Female 
III.  Study Information: 
SRC-approved 
    IRB-approved 
   Contract signed 
   
Inclusion Criteria 
(From IRB-approved protocol) 
Yes No N/A 
Supporting 
Documentation* 
1 
Must have at least one cutaneous BCC lesion greater than or 
equal to 5 mm. BCC lesion(s) can be superficial, nodular, 
micronodular, or morpheaform BCC, but must be amenable to 
surgical resection. 
 
 
 
 
2 
18 years of age or older 
 
 
 
 
3 
Must be willing to apply the topical remetinostat 3 times daily 
for 6 weeks and cover with an occlusive bandage. 
 
 
 
 
4 
Negative serum pregnancy test within 14 days prior to the first 
dose of study therapy for women of child-bearing potential, 
defined as a sexually mature woman who has not undergone a 
hysterectomy or who has not been naturally postmenopausal 
for at least 24 consecutive months (ie, who has had menses 
any time in the preceding 24 consecutive months) 
 
 
 
 
5 
Sexually active women of child bearing potential (WCBP) and 
male patients with a female partner of child-bearing potential 
must agree to use acceptable methods of contraception to 
avoid pregnancy (for example, oral, injectable, or implantable 
hormonal contraceptive; tubal ligation; intra-uterine device; 
barrier contraceptive with spermicide; or vasectomized 
partner) before the first dose of study therapy and for 3 months 
after the last dose of study therapy 
 
 
 
 
6 
Has signed and dated the current IRB-approved informed 
consent document 
 
 
 
 
 
Exclusion Criteria 
(From IRB-approved protocol) 
Yes No N/A 
Supporting 
Documentation* 
1 
Any large (> 25 mm) BCC lesion. Patients with large BCC 
lesion(s) will be referred for evaluation for surgical resection. 
 
 
 
 
2 
Inoperable locally-advanced and/or non-cutaneous metastatic 
 
 
 
 


 
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BCC 
3 
Taking any medication known to affect HH signaling pathway 
such as itraconazole 
 
 
 
 
4 
Within the past 6 months, has used topical or systemic 
therapies that might interfere with the evaluation of the study 
medication during the study. Specifically, these include the 
topical use to the study tumors of:  
o 
Glucocorticoids applied topically at the tumor site (low 
dose oral glucocorticoids do not necessarily exclude a 
patient) 
o 
Retinoids either systemically or topically at the tumor site 
(eg, etretinate, isotretinoin, tazarotene, tretinoin, 
adapalene)  
o 
Alpha-hydroxy acids (eg, glycolic acid, lactic acid) to 
> 5% of the skin or to the tumor site 
o 
5-fluorouracil or imiquimod and/or  
o 
Itraconazole 
 
 
 
 
5 
Has received treatment with systemic chemotherapy or 
agents known to be inhibitors of HH signaling, within 60 days 
prior to starting study medication 
 
 
 
 
6 
Currently receiving systemic medications that could affect 
BCC tumors (eg, oral retinoids) or might interact with 
remetinostat 
 
 
 
 
7 
Uncontrolled intercurrent illness including, but not limited to, 
ongoing or active infection, recurrent seizure history or 
psychiatric illness/social situations that would limit 
compliance with study requirements 
 
 
 
 
8 
Moderate to significant immunosuppression (eg, active 
cancer, significant autoimmune disease) and/or receiving 
immunosuppressive drugs that result in moderate to 
significant immunosuppression (e.g. low dose oral 
glucocorticoids do not necessarily exclude a patient) 
 
 
 
 
9 
Known or previous hypersensitivity to HDACi 
 
 
 
 
10 
History of congestive heart failure; cardiac arrhythmias; or 
other findings of ventricular dysfunction 
 
 
 
 
11 
Pregnancy or breast-feeding 
 
 
 
 
IV.  Statement of Eligibility 
By signing this form of this trial I verify that this subject is [
 eligible / 
 ineligible] for participation in 
the study.  This study is approved by the Stanford Cancer Institute Scientific Review Committee, the 
Stanford IRB, and has finalized financial and contractual agreements as required by Stanford School of 
Medicine’s Research Management Group.   
Investigator Signature: 
Date: 
Printed Name: 
Secondary Reviewer Signature: 
Date: 
Printed Name: 
Tertiary Reviewer Signature: 
Date: 
Printed Name: 


 
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APPENDIX B:  Study IRB-40947 Participant Information Sheet 
Remetinostat Information Sheet 
Remetinostat Application instructions:  
Remetinostat gel 1% is to be applied to dry skin.  Wash your hands and squeeze the amount of 
study medication that was demonstrated by the study team from the tube onto your index finger, 
and apply to the BCC lesion(s) identified by your physician.  Apply to the BCC lesion(s) 3 times 
daily for 6 weeks as specified by your physician. Cover the treated BCC lesions(s) with a sticky 
strip bandage, such as a Band-Aid.   
There is no need to leave large amounts of residue on your skin. Immediately following 
application, wipe the finger(s) and hands you have used to apply the study drug with a 
disposable tissue and wash your hands using soap and water. If the study medication gets on 
the skin of other people they should wash with soap and water. 
If someone else helps apply the study medication, they should follow the same instructions.  
If you start to treat new lesions or stop treating any lesion, please inform your physician so a 
record can be kept of which lesions are being treated with study medication. 
Remetinostat Storage Instructions:  
• 
Do not store the study medication in your car.  
• 
Study medication should be stored in the refrigerator, away from heat or open flame.  
• 
The study medication should be kept out of reach of children and unauthorized persons 
(not being patients participating in this study or their caregiver).  
Risks from Remetinostat: 
In prior studies, remetinostat caused some people to have some skin irritation such as a tingling 
or tickling feeling (“pins and needles”) on their skin, a warm or burning feeling on their skin or 
inflammation (redness and swelling).  
This may be due to the ingredients the drug is mixed in, or the drug itself. 
 
 


 
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APPENDIX C:  Study IRB-40947 Participant Medication Application Diary 
Study Participant Study Drug Application Diary 
 
 
 
 
Participant Identifier: BCC-_______ 
STUDY DRUG INSTRUCTIONS: 
Study Drug: Remetinostat 1% gel 
How Much:  Apply a thin layer over the tumor(s) identified by the 
study doctor. 
How Often: Three times daily. 
When: You should apply the gel in the morning, at mid-day, and in 
the evening. 
SPECIAL INSTRUCTIONS: 
This medication must remain refrigerated at all times. 
Cover the area with a bandage after you apply the gel. 
Wash your hands after you apply the gel. 
APPLICATION LOG 
Please indicate if you applied the gel for each dose listed below. 
Please bring this diary to your next clinic visit. 
 
  
Date 
Gel Applied 
  
Dose 1 
Dose 2 
Dose 3 
Comments 
Example 
1/1/18 
x 
x 
x 
Stinging after medication applied 
Day 1 
<prepopulated date> 
 
 
 
 
Day 2 
<prepopulated date> 
 
 
 
 
Day 3 
<prepopulated date> 
 
 
 
 
Day 4 
<prepopulated date> 
 
 
 
 
Day 5 
<prepopulated date> 
 
 
 
 
Day 6 
<prepopulated date> 
 
 
 
 
Day 7 
<prepopulated date> 
 
 
 
 
Day 8 
<prepopulated date> 
 
 
 
 
Day 9 
<prepopulated date> 
 
 
 
 
Day 10 
<prepopulated date> 
 
 
 
 
Day 11 
<prepopulated date> 
 
 
 
 
Day 12 
<prepopulated date> 
 
 
 
 
Day 13 
<prepopulated date> 
 
 
 
 
Day 14 
<prepopulated date> 
 
 
 
 


 
IRB-40947  
Page 35 of 51 
 2 October 2020  
  
Date 
Gel Applied 
  
Dose 1 
Dose 2 
Dose 3 
Comments 
Day 15 
<prepopulated date> 
 
 
 
 
Day 16 
<prepopulated date> 
 
 
 
 
Day 17 
<prepopulated date> 
 
 
 
 
Day 18 
<prepopulated date> 
 
 
 
 
Day 19 
<prepopulated date> 
 
 
 
 
Day 20 
<prepopulated date> 
 
 
 
 
Day 21 
<prepopulated date> 
 
 
 
 
Day 22 
<prepopulated date> 
 
 
 
 
Day 23 
<prepopulated date> 
 
 
 
 
Day 24 
<prepopulated date> 
 
 
 
 
Day 25 
<prepopulated date> 
 
 
 
 
Day 26 
<prepopulated date> 
 
 
 
 
Day 27 
<prepopulated date> 
 
 
 
 
Day 28 
<prepopulated date> 
 
 
 
 
Day 29 
<prepopulated date> 
 
 
 
 
Day 30 
<prepopulated date> 
 
 
 
 
Day 31 
<prepopulated date> 
 
 
 
 
Day 32 
<prepopulated date> 
 
 
 
 
Day 33 
<prepopulated date> 
 
 
 
 
Day 34 
<prepopulated date> 
 
 
 
 
Day 35 
<prepopulated date> 
 
 
 
 
Day 36 
<prepopulated date> 
 
 
 
 
Day 37 
<prepopulated date> 
 
 
 
 
Day 38 
<prepopulated date> 
 
 
 
 
Day 39 
<prepopulated date> 
 
 
 
 
Day 40 
<prepopulated date> 
 
 
 
 
Day 41 
<prepopulated date> 
 
 
 
 
Day 42 
<prepopulated date> 
 
 
 
 
Day 43 
<prepopulated date> 
 
 
 
 
Day 44 
<prepopulated date> 
 
 
 
 
Day 45 
<prepopulated date> 
 
 
 
 
Day 46 
<prepopulated date> 
 
 
 
 
Day 47 
<prepopulated date> 
 
 
 
 
Day 48 
<prepopulated date> 
 
 
 
 
Day 49 
<prepopulated date> 
 
 
 
 
Day 50 
<prepopulated date> 
 
 
 
 


 
IRB-40947  
Page 36 of 51 
 2 October 2020  
  
Date 
Gel Applied 
  
Dose 1 
Dose 2 
Dose 3 
Comments 
Day 51 
<prepopulated date> 
 
 
 
 
Day 52 
<prepopulated date> 
 
 
 
 
Day 53 
<prepopulated date> 
 
 
 
 
Day 54 
<prepopulated date> 
 
 
 
 
Day 55 
<prepopulated date> 
 
 
 
 
Day 56 
<prepopulated date> 
 
 
 
 
Day 57 
<prepopulated date> 
 
 
 
 
Day 58 
<prepopulated date> 
 
 
 
 
Day 59 
<prepopulated date> 
 
 
 
 
Day 60 
<prepopulated date> 
 
 
 
 
Day 61 
<prepopulated date> 
 
 
 
 
Day 62 
<prepopulated date> 
 
 
 
 
Day 63 
<prepopulated date> 
 
 
 
 
Day 64 
<prepopulated date> 
 
 
 
 
Day 65 
<prepopulated date> 
 
 
 
 
Day 66 
<prepopulated date> 
 
 
 
 
Day 67 
<prepopulated date> 
 
 
 
 
Day 68 
<prepopulated date> 
 
 
 
 
Day 69 
<prepopulated date> 
 
 
 
 
Day 70 
<prepopulated date> 
 
 
 
 
Day 71 
<prepopulated date> 
 
 
 
 
Day 72 
<prepopulated date> 
 
 
 
 
Day 73 
<prepopulated date> 
 
 
 
 
Day 74 
<prepopulated date> 
 
 
 
 
Day 75 
<prepopulated date> 
 
 
 
 
Day 76 
<prepopulated date> 
 
 
 
 
Day 77 
<prepopulated date> 
 
 
 
 
Day 78 
<prepopulated date> 
 
 
 
 
Day 79 
<prepopulated date> 
 
 
 
 
Day 80 
<prepopulated date> 
 
 
 
 
Day 81 
<prepopulated date> 
 
 
 
 
Day 82 
<prepopulated date> 
 
 
 
 
Day 83 
<prepopulated date> 
 
 
 
 
Day 84 
<prepopulated date> 
 
 
 
 
 


 
IRB-40947  
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APPENDIX D:  Serious Adverse Event Report Form (Diamond Pharma services) 
 
 

ICF_000.pdf: 
 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 1 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
IRB Use Only 
Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
Are you participating in any other research studies?   _____ Yes   _____No 
INTRODUCTION TO RESEARCH STUDIES 
You are invited to voluntarily participate in a research study of an experimental drug 
called Remetinostat (also known as SHP-141) to treat early stage basal cell carcinomas 
(BCCs).  This study is being conducted by Kavita Sarin, MD, PhD, at the Stanford Cancer 
Center. 
You were selected as a possible participant in this study because you have a 
skin cancer, known as basal cell carcinoma (BCC), and at least 1 lesion (tumor site) is 
5 mm in size or greater (about or more than ⅛ inch), and is being biopsied as a part of 
your regular medical care. 
This document is to be used as a guide for a discussion between you and your 
Study Doctor and the study team.  This form, called an informed consent document, was 
designed to help you understand why this study is being done; what part of the study is 
“research” or “experimental;” what will be asked of you if you choose to participate; 
possible risks; any inconveniences or discomforts you may experience; and other 
important information.  This form may also be helpful as a reference if you choose to 
participate, as a reminder of what your role in the study is, and who to contact if you have 
questions at any time during your participation.  You are urged to discuss any and 
all questions you have about this study with members of the study team.  If you wish, you 
can also discuss this study and your role with your family doctor or medical provider. 
PURPOSE OF RESEARCH 
The study team hopes to learn if there is any beneficial effect of Remetinostat at the 
doses to be used in this study, and if Remetinostat is safe to use at those doses.  
“Phase 2” means the study will include assessments of how well the Remetinostat works 
in treating your cancer.  
The study team hopes to learn if 6 weeks of topical Remetinostat applied 3 times a day 
will slow the growth of BCCs.  We also hope to learn if topical Remetinostat will affect a 
biomarker called “Gli” that is known to be involved in BCC development.  A “biomarker” 
is a biological marker that we can measure to assess a medical condition or disease 
such as BCC.  
It is hoped that Remetinostat could be used in the future to treat or prevent BCCs. 
Your regular medical care for a BCC would include surgical removal of the site of the 
cancer.  The current standard anti-BCC treatment for your lesion includes drugs like 
Efudex (also known as Fluorouracil) and Aldara (also known as Imiquimod).  Using these 
therapies, some patients with BCCs receive treatment benefit, but are not cured of their 
disease.  Your regular medical care would also include skin checks every 3 to 6 months; 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 2 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
IRB Use Only 
Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
biopsies of lesions; and surgical removal of additional BCC lesions as they are identified.  
We are requesting that you delay removal of your BCC lesion by up to 12 weeks while 
you participate in our study.  BCCs are typically slow-growing cancers.  Delaying removal 
by up to 12 weeks should not have a significant effect on your BCC.  Regular medical 
care for BCC would be to schedule the surgery within a week or several weeks.  
The use of Remetinostat in this research study is investigational (“experimental”).  The 
word “investigational” means that Remetinostat is not approved by the US Food and Drug 
Administration (FDA) for use in the United States to treat BCCs.  This study is being 
conducted under an application submitted to FDA, called an “Investigational New Drug 
Application” or “IND.”  
Remetinostat will be provided by the drug manufacturer, Medivir AB. 
If you decide to terminate your participation in this study, you should notify 
Dr. Kavita Sarin at xxx-xxx-xxxx  
This research study is looking for up to 30 people with early stage BCC, of which at least 
10 people are planned to participate in the optional biopsy study.  Stanford University 
expects to enroll research study participants until data on 30 tumors has been collected.  
VOLUNTARY PARTICIPATION  
Your participation in this study is entirely voluntary.  Your decision not to participate will 
not have any negative effect on you or your medical care.  You can decide to participate 
now, but withdraw your consent later and stop being in the study without any loss of 
benefits or medical care to which you are entitled.  
DURATION OF STUDY INVOLVEMENT  
It is planned that each participant will take part in this study for about 8 weeks.  This is a 
2-year study with 6 weeks of active treatment where we will collect medical information 
for each participant.  
PROCEDURES 
It may be harmful to enter this study while receiving some medications; therefore, you will 
be excluded if you are taking certain medications.  Your Study Doctor will review your 
medications and let you know.  
Research studies are usually dividing into at least 3 parts, typically consisting of: 
1. Testing to see if you are eligible to participate in the study (“Screening”);   
2. Testing during study treatment to monitor your health and the effects of the study 
treatment (“Study Evaluation Procedures”); and  


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
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Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
3. Testing after your treatment is complete (“Follow-up”).  Testing/procedures for each 
of these parts are described separately below.  
Some of these examinations, tests, or procedures may be part of your regular medical 
care, and/or and may be done even if you do not join the study.  If you have had some of 
them recently, they may not need to be repeated.  
Before you join this study, Kavita Sarin, MD, PhD, and her research study team will 
review this document with you and ask you to sign this informed consent document.  
After you have signed this document, and received a signed copy, the study will begin 
with a Screening Visit.  
All the procedures listed below are research-related and not part of your regular medical 
care, with the exception of the planned removal of your BCC  at week 8 of the study. 
Screening Visit: 
Location:  The location of the study visits will be at one of the following:  
Stanford Medicine Outpatient Center 
Dermatology Clinic at Portola Valley 
450 Broadway St; Pavilion B 
3240 Alpine Road 
Redwood City, CA  94063 
Portola Valley, CA  94028 
 
Stanford Skin Care Center 
900 Blake Wilbur Drive,  
Palo Alto, CA 94304 
Contact the study team at xxx-xxx-xxxx regarding your Study Visit at any of these 
locations. 
Screening Visit: 
If you choose to participate, the first activity will be “Screening.”  During the 
Screening Visit, you will be asked to have the following tests and activities or 
assessments; 
• The Study Doctor will perform a physical exam to include recording your height, 
weight and vital signs (blood pressure, pulse rate and temperature).  She will 
review your current medications and medical history.  She will also collect some 
general information about you e.g., age; gender; race. 
• You will be asked how well you are able to perform normal daily living activities 
(such as bathing; driving; shopping; working; etc.). 
• A blood sample (2 to 3 teaspoons) may be taken for a serum pregnancy test 
(if you are a woman who can become pregnant).  The pregnancy test must be 
negative within 1 day before the 1st dose of study drug.  
• A serum pregnancy test if you are a woman of child-bearing potential. 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
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Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
The Study Doctor will determine if you are eligible to join the study based on the 
information collected at this visit. 
Women of Childbearing Potential 
If you are pregnant or currently breast-feeding, you may not participate in this study.  It is 
not known whether Remetinostat is safe for the fetus (unborn child) or a breast-fed baby.  
Visit 1: 
• The Study Doctor will go over this consent form and perform a physical exam to 
include recording your weight and vital signs, as described above. 
• You will be asked how well you are able to perform normal daily living activities, as 
described above. 
• She will review your current medications, past medical history 
• Your BCC(s) will be measured and photographed. 
• A small sample of your BCC may be collected, typically by slicing off a small 
piece (a “shave biopsy”), for biomarker testing.  This biopsy is optional.   
Drug treatment: You will be instructed to apply topical 1% Remetinostat to individual 
BCCs 3 times a day for 6 weeks.  You will cover the treated BCCs with a sticky 
strip bandage, such as a Band-Aid. 
Study Drug Application Diary 
You will be provided with a diary to record when you apply the Study Drug. This is 
important because it allows the study team to understand how often participants are 
applying the medication to their cancer(s). You will be asked to fill out this diary for the 
full duration of time you are applying the Study Drug. 
We may contact you weekly by phone to see how you are doing. 
Phone Call (Week 2) 
• Someone from the treatment team will call you to check compliance with medication 
application, drug application method, Adverse Events, and any changes in the 
medications you take.  
Visit 2 (Week 4): 
• The Study Doctor will perform a physical exam to include recording of your 
weight and vital signs, as described above.  
• You will be asked how well you are able to perform normal daily living activities, as 
described above. 
• She will review your current medications and any side effects or symptoms you 
may have experienced with the study drug. 
• Your BCC(s) will be measured and photographed. 
• Your medication diary will be reviewed 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
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Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
Phone Call (Week 6) 
• Someone from the treatment team will call you to check compliance with medication 
application, drug application method, Adverse Events, and any changes in the 
medications you take.  
• You will be reminded to stop the study drug at this time.  
Visit 3 (Week 8): 
• The Study Doctor will perform a physical exam to include recording of your 
weight and vital signs, as described above. 
• You will be asked how well you are able to perform normal daily living activities, as 
described above. 
• She will review your current medications and any side effects or symptoms you 
may have experienced. 
• Your BCC(s) will be measured and photographed. 
• The tumor may be surgically removed at week 8 per regular medical care for 
BCCs. 
• We may temporarily stop or reduce the duration of your treatment if your lesions 
become irritated from the Remetinostat 
• You will apply your last dose of Remetinostat 30 mins before your BCC is 
surgically removed. 
• However, if your surgery has not yet been scheduled, you will be asked to 
continue treatment until your surgery for a maximum of 4 weeks.   
Blood collection:  Blood collection will typically be from a vein in your arm, using a blood 
collection needle.  This is called venipuncture.  Standard clean techniques (“aseptic”) will 
be used.  Your blood samples will not be stored but sent to the Stanford Clinical 
Laboratory.  These samples will be labeled with your name, date of birth and MRN. 
About 2 to 3 teaspoons (10 to 15 mL) of blood will be collected. :  
Tumor biopsy:  A sample of tissue that is taken from your body for laboratory testing, 
such as a sample of your BBC tumor, is called a “biopsy.”  If a screening biopsy is 
collected, a thin slice from the top of the BCC lesion it will cut off with a special cutting 
instrument.  This type of biopsy is called a “shave” biopsy.  No sutures or stiches are 
required after this type of biopsy.  
Tissue Sampling for Laboratory Research Tests  
Research using tissues, such as from your tumor or a blood sample, is an important 
way to try to understand human disease.  A sample of tissue that is taken from your 
body for laboratory testing, such as from skin or a tumor, is called a “biopsy.”  
Biopsy samples of tumor tissue may be taken by cutting out the entire tumor or by taking 
a small sample using a special curved blade.  


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
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Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
 
_____ I consent to optional biopsy for biomarker testing 
 
_____ I do not consent to optional biopsy for biomarker testing 
 
Your tissue samples will be stored in a secure location at Stanford University labeled with 
your initials, date of removal and a unique code number.  Only the Study Doctor and her 
research team will be able to identify you and link your sample to your medical record.  
Analysis on your tissue samples will be conducted at Stanford and/or by the study 
sponsor, Medivir.   
You have the right to refuse to allow your tissues to be studied now or saved for future 
study.  You may withdraw from this study at any time.  The Study Doctors might retain 
the identified samples, eg, as part of your routine clinical care, but not for additional 
research.  
_____ I consent to allow my tissues to be saved for future research 
 
_____ I do not consent to allow my tissues to be saved for future research 
Phone Call (end of study – Week 12): 
You will be contacted by phone to review any residual side effects or symptoms you may 
have experienced. 
Adverse event (or side effects) monitoring will be performed as part of the 
procedures described above.  During the treatment period, the Study Doctors will 
monitor you for any potential side effects.  If the side effects are severe, the 
Study Doctors may withdraw your medication completely.  
If, at any time, you have any symptom; side effect; or injury affecting you physically or 
mentally during the study, you should tell the Study Doctors or nurses right away, 
even if you do not think it was caused by the study medication.  
If you have to go to the hospital for any reason, please tell the hospital staff that you are 
participating on a research study and give them the contact information for the 
study team.  You may be provided with a card with the study team contact information, 
similar to the one represented below.   
 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 7 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
PARTICIPANT RESPONSIBILITIES  
As a participant, your responsibilities include:  
• Follow the instructions of the Study Doctor and study staff. 
• Apply the study drug as instructed. Apply your last dose 30 mins before your 
BCC(s) is surgically removed. 
• Keep your study appointments.  If it is necessary to miss an appointment, please 
contact the Study Doctor or research study staff to reschedule as soon as you 
know you will miss the appointment. 
• Tell the Study Doctor or research study staff about any side effects, doctor visits, 
or hospitalizations that you may have. 
• Tell the Study Doctor or research staff if you believe you might be pregnant or if 
your partner becomes pregnant. 
• Keep the study drug refrigerated and in a safe place, away from children and for 
your use only. 
• Ask questions as you think of them. 
• Tell the Study Doctor or research staff if you change your mind about staying in 
the study. 
Women of Childbearing Potential:  If you are a woman who is able to become 
pregnant, it is expected that you will use an effective method of birth control to prevent 
exposing a fetus to a potentially dangerous agent with unknown risk.  If you are pregnant 
or currently breast feeding, you may not participate in this study.  You understand that if 
you are pregnant, if you become pregnant, or if you are breast-feeding during this study, 
you or your child may be exposed to an unknown risk.  
In order to confirm that you are not pregnant (to the extent medically possible), you agree 
to choose to have a pregnancy test done before beginning this research study.  
You must agree to avoid sexual intercourse or use a birth control method judged to be 
effective by the Study Doctor and which will not interfere with the proposed investigation.  
You must accept the risk that pregnancy could still result despite the responsible use of 
reliable method of birth control.  You agree to notify the Study Doctor as soon as possible 
of any failure of proper use of your birth control method, or if you become pregnant, either 
of which may result in your being withdrawn from the study. 
If you are a man participating in this study and your partner is able to become 
pregnant, you and your partner must use adequate contraception while you are 
participating in the study and for 3 months after stopping treatment.  Your doctor will 
discuss with you what methods of birth control are considered adequate.  You should 
inform your study doctor if your partner becomes pregnant during the study or within 3 
months of stopping treatment. 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 8 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
Your doctor will discuss with you whether your preference for birth control is considered 
adequate.  
WITHDRAWAL FROM THE STUDY 
If you first agree to participate and then you change your mind, you are free to 
withdraw your consent and discontinue your participation at any time.  Your decision will 
not affect your ability to receive medical care for your disease and you will not lose 
any benefits to which you would otherwise be entitled.  
If you decide to withdraw your consent to participate in this study, you should notify 
Dr. Kavita Sarin at xxx-xxx-xxxx .  If you withdraw after starting treatment with the 
study drugs, your Study Doctor will need to check on your health status afterwards.  If 
you do not want the Study Doctor to check on your health status after withdrawing from 
the study, you should say so.  Any information collected before you withdraw will be kept 
and used to complete the research.  
To help you safely finish your participation in the study, the Study Doctors may ask you to 
have more tests and you will be asked to come into the clinic for an 
End-of-Treatment Visit.  The Study Doctor will discuss your treatment options with you at 
this time.  If your participation in the study is ended, you must return all study-related 
supplies, including unused Study Drug.  
The Study Doctor may also withdraw you from the study and the study medication may 
be stopped, without your consent for one or more of the following reasons: 
• Your cancer gets worse.  
• Failure to follow the instructions of the Study Doctor and/or study staff. 
• The Study Doctor decides that continuing your participation could be harmful to 
you. 
• Pregnancy  
• You need treatment not allowed in the study. 
• The study is cancelled.  
• Other administrative reasons. 
• Unanticipated circumstances. 
After you finish the study or stop taking the Study Drug for any other reason, you may 
continue to be checked regularly (physical exams; blood tests; tumor measurements; 
X-rays; other scans, etc.) if you continue to have significant side effects from the 
treatment.  This is called follow-up.  Your Study Doctor will follow your progress, in 
accordance with good medical care, for as long as it is felt to be necessary by both you 
and the Study Doctor, unless you ask otherwise.  Many if not all of these procedures will 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 9 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
be part of your regular continued medical care.  In addition, further treatment outside the 
study will be discussed with you.  
POSSIBLE RISKS, DISCOMFORTS, AND INCONVENIENCES  
There are risks, discomforts, and inconveniences associated with any research study.  
These deserve careful thought.  You should talk with the Study Doctor if you have any 
questions. 
Risks from Remetinostat (SHP-141) 
The main remetinostat treatment-related AEs were skin findings including 
irritation, dermatitis, erythema, dry skin, rash, exfoliation, skin lesion, 
inflammation, pain, paraesthesia, erythema, pruritus, infection, application site 
reaction, skin papilloma which resolved on reducing the frequency of remetinostat 
application or stopping application for short periods of up to 2 weeks. 
The effect of Remetinostat in pregnancy has not been studied.  Similarly, 
excretion of Remetinostat into breast milk has not been examined.  Therefore, 
pregnant and lactating women are excluded from clinical trials at this time.  
Risks from Topical Treatments 
Many drugs that are administered topically can cause irritation and/or 
inflammation of the skin.  This may be due to the ingredients the drug is mixed in, 
or the drug itself. 
Allergic reactions 
Sometimes people have allergic reactions to drugs.  Although unlikely, especially 
for an application to a small area of skin, if you have a very bad allergic reaction, 
you could die.  Some things that happen during an allergic reaction that could be 
a sign or symptom of a life-threatening allergic reaction (anaphylaxis) are: 
• 
Rash 
• 
Having a hard time breathing (shortness of breath) 
• 
Wheezing when you breathe 
• 
Sudden drop in blood pressure 
• 
Swelling around the mouth, throat, or eyes 
• 
Fast pulse 
• 
Sweating 
You should get medical help and notify the Study Doctor or study staff if you 
experience any of these or any other side effects during the study. 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 10 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
Risks of giving blood (venipuncture) 
The Study Doctor or study staff will take your blood by sticking a needle in your 
arm.  Some problems you might have from this are pain, bruising, dizziness and 
infection.  
Risks for Women of Childbearing Potential 
If you are a woman, you cannot be in this study if you are pregnant.  Woman 
should not breastfeed a baby while in this study.  You must not become pregnant 
during the study or within 3 months of stopping treatment. 
If you are pregnant or nursing while receiving Remetinostat, there may be risks to 
the fetus or nursing child.  Nobody knows what these risks are right now.  Some 
drugs cause premature (early) birth or birth defects. 
All historically documented and confirmed post-menopausal women (women who 
no longer have menstrual periods), surgically sterile women, or women using a 
medically acceptable form of birth control will be considered for participation in the 
study.  All women who can have children will have a serum pregnancy test as part 
of the screening visit.  If you have a positive pregnancy test, you will not be able to 
enter in the study. 
The only certain way to prevent pregnancy is to not have sex.  If you are a woman 
who can have children, the study staff will talk to you about birth control you must 
use during the study.  
Even if you use a medically proven birth control method, there is a chance you 
could still become pregnant.  Some types of birth control will not work when you 
are taking certain drugs. 
If you think you are pregnant during the study or become pregnant within 3 months of 
stopping treatment, you must tell the Study Doctor immediately. Women who become 
pregnant during the study will have to leave the study.  If you become pregnant, you 
will be removed from the study. The study doctor or study staff may ask for information 
about the pregnancy and the birth of the baby.  The study doctor will share this 
information with the sponsor and the IRB (a group of people who review research 
studies to protect the rights and welfare of research participants). 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 11 of 18 
 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
POTENTIAL BENEFITS  
Use of Remetinostat (SHP-141) is this study may help reduce your BCC lesion(s).  It is 
not known whether being in this study will help you, since Remetinostat (SHP-141) has 
not been used in treatment of BCC before.  Your BCC might not get better or may even 
get worse while you are in the study.  However, information from this study might help 
researchers determine how to treat BCC patients in the future. 
We cannot and do not guarantee or promise that you will receive any benefits from this 
study.  
ALTERNATIVES 
You do not have to be in this study to receive treatment for your cancer.  Instead of taking 
part in this study, you may choose to receive treatment with other cancer drugs or have 
immediate surgical treatment.  Your study doctor will discuss the risks and benefits of 
other treatments with you.  
The Study Doctors will discuss with you the risks and benefits of these alternatives, 
including which other treatments might be suitable for you.  
If you decide that you do not wish to take part in this study and wish to pursue any of 
these, or other alternatives, this will not change your regular medical care or the other 
treatment choices in any way.  
PARTICIPANT’S RIGHTS 
You should not feel obligated to agree to participate.  Your questions should be answered 
clearly and to your satisfaction.  
If you decide not to participate, tell the Study Doctor.  You will still receive care for your 
disease and will not lose any benefits to which you would otherwise be entitled. 
You will be told of any significant new information that is learned during the course of this 
research study, which might affect your condition or your willingness to continue 
participation in this study.  After you hear about this information, you have the right to 
withdraw from the program.  
ClinicalTrials.gov 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by US Law.  This web site will not include information that can identify you.  
At most, the web site will include a summary of the results.  You can search this 
web site at any time.  


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 12 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
IRB Use Only 
Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
CONFIDENTIALITY 
The results of this research study may be presented at scientific or medical meetings or 
published in scientific journals.  Your identity and/or your personal health information will 
not be disclosed except as authorized by you or as required by law.  However, there is 
always some risk that even de-identified information might be re-identified.  
Patient information may be provided to Federal and other regulatory agencies 
as required.  The US FDA, for example, may inspect research records and learn your 
identity if this study falls within its jurisdiction.  
The purpose of this research study is to obtain data or information on the safety and 
effectiveness of Remetinostat; the results will be provided to the sponsor, the Food and 
Drug Administration and other federal and regulatory agencies as required. 
CERTIFICATE OF CONFIDENTIALITY 
This research is covered by a Certificate of Confidentiality from the National Institutes 
of Health. The researchers with this Certificate may not disclose or use information, 
documents, or biospecimens that may identify you in any federal, state, or local civil, 
criminal, administrative, legislative, or other action, suit, or proceeding, or be used as 
evidence, for example, if there is a court subpoena, unless you have consented for this 
use. Information, documents, or biospecimens protected by this Certificate cannot be 
disclosed to anyone else who is not connected with the research except, if there is a 
federal, state, or local law that requires disclosure (such as to report child abuse or 
communicable diseases but not for federal, state, or local civil, criminal, administrative, 
legislative, or other proceedings, see below); if you have consented to the disclosure, 
including for your medical treatment; or if it is used for other scientific research, as 
allowed by federal regulations protecting research subjects. 
 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 13 of 18 
 
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IRB Use Only 
Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
Authorization To Use Your Health Information  
For Research Purposes 
Because information about you and your health is personal and private, it 
generally cannot be used in this research study without your written 
authorization.  If you sign this form, it will provide that authorization.  The 
form is intended to inform you about how your health information will be 
used or disclosed in the study.  Your information will only be used in 
accordance with this authorization form and the informed consent form and 
as required or allowed by law.  Please read it carefully before signing it.  
 
What is the purpose of this research study and how will my health 
information be utilized in the study?  
The primary purpose of this study is to determine if 6 weeks of topical 
Remetinostat applied three times daily will suppress Basal Cell Carcinoma.  
If you choose to participate, the study staff will obtain personal information 
about you for research purposes. This may include medical and research 
records that may identify you and that may describe your health. The Study 
Doctor and research staff may obtain and give out records about your study 
visits, physical exams, medical history, telephone calls, laboratory results, 
other test results and response to study treatment including side effects, 
medications, and study drug you received. 
 
Do I have to sign this authorization form? 
You do not have to sign this authorization form.  But if you do not, you will 
not be able to participate in this research study including receiving any 
research-related treatment.  Signing the form is not a condition for receiving 
any medical care outside the study.  
 
If I sign, can I revoke it or withdraw from the research later?  
If you decide to participate, you are free to withdraw your authorization 
regarding the use and disclosure of your health information (and to 
discontinue any other participation in the study) at any time.  After any 
revocation, your health information will no longer be used or disclosed in 
the study, except to the extent that the law allows us to continue using your 
information (eg, necessary to maintain integrity of research).  If you wish to 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 14 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
IRB Use Only 
Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
revoke your authorization for the research use or disclosure of your health 
information in this study, you must write to:  
Kavita Sarin, MD, PhD 
Dermatology - North Campus  
450 Broadway St  
 
Redwood City, CA  94063  
 
What Personal Information Will Be Obtained, Used or Disclosed?  
Your health information related to this study may be used or disclosed in 
connection with this research study, including, but not limited to information 
related to your medical condition, blood tests, pathology, EKG, physical 
exam, current medications, side effects, and photos of lesions and medical 
imaging results.  The researchers will also get information from your 
medical record (including hospital records from the Stanford Healthcare 
and your referring physician’s records).  
 
Who May Use or Disclose the Information?  
The following parties are authorized to use and/or disclose your health 
information in connection with this research study:  
• The Study Doctor, Kavita Sarin, MD, PhD 
• Research Staff 
• The Stanford University Administrative Panel on Human Subjects in 
Medical Research; the Stanford Data and Safety Monitoring 
Committee (DSMC); and/or any other unit of Stanford University as 
necessary 
 
Who May Receive or Use the Information? 
The parties listed in the preceding paragraph may disclose your health 
information to the following persons and organizations for their use in 
connection with this research study:  
• Medivir AB or their representatives 
• The American Skin Association 
• The Food and Drug Administration (FDA) and/or other state or 
international regulatory authorities  


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
• The Office for Human Research Protections (OHRP) in the 
US Department of Health and Human Services (DHHS) 
Your information may be re-disclosed by the recipients described above, if 
they are not required by law to protect the privacy of the information.  
 
When will my authorization expire? 
Your authorization for the use and/or disclosure of your health information 
will end on 31 December 2032 or when the research project ends, 
whichever is earlier.  
 
Will access to my medical record be limited during the study? 
To maintain the integrity of this research study, you may not have access to 
any health information developed as part of this study until it is completed.  
At that point, you would have access to such health information if it was 
used to make a medical or billing decision about you (eg, if included in your 
official medical record).  
 
___________________________________________ 
____________  
Signature of Adult Participant  
 
 Date 
___________________________________________ 
Printed Name of Adult Participant  
 
 
NOTE:  If using the Short Form Consent process for informed consent in another 
language pursuant to an "Alteration of HIPAA Authorization," the participant should not 
sign the HIPAA “Authorization To Use Your Health Information For Research Purposes” 
above.  


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
Page 16 of 18 
 
Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
IRB Use Only 
Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
FINANCIAL CONSIDERATIONS 
Costs 
If you participate in this study, the study will pay for those services, supplies, procedures, 
and care associated with this study that are not a part of your routine medical care.  
However, there may be additional costs to you.  These include basic expenses like 
transportation and the personal time it will take to come to the Study Visits.   
You and/or your health insurance must pay for services, supplies, procedures, and care 
that are required during this study for routine medical care.  You will also be 
responsible for any co-payments and/or deductibles as required by your 
insurance.  Participation in this study is not a substitute for health insurance.   
Payments  
You will not be paid to participate in this research study.  There is no reimbursement 
offered for any expenses related to your participation in this study.  
Funding Source  
This study is funded in part by Medivir, AB, the company who owns the study drug 
Remetinostat. The Stanford Dermatology Department is also partially funding this study. 
The National Institutes of Health are providing additional financial support for this study. 
Consultative or Financial Relationships  
None  
COMPENSATION for Research-Related Injury 
All forms of medical diagnosis and treatment – whether routine or experimental – 
involve some risk of injury.  In spite of all precautions, you might develop 
medical complications from participating in this study.  If such complications arise, the 
Study Doctor and the research study team will assist you in obtaining appropriate 
medical treatment.  In the event that you have an injury or illness that is directly caused 
by your participation in this study, reimbursement for all related costs of care first will be 
sought from your insurer, managed care plan, or other benefits program. If costs of care 
related to such an injury are not covered by your insurer, managed care plan or other 
benefits program, you may be responsible for these costs.  If you are unable to pay for 
such costs, the Study Doctor will assist you in applying for supplemental benefits and 
explain how to apply for patient financial assistance from the hospital. You will be 
responsible for any associated co-payments or deductibles as required by 
your insurance.  
You do not waive any liability rights for personal injury by signing this form. 


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
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Topical Reminostat on BCC/ Dr Kavita Sarin / IRB-40947 ICF version 23 March 2020 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
CONTACT INFORMATION  
Questions, Concerns, Complaints, or to Report an Injury or Side Effect:  If you 
have any questions, concerns or complaints about this research study, its procedures, 
risks and benefits, or alternative courses of treatment, you should ask the Study Doctor, 
Kavita Sarin, MD, PhD, at xxx-xxx-xxxx.You should also contact her at any time if you 
feel you have been hurt by being a part of this study.  
If you are unable to reach anyone at the number(s) listed above, and you feel you may 
need medical attention, call or go to the nearest emergency room.  
Independent Contact:  If you are not satisfied with how this study is being conducted, 
or if you have any concerns, complaints, or general questions about the research or 
your rights as a participant, please contact the Stanford Institutional Review Board (IRB) 
to speak to someone independent of the research team at xxx-xxx-xxxx or toll-free at 
1-xxx-xxx-xxxx .  You can also write to the Stanford IRB, Stanford University, 
1705 El Camino Real, Palo Alto, CA 94306. 
Alternate Contact:  If you cannot reach the Study Doctor, please contact study 
coordinator at xxx-xxx-xxxx 
EXPERIMENTAL SUBJECT’S BILL OF RIGHTS 
As a research participant you have the following rights.  These rights include but are 
not limited to the participant's right to:  
• 
Be informed of the nature and purpose of the experiment;  
• 
Be given an explanation of the procedures to be followed in the 
medical experiment, and any drug or device to be utilized;  
• 
Be given a description of any attendant discomforts and risks reasonably 
expected;  
• 
Be given an explanation of any benefits to the subject reasonably to be expected, 
if applicable;  
• 
Be given a disclosure of any appropriate alternatives, drugs or devices that might 
be advantageous to the subject, their relative risks and benefits;  
• 
Be informed of the avenues of medical treatment, if any available to the subject 
after the experiment if complications should arise;  
• 
Be given an opportunity to ask questions concerning the experiment or the 
procedures involved;  
• 
Be instructed that consent to participate in the medical experiment may be 
withdrawn at any time and the subject may discontinue participation without 
prejudice;  


 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Kavita Sarin, MD, PhD           
Protocol Title:   
A Phase 2 Open label, Single arm Trial to Investigate the Efficacy and Safety of Topical 
Remetinostat Gel as Neoadjuvant Therapy in Patients Undergoing Surgical Resection of 
Basal Cell Carcinoma (BCC) 
 
 
 
 
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Approval Date:   April 15, 2020 
Expiration Date: April 15, 2021 
Participant ID: 
• 
Be given a copy of the signed and dated consent form; and  
• 
Be given the opportunity to decide to consent or not to consent to a medical 
experiment without the intervention of any element of force, fraud, deceit, duress, 
coercion or undue influence on the subject's decision.  
 
Signing your name means you agree to be in this study and that you will receive a 
copy of this signed and dated consent form.  
 
_______________________________________________ 
____________  
Signature of Adult Participant 
 Date 
 
_______________________________________________ 
Printed Name of Adult Participant 
 
  
_______________________________________________ 
_____________ 
Signature of Person Obtaining Consent (POC) 
 Date  
 
_______________________________________________ 
  
Printed Name of POC 
   
 
The following witness line is to be signed only if the consent is provided as a summary form and 
accompanied by a short-form foreign language informed consent document. 
 
_______________________________________________ 
____________  
Signature of witness 
       Date 
_______________________________________________ 
Printed name of witness 
(eg, staff, translator/interpreter, family member)  
The translated short form must be signed and dated by BOTH the participant AND the witness.  
The English consent form (“referred to as the "Summary Form" in the regulations”):  
• 
Must be signed by BOTH the witness AND the Person Obtaining Consent (POC).  
• 
The non-English speaking participant does NOT sign the English consent.  
• 
The non-English speaking participant should NOT sign the HIPAA participant line.  
• 
If the participant is non-English speaking, the POC must ensure that any questions or  
options presented by the consent form are documented and initialed by the POC on the  
Summary Form, per the participant's wishes, as they are understood during the consent     
process.