Clinical trial NCT04862585
Conditions: Anatomic Stage 0 Breast Cancer AJCC v8 Anatomic Stage I Breast Cancer AJCC v8 Anatomic Stage IA Breast Cancer AJCC v8 Anatomic Stage IB Breast Cancer AJCC v8 Anatomic Stage II Breast Cancer AJCC v8 Anatomic Stage IIA Breast Cancer AJCC v8 Anatomic Stage IIB Breast Cancer AJCC v8 Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IIIA Breast Cancer AJCC v8 Anatomic Stage IIIB Breast Cancer AJCC v8 Anatomic Stage IIIC Breast Cancer AJCC v8 Anatomic Stage IV Breast Cancer AJCC v8 Breast Carcinoma Prognostic Stage 0 Breast Cancer AJCC v8 Prognostic Stage I Breast Cancer AJCC v8 Prognostic Stage IA Breast Cancer AJCC v8 Prognostic Stage IB Breast Cancer AJCC v8 Prognostic Stage II Breast Cancer AJCC v8 Prognostic Stage IIA Breast Cancer AJCC v8 Prognostic Stage IIB Breast Cancer AJCC v8 Prognostic Stage III Breast Cancer AJCC v8 Prognostic Stage IIIA Breast Cancer AJCC v8 Prognostic Stage IIIB Breast Cancer AJCC v8 Prognostic Stage IIIC Breast Cancer AJCC v8 Prognostic Stage IV Breast Cancer AJCC v8
Sponsor: Ohio State University Comprehensive Cancer Center
Start date: 2021-10-07; Completion date: 2024-06-21
Enrollment: 130 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase II/III trial investigates the difference in rates of infusion hypersensitivity reaction in patients with breast cancer who are receiving paclitaxel alone or in combination with other cancer drugs which require parenteral rescue medication after stopping standard pre-medications (dexamethasone, diphenhydramine, famotidine/cimetidine/ranitidine), compared to continuing premedications. Paclitaxel is a drug used to treat breast cancer, ovarian cancer, and autoimmune deficiency syndrome (AIDS)-related Kaposi sarcoma. It blocks cell growth by stopping cell division and may kill cancer cells. It is a type of antimitotic agent. However, there are side-effects and toxicities associated with repeat exposure to this pre-medication regimen. With prolonged use of paclitaxel, especially during weekly regimens, patients are exposed to repeat doses of drugs that prevent hypersensitivity reactions. Side effects include, but are not limited to, insomnia, gastritis, fluid retention, weight gain, mood changes and immune suppression. The information gained from this study may positively influence clinical practice and help researchers develop methods to safely stop pre-medications.

Detailed description:
PRIMARY OBJECTIVE:

I. To estimate the difference in rates of infusion hypersensitivity reaction (HSR) requiring parenteral rescue medications following the discontinuation of pre-medications after 2 doses of paclitaxel, compared to continuing premedications, in breast cancer patients who have not experienced an infusion HSR with their first 2 paclitaxel doses.

OUTLINE:

Patients receive paclitaxel per standard of care as a single agent or in combination with dexamethasone intravenously (IV) and/or orally (PO), diphenhydramine IV and/or PO and either famotidine IV and/or PO, ranitidine IV and/or PO or cimetidine IV and/or PO. Patients who don't experience any infusion hypersensitivity reaction after the first 2 doses of paclitaxel are randomized to 1 of 2 arms.

ARM I (STANDARD OF CARE): Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.

ARM II (EXPERIMENTAL): Patients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.

Arms: arm 1: Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel. arm 2: Patients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.
Interventions: intervention 1: Cimetidine intervention 2: Dexamethasone intervention 3: Diphenhydramine intervention 4: Famotidine intervention 5: Paclitaxel intervention 6: Quality-of-Life Assessment intervention 7: Ranitidine
Intervention descriptions: intervention 1: Given IV and/or PO intervention 2: Given IV and/or PO intervention 3: Given IV and/or PO intervention 4: Given IV and/or PO intervention 5: Weekly or every 14 day dosing intervention 6: Ancillary studies intervention 7: Given IV and/or PO

Protocol documents:
Prot_SAP_000.pdf: 
1 
V6_6/9/2023 
 
Safely Stopping Pre-medications in Patients Receiving Paclitaxel: A Randomized Trial 
 
 
Study Chair: 
Michael Berger, Pharm D 
Institution: Ohio State University Wexner Medical Center 
Address: 1145 Olentangy River Road, Columbus, OH, 43212 
Phone: 614-366-0556 
Fax: 614-293-1943 
Email: Michael.Berger@osumc.edu 
 
Co-Chair: 
Charles Loprinzi, MD 
Institution: Mayo Clinic 
Address: 200 First Street Southwest, Rochester, MN, 55905 
Phone: 507-538-3270 
Fax: 507-538-7802 
Email: Cloprinzi@mayo.edu 
 
Primary Statistician: 
Paul J Novotny, MS 
Institution: Mayo Clinic 
Address: 200 First Street Southwest, Rochester, MN, 55905 
Phone: 507-284-4186 
Fax: 507-266-2477 
Email: novotny@mayo.edu 


2 
V6_6/9/2023 
 
Study Schema: 
 
 
 
 
 
 
 
RANDOMIZE 
 
 
 
 
 
 
 
 
 
 
 
 
Stratification Factors 
• Weekly paclitaxel vs every 14-day paclitaxel dosing 
• Hypersensitivity premedication regimen 
Evaluate for difference in parenteral rescue medication use for 
grade 2 or greater infusion HSR with subsequent paclitaxel doses 
(a measure of clinically significant infusion hypersensitivity) 
Breast cancer patients initiating paclitaxel 
therapy are enrolled on trial 
If no infusion hypersensitivity reaction (HSR) 
with first 2 doses of paclitaxel: 
Standard of care: 
Continue pre-medications with 
all future doses of paclitaxel 
Experimental: 
Discontinue premedications with all 
future doses of paclitaxel, unless patient 
develops a subsequent infusion HSR 


3 
V6_6/9/2023 
 
Table of Contents 
1.0 Objective .................................................................................................................................. 4 
2.0 Background and Rationale ..................................................................................................... 4 
3.0 Eligibility 
3.1 Inclusion Criteria ................................................................................................................. 6 
3.2 Exclusion Criteria ................................................................................................................ 7 
4.0 Study Design and Methods 
4.1 Patient identification and recruitment ................................................................................. 7 
4.2 Protection of patient rights and confidentiality ................................................................... 7 
4.3 Data collection ..................................................................................................................... 8 
4.4 Study design ......................................................................................................................... 9 
4.5 Endpoints .............................................................................................................................. 9 
4.6 Stratification factors definition and justification .................................................................. 10 
5.0 Treatment Plan ......................................................................................................................... 10 
5.0 Study calendar ...................................................................................................................... 10 
5.1 Premedication treatment plan ............................................................................................... 11 
5.2 Rescue medication treatment plan… ..................................................................................... 13 
6.0 Statistical Considerations ........................................................................................................ 14 
6.1 Sample size justifications ..................................................................................................... 14 
6.2 Accrual time ......................................................................................................................... 14 
6.3 Analysis plan ........................................................................................................................ 15 
7.0 Measurement / Instrumentation ............................................................................................. 16 
7.1 Hypersensitivity assessment ................................................................................................... 16 
7.2 Overall quality of life (QOL) measurement and symptom experience evaluation ................ 17 
8.0 Adverse Events Reporting ....................................................................................................... 17 
8.1 Adverse event reporting ....................................................................................................... 17 
8.2 Serious adverse events ......................................................................................................... 17 
Appendix I - NCI Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0: 
Infusion Related Reaction ........................................................................................................... 19 
9.0 References .............................................................................................................................. 20 


4 
V6_6/9/2023 
 
1.0 Objective 
 
The goal of this study is to estimate the difference in rates of infusion hypersensitivity reaction (HSR) requiring 
parenteral rescue medications following the discontinuation of pre-medications after 2 doses of paclitaxel, 
compared to continuing premedications, in breast cancer patients who have not experienced an infusion HSR with 
their first 2 paclitaxel doses. 
 
2.0 Background and Rationale 
 
Paclitaxel is commonly used in a variety of solid tumors, including breast cancer. Due to its hydrophobic 
properties, paclitaxel is emulsified in polyoxyethylated castor oil (Cremophor El) and ethanol. Paclitaxel 
(particularly, its solvent cremophor) is known to cause infusion hypersensitivity reactions (HSR). Therefore, 
patients have been routinely pre-medicated with a steroid (dexamethasone), an H1 antagonist (diphenhydramine), 
and a H2 antagonist (e.g., famotidine or ranitidine) for HSR prophylaxis before paclitaxel infusions, to mitigate 
or minimize the severity of the reaction. In early published clinical studies, all grade hypersensitivity reactions 
occurred in 41% of patients (prior to routine use of premedications) and grade 3 or higher reactions occurred in 
2% of patients with the use of a standard pre-medication regimen.1 Similar grade 3 reaction rates of less than 3% 
have been reported in patients with breast cancer receiving weekly paclitaxel. 
 
However, there are side-effects and toxicities associated with repeat exposure to this pre-medication regimen. The 
most frequently used corticosteroid in the prevention of paclitaxel-induced hypersensitivity reactions is 
dexamethasone, which is among the most potent and long acting of the corticosteroids. With prolonged use of 
paclitaxel, especially during weekly regimens, patients are exposed to repeat doses of dexamethasone. Side- 
effects include, but are not limited to, insomnia, gastritis, fluid retention, weight gain, mood changes and immune 
suppression.2 Furthermore, the use of parenteral diphenhydramine is commonly associated with drowsiness and 
can paradoxically cause dystonia and restlessness.3 
 
In addition to short term toxicities, use of steroids along with chemotherapy has been associated with potentially 
increased risk of hyperglycemia, metabolic syndrome, and type II diabetes mellitus. Chemotherapy has been 
reported to have varying effects on markers of glucose regulation.4-7 In an observational study of 963 breast cancer 
patients undergoing chemotherapy, without diagnosed metabolic syndrome or diabetes at baseline, researchers 
reported that dysregulated glucose metabolism was exacerbated by chemotherapy4. Over 70% of women met 
criteria for metabolic syndrome after four months of chemotherapy. This is a critical problem, considering that 
metabolic syndrome increases risk for co-morbidities such as cardiovascular disease and diabetes8 and is 
associated with increased mortality in women with breast cancer 9. Although the mechanism by which 
chemotherapy induces deterioration in glucose metabolism is not completely clear, several studies have postulated 
that weight gain associated with chemotherapy treatment for breast cancer, promotes development of 
inflammation and insulin resistant.10,11 Use of steroids can further exacerbate chemotherapy-associated metabolic 
effects.12 Steroids, in combination with chemotherapy, can have profound effects on glucose and insulin.12,13 
These findings may negatively impact clinical outcomes, since increasing insulin levels and insulin resistance are 
associated with increased recurrence of breast cancer 13 and increased risk of distance recurrence14. 
 
A growing body of published data suggests that, if a patient has not experienced an infusion HSR after 2 doses of 
paclitaxel, the chances of having an infusion HSR reaction with future doses is remote. A prospective single arm 
study was conducted at the Stefanie Spielman Comprehensive Breast Center (SSCBC), Columbus, OH. Seventy 
patients with stage I-IV breast cancer receiving paclitaxel therapy were enrolled on this trial from August 2009 
to March 2010.15 Fifty-five patients who did not experience a paclitaxel infusion HSR with first 2 doses had all 


5 
V6_6/9/2023 
 
pre-medications stopped for future doses and were eligible for primary analysis. The incidence of rescue 
medication use to treat an infusion HSR in these 55 patients was 0% (CI 0-5.4%).15 
 
After the publication of this feasibility study, practice patterns changed at SSCBC; patients with breast cancer 
who had not experienced an infusion HSR after 2 doses of paclitaxel, and who wished to stop receiving paclitaxel 
pre-medications due to side effects, were commonly permitted to discontinue pre-medications prior to the 3rd and 
all future paclitaxel doses. 
 
To evaluate this practice change, SSCBC investigators retrospectively reviewed practice patterns between January 
2011 and June 2013. During this time period 449 patients were treated with various schedules of paclitaxel and 
paclitaxel-containing regimens at the SSCBC. Patients were identified through electronic medical record review. 
The rationale for doing this retrospective study was to assess the use of rescue medications to treat infusion HSR 
for paclitaxel doses 3 through 6 after the pre-medications were removed following 2 doses of paclitaxel in patients 
who had not experienced a prior HSR reaction, to better validate our previous findings in a larger population of 
patients.16 
 
Included in this study were patients ≥18 years old who were scheduled to receive at least four doses of paclitaxel 
as a single chemotherapy agent or in combination with trastuzumab, bevacizumab, gemcitabine, or other drug 
combinations (excluding cisplatin or carboplatin) for treatment of any stage breast cancer. Patients with chronic 
medical conditions were allowed in both the prospective and retrospective studies at the SSCBC. Other exclusion 
criteria included patients who received therapy with a taxane in the previous 12 months, patients in whom 
paclitaxel was discontinued or changed to a different taxane after 1-2 doses, patients who did not receive premeds 
with their first 2 doses of paclitaxel and any pre-medications added back into the plan after being removed 
previously, unless the reason for doing this was from evidence of a paclitaxel–infusion reaction that occurred 
without premedications. 
 
Of 449 eligible patients, 234 (52.1%) patients met inclusion criteria, while 215 (47.9%) were excluded. Only two 
of 234 patients (0.8%) required rescue medication to treat a paclitaxel infusion HSR after pre-medications were 
removed following the 2nd dose of paclitaxel. These results further demonstrated the safety and feasibility of 
discontinuing pre-medications after 2 doses of paclitaxel in patients who had not experienced a prior HSR 
reaction. 
 
Other authors have also reported confirmatory findings. Parinyanitikul N et al. recently published a retrospective 
study of Asian women receiving weekly paclitaxel 80 mg/m2 for early stage breast cancer.17 Patients received 
dexamethasone 5 mg IV, diphenhydramine 25 mg IV and ranitidine 50 mg IV pre-medications; if no infusion 
HSR was seen after the first 2 doses, the dexamethasone was discontinued (the diphenhydramine and ranitidine 
were continued) for doses 3 through 12. The incidence of HSR in patients who omitted dexamethasone was 6.25% 
(5 of 81 patients). The authors reported all of these patients were able to be successfully re-challenged with 
paclitaxel. 
 
Additionally, de Castro Baccarin AL et al. published a small prospective study in women receiving weekly 
paclitaxel 80 mg/m2 for early stage breast cancer.18 Patients received dexamethasone 20 mg IV, diphenhydramine 
50 mg IV and ranitidine 50 mg IV pre-medications; if no infusion HSR was seen after the first 2 doses, the 
dexamethasone was discontinued (the diphenhydramine and ranitidine were continued) for doses 3 through 12. 
The incidence of HSR in patients who omitted dexamethasone was 0% (0 of 25 patients). 
 
It is worth noting that the incidence of infusion HSR and subsequent use of rescue medication in patients who 
continue to receive pre-medications beyond the 2nd dose and beyond, has not been published, to our knowledge. 


6 
V6_6/9/2023 
 
But, in order to gain insight into this question, we conducted a retrospective chart review of female patients 
receiving weekly paclitaxel at SSCBC between 2015 and 2020. Patients with any stage breast cancer who had not 
previously received paclitaxel, and who did NOT have an infusion HSR with their first 2 doses, and who continued 
premedications aimed at preventing paclitaxel reactions, were examined. Of the first 75 consecutive patients who 
met this criteria, 3 patients (4%) experienced an infusion HSR that required rescue medication in doses 3 through 
12 of paclitaxel. 
 
The above data raise the question of whether it is reasonable to conduct a randomized clinical trial to obtain high- 
quality evidence to support the discontinuation of pre-medications after 2 doses of paclitaxel compared to 
continuing pre-medications, which is the standard of care supported by the FDA label for paclitaxel. This is what 
we will evaluate in this proposed study. 
 
This study is not researching the discontinuation of premeds prior to other taxanes such as docetaxel or cabazitaxel 
as these drugs may have different premedication requirements and are formulated with a different surfactant than 
conventional paclitaxel. Paclitaxel albumin-bound, because it is formulated with human albumin and does not 
contain a surfactant, does not routinely cause infusion hypersensitivity, and therefore has no premedication 
requirements and will not be included in this research. 
 
If the results of this trial illustrate that the premedications prior to conventional paclitaxel are deemed 
unnecessary, this should markedly influence clinical practice by reducing chemotherapy administration time, 
lowering health care costs, decreasing diphenhydramine-induced drowsiness, and decreasing steroid-related 
toxicities such as agitation, insomnia, bone loss, altered glucose metabolism, and weight gain. 
 
3.0 Eligibility 
 
3.1 Inclusion criteria 
 
3.1.1 Female or male patients scheduled to receive at least 4 doses of weekly paclitaxel 80 mg/m2 or “dose 
dense paclitaxel” 175 mg/m2 every 14 days, as a single-agent or in combination with trastuzumab, 
pertuzumab, bevacizumab, pembrolizumab, lapatinib, gemcitabine or other drug combination 
(excluding cisplatin or carboplatin) for the treatment of any stage, histologically confirmed breast 
cancer 
 
3.1.2 Ability to complete questionnaires by themselves or with assistance 
 
3.1.3 Life expectancy ≥ 6 months 
 
3.1.4 ECOG performance status 0-2 
 
3.1.5 Age >18 
 
3.1.6 Able to give informed consent 
 
3.1.7 In accordance with standard of care and FDA labeling for paclitaxel, patients must be scheduled to 
receive prophylactic HSR premedications (IV or oral) consisting of diphenhydramine or cetirizine ( 
histamine-1 (H1) antagonists), dexamethasone (a steroid) and either famotidine, ranitidine, or 
cimetidine (histamine-2 (H2) antagonists), per institutional guidelines, prior to each of their first 2 
doses of paclitaxel. 


7 
V6_6/9/2023 
 
3.1.8 Patients may enroll, or currently be enrolled in another concurrent clinical trial, including trials with 
investigational drugs given in combination with paclitaxel, provided the other trial would not prohibit 
the discontinuation of paclitaxel premedications, and provided the trial would allow for paclitaxel to 
be administered first in order of infusion. 
 
3.1.9 Intermittent oral steroids for nausea or for acute inflammatory conditions (i.e. methylprednisolone 
dosepak) and inhaled, intranasal or topical corticosteroids are permitted. 
 
 
3.2 Exclusion criteria 
 
3.2.1 Patients who have received at least 1 prior lifetime dose of paclitaxel or paclitaxel albumin-bound. 
(Patients may have received prior lifetime doses of docetaxel or cabazitaxel.) 
 
3.2.2 Patients receiving paclitaxel in combination with carboplatin or cisplatin (due to risk of 
hypersensitivity with platinum compounds) 
 
3.2.3 History of grade 3 hypersensitivity reaction to cremophor EL containing medications (e.g. paclitaxel, 
cyclosporine, ixabepilone, teniposide) 
 
3.2.4 Patients receiving therapeutic daily doses of systemic corticosteroids. 
 
3.2.5 Patients who are pregnant or nursing. Paclitaxel is classified by the FDA as “pregnancy category D”. 
Pregnancy testing (urine or blood Hcg) will be done and documented prior to enrollment if pregnancy 
is clinically suspected. 
 
4.0 Study Design and Methods 
 
4.1 Patient identification and recruitment: 
 
Patients with breast cancer who meet eligibility criteria will be recruited in medical oncology clinics at the 
Stefanie Spielman Comprehensive Breast Center (SSCBC) of the The James Cancer Hospital at The 
OSUWMC. After study implementation, the investigators hope to open this trial at additional sites, possibly 
including the medical oncology clinics from the Minnesota Cancer Clinical Trials Network (MNCCTN) and 
OSU James Network participating sites. Based upon data obtained from our SSCBC breast medical oncology 
clinic, there are approximately 2 to 3 patients beginning paclitaxel or paclitaxel-based chemotherapy each 
week. Some of these patients will be receiving paclitaxel in combination with cisplatin or carboplatin, or may 
currently be enrolled in another trial that may prohibit changing premedications, and therefore excluded. 
Estimated duration of the study, based upon projected enrollment of 5-7 eligible patients per month across 
multiple sites, should be about 18-24 months. 
 
Patients will be screened for eligibility during routine clinic visits by a clinical research coordinator, physician, 
medical oncology fellow, nurse practitioner, nurse or pharmacist involved in their care. Recruitment will take 
place only in the context of an established clinical care relationship. Eligible participants will have time to 
read the study description and consent paperwork as well as meet with a clinical research coordinator to have 
all questions answered. Any of the investigators can answer questions or review the document with the patient 
and their family as needed. Eligible patients giving informed consent to participate will be asked to sign the 
consent form before enrolling in the study. This consent will enable the investigators to review and store in a 


8 
V6_6/9/2023 
 
password protected database certain characteristics of the patient’s cancer history and response to 
chemotherapy including infusion hypersensitivity reactions of all grades (see section 5.2). Signed informed 
consent documents will be retained in study files and a copy will be uploaded to the patient’s electronic 
medical record (Epic or site-specific EMR system). 
 
4.2 Protection of patient rights and confidentiality 
 
4.2.1 Patients included in the study will be coded by random Subject Number (SN) which will be used in 
place of the patients’ medical record number (MRN). The key linking the patients’ MRN and SN 
will be stored in a secure, password-protected, HIPPA compliant system per institutional guidelines 
to which only the investigators and key personnel listed in the protocol have access. All clinical 
information and QoL survey data will be de-identified before data analysis is conducted. Study data 
will be entered into REDCap (Research Electronic Data Capture) at OSUWMC. Access to patient 
medical record number and other unique identifiers will be only given to approved research 
members. Participating co-sites will not be able to access other sites’ participant information; only 
information from their own site. 
 
4.2.2 All study files, paper or electronic, will be destroyed after 6 years from the final data collection date 
or by local institutional guideline, whichever is longest. 
 
4.3 Data collection 
 
Patients will have the following baseline and infusion data recorded for up to 12 doses of paclitaxel: 
• Demographics: such as age, gender, race, height, weight 
• Diagnosis of histologically confirmed breast cancer 
• ECOG performance status 
• chemotherapy regimen 
• dose and route of pre-medications given 
• dose and infusion rate of paclitaxel 
• dose number of paclitaxel 
• infusion hypersensitivity reaction (yes/no) 
• if applicable; time of hypersensitivity reaction relative to start of infusion 
• if applicable; symptoms, characteristics and course of the infusion hypersensitivity reaction 
including the use of oxygen and IV fluids 
• use of parenteral rescue medication (yes/no) 
• rescue medication(s) and doses administered 
• dose number of paclitaxel in which rescue medication was administered 
• whether or not the patient was re-challenged with paclitaxel successfully that day and if the infusion 
was completed 
• whether or not the patient had premedications resumed (where applicable) and was re-challenged in 
the future, and if they experience subsequent infusion HSR 
 
This study will utilize REDCap (Research Electronic Data Capture), a software toolset and workflow 
methodology for electronic collection and management of clinical and research data, to collect and store data. 
The Ohio State Research Information Technology Electronic Data Capture will be used as a central location 


9 
V6_6/9/2023 
 
for data processing and management. REDCap provides a secure, web-based application that provides an 
intuitive data manipulation interface, custom reporting capabilities, audit trail functionality, real-time data 
monitoring/querying of participant records, and variations of data exporting/importing. REDCap is hosted by 
OSUWMC IT in the Ackerman Datacenter (640 Ackerman Road; Room 345). 
 
REDCap instance is located on an internal OSUWMC network. Remote access to this network can be obtained 
over an encrypted VPN tunnel (AnyConnect). 
This VPN uses Protocol: DTLS and Cipher: 
RSA_AES_128_SHA1. Background checks are performed on all staff that are on the network or obtaining 
VPN access. The study REDCap database will be built and maintained with the assistance of the OSUCCC 
Recruitment, Intervention & Survey Shared Resource (RISSR). 
 
Due to the fact that data in this Section (4.3) are being shared between institutions, a data use agreement 
(DUA) will need to be put in place. Since Ohio State University will act as the coordinating center for this 
project, data from MNCCTN and OSU James Network sites will be sent to Ohio State University. Therefore, 
a data use agreement will be put into place between OSU and the respective institutions. 
 
4.4 Study Design 
This is a randomized, open-label, prospective trial. Up to 110 patients in this double arm study will be enrolled 
so that 100 can be randomized. Eligible patients initiating paclitaxel-based chemotherapy will be placed on 
study and observed for their first 2 doses of paclitaxel. Assuming that they did not experience a paclitaxel 
hypersensitivity reaction with the first 2 doses, they will be randomized at a 1:1 ratio to discontinue pre- 
medications for all subsequent treatments (experimental arm) or to continue pre-medications for all 
subsequent treatments (control arm). 
 
4.5 Endpoints 
 
Primary Endpoint: Determine the proportion of patients with grade 2 or greater infusion hypersensitivity 
reactions that require parenteral rescue medications to treat the reaction after the first 2 doses of paclitaxel 
with or without continued premedication dosing. 
 
Secondary endpoint: To determine whether an abbreviated pre-medication regimen results in improvement in 
patient-reported quality of life, as measured by an 11-point numerical analog scale. 
 
Exploratory Endpoints: 
• To evaluate the differences in a number of symptoms that might be improved, or worsened, by the 
hypersensitivity prevention drugs (see appendix II) 
• Report the number of patients who, after discontinuing pre-medications, request that the pre- 
medications be resumed to ameliorate side-effects that the patient thinks have worsened since pre- 
medications were stopped (i.e. nausea, rash, arthralgia). 
• Report weight changes across study periods for both arms of the study 
• Report the impact of patient self-reported allergies, prior to starting paclitaxel (2 or more versus 3 
or less), on the incidence of infusion HSR and rescue medication usage 
• To summarize patient outcomes by race. 
 
4.6 Stratification factors definition and justification 
1. Weekly paclitaxel (80 mg/m2) versus every 2-3-week paclitaxel (175 mg/m2) 
2. Planned regimen of HSR premeds: all IV vs all PO or mixed IV/PO 


10 
V6_6/9/2023 
 
5.0 Treatment Plan 
 
Study calendar 
Up to 14 
days prior 
to 
registration 
Paclitaxel 
#1 
Paclitaxel 
#2 
Time 
between 
dose 
2 and 3 
Paclitaxel 
#3 
Paclitaxel 
#4 
Paclitaxel 
#5 
Paclitaxel 
#6 
Paclitaxel 
#7 
Paclitaxel 
#8 
Paclitaxel 
#9 
Paclitaxel 
#10 
Paclitaxel 
#11 
Paclitaxel 
#12 
Tests & Observations 
Consent 
X 
Age, gender, race, Ht, Wt, ECOG 
X 
weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Diagnosis of histologically 
confirmed breast cancer 
X 
Serum or urine HCG test if clinical 
suspicion of pregnancy 
X 
Planned paclitaxel chemotherapy 
regimen 
X 
QOL survey prior to each dose of 
paclitaxel 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 1:1 
X 
Premedication regimen - drugs, 
doses, routes 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Paclitaxel dose (mg/m2, and total 
mg), infusion rate (mL/hr) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion HSR (yes/no) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Time of infusion HSR relative to 
start of paclitaxel infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Use of parenteral rescue 
medication (yes/no) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Drugs and doses of parenteral 
medication used 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Symptoms, characteristics, and 
course of the infusion HSR 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
If infusion HSR, was patient re- 
challenged with paclitaxel that 
day (yes/no) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
If infusion HSR, and patient was 
re-challenged with paclitaxel that 
day, was infusion completed 
(yes/no) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
If previous infusion HSR with dose 
#3 or beyond and premedications 
resumed, was paclitaxel re- 
challenged, and did they 
experience subsequent infusion 
HSR (yes/no) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
QOL - DAILY x 6 days after each 
dose of paclitaxel 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


11 
V6_6/9/2023 
 
5.1 Premedication treatment plan 
 
5.1.1 Patients will consent to study participation at any time from 14 days prior up to the day of initiating 
paclitaxel. Consenting patients prior to starting paclitaxel may result in some patients having to 
come off of the trial before randomization and subsequent planned study intervention, since the 
majority of infusion HSR’s are with the 1st or 2nd paclitaxel exposure. This has been accounted for in 
the sample size. 
 
5.1.2 All patients will receive dexamethasone 10-20 mg IV/PO, either diphenhydramine 25-50 mg IV/PO 
or cetirizine 10 mg IV/PO, and either famotidine 20 mg IV/PO, ranitidine 50 mg IV or 150 mg PO, 
or cimetidine 300 mg IV/PO, all given 30-45 minutes (no sooner than 30 minutes) prior to the start 
of paclitaxel and for the first 2 doses of paclitaxel. The paclitaxel premedication regimen employed 
at each participating site (i.e. dosages and routes of administration) will be per standard local 
practice. Prior to randomization changes to each patient’s premedication regimen including the dose 
or route of administration are discouraged, but allowed per the discretion of the ordering physician, 
if the patient experienced significant side effects to the aforementioned premedications after their 
first dose. 
 
5.1.3 Patients will have vital signs obtained prior to the start of each paclitaxel infusion. The 
chemotherapy nurse will remain bedside or in close proximity to the patient (provided the patient has 
a mechanism to call for the nurse) for a minimum of the first 15 minutes of each paclitaxel infusion 
regardless if the patient received premedication or not. 
 
5.1.4 Patients who experience an infusion hypersensitivity reaction (any grade) with the first or second 
dose of paclitaxel (regardless if rescue medications were administered) will not be eligible for 
randomization. These patients will not be included when calculating the primary endpoint. These 
patients will come off study at this time and have no further data collected. Patients who have not 
experienced an infusion hypersensitivity reaction with the first or second dose of paclitaxel, will be 
randomized at this time (prior to the 3rd dose) to the experimental arm (all premedications 
discontinued for future doses) or the standard of care arm (premedications continued for all future 
paclitaxel doses). 
 
5.1.5 Patients who have received their first 2 doses of paclitaxel without any evidence of infusion HSR 
and who were randomized to the experimental arm will have all pre-medications - including the 
steroid (dexamethasone), the H1 antagonist (diphenhydramine or cetirizine) and the H2 antagonist 
(famotidine/ranitidine/cimetidine) - discontinued prior to all future doses of paclitaxel. These pre- 
medications would not be resumed prior to any future paclitaxel doses, unless the patient did develop 
an infusion HSR from paclitaxel, at which point the patient would have reached the primary 
endpoint. 


12 
V6_6/9/2023 
 
5.1.6 A minority of patients may choose, or their oncology provider may feel it is clinically necessary, to 
restart premedications even if they have not experienced an infusion HSR; if this occurs, patients 
will be considered a protocol discrepancy and not included in the primary analysis. These patients 
will remain on study and continue with data collection, including QOL, for up to 12 doses of 
paclitaxel. A sensitivity analysis will be conducted that does include these patients. The number of 
patients who do decide to restart premeds will be collected, and the reason why they wished to 
resume. Replacement patients will not be added to the study to account for this scenario. 
 
5.1.7 For patients who are randomized to the standard of care arm, they will continue to receive 
premedications (dexamethasone, diphenhydramine/cetirizine, famotidine/ranitidine/cimetidine) to 
try to prevent hypersensitivity reactions prior to all future doses of paclitaxel. In the event the 
patient is reporting poor tolerability from the dexamethasone or diphenhydramine, and had NOT 
experienced a paclitaxel infusion hypersensitivity reaction with prior doses of paclitaxel, at the 
discretion of the local investigator, the dose and/or route of the dexamethasone may be decreased to 
as low as 6 mg, and the dose and/or route of the diphenhydramine may be decreased to as low as 
12.5 mg, but not discontinued. No dose adjustments are permitted for cetirizine or 
famotidine/ranitidine/cimetidine although the route may be changed. If the patient demanded to have 
premedications discontinued, or if the oncology provider felt it was clinically necessary, these 
patients would be considered a protocol discrepancy and not included in the primary analysis. These 
patients will remain on study and continue with data collection, including QOL, for up to 12 doses of 
paclitaxel. A sensitivity analysis will be conducted that does include these patients. Replacement 
patients will not be added to the study to account for this scenario. 
 
5.1.8 If receiving paclitaxel in combination with other chemotherapy, the paclitaxel will be infused first. 
 
5.1.9 The premedication, rescue medication and chemotherapy drugs involved in this protocol are all 
commercially available and will be billed to appropriate private insurance or government payers. 
 
5.1.10 Patients receiving subsequent doses of paclitaxel after premedications were discontinued who 
experience a hypersensitivity reaction and require rescue medication administration may have 
premedications resumed and managed at the discretion of the prescribing physician. These patients 
will be included when calculating the primary endpoint. 
 
5.1.11 For purposes of the study, all patients will be monitored for hypersensitivity/rescue medication usage 
and QOL and data recorded for up to 12 doses of paclitaxel (i.e. up to 10 doses after randomization), 
after which time the patient will come off study as the incidence of hypersensitivity reactions beyond 
this point would be increasingly rare. 


13 
V6_6/9/2023 
 
5.2 Rescue medication treatment plan 
 
5.2.1 The use of rescue medication will be defined as the administration of at least 1 parenteral rescue 
medication including hydrocortisone/methylprednisolone, diphenhydramine, famotidine (or other H2 
antagonist) or epinephrine. 
 
5.2.2 If the patient calls, or the nurse administering the paclitaxel observes the patient experiencing 
symptomatic chest tightness, flushing, abdominal pain, back pain, dyspnea, bronchospasm, 
hypotension/hypertension, angioedema or any other sign or symptom indicating need for parenteral 
rescue medication, the paclitaxel infusion will be stopped, and parenteral rescue medications 
administered and documented in accordance with local institutional policy. The local investigator 
may follow standard local practice for the treatment of the infusion hypersensitivity reaction in terms 
of alerts, actions, dosing, and order of rescue medication administration. 
 
5.2.2.1 Provided as a reference is Table 2 “Hypersensitivity Management” based on CTCAE v5.0 
or refer to sections 5.2.2.2 through 5.2.2.6 below for a suggested outline of infusion HSR 
management. 
 
5.2.2.2 If patient displays signs and symptoms of a grade 2 or higher paclitaxel infusion 
hypersensitivity reaction (requires treatment with parenteral medication), RN to administer 
hydrocortisone 100 mg IV push over 30 seconds or methylprednisolone 40 mg IV push 
over 3 minutes. Vital signs as clinically indicated to assess improvement or worsening of 
the reaction. 
 
5.2.2.3 If symptoms don’t begin to diminish, administer diphenhydramine 50mg IV push over 30 
seconds. Additionally, famotidine 20 mg (or other H2 antagonist) may be administered as 
well. 
 
5.2.2.4 If at any time the patient exhibits severe signs of bronchospasm, angioedema, or airway 
compromise, administer epinephrine 0.3 mg IM or SQ (0.3 mL of 1:1000 solution), 
epinephrine may be repeated as needed x 2 for a total dose up to 1 mg. 
 
5.2.2.5 Call the prescribing physician and discuss further management of the reaction, including 
fluids or oxygen. When signs of hypersensitivity reaction resolve to grade 1 or less, discuss 
re-initiation of the infusion 50% slower than previous rate. 
 
5.2.2.6 Paclitaxel order sets in the electronic medical record should contain standard parenteral 
medication orders for the treatment of infusion hypersensitivity reactions as outlined above. 
 
5.2.2.7 The nurse administering the paclitaxel will document the occurrence of any grade 
hypersensitivity reaction. 


14 
V6_6/9/2023 
 
6 Statistical Considerations 
 
6.1 Sample size justifications 
 
The true incidence of rescue medication after the 2nd dose is unknown; however, we expect the incidence to 
be less than 10%, which is the estimated incidence with doses one and two. A 0% to 5% incidence of rescue 
medication during doses 3 to 10 would be acceptable in patients who have had their premedications 
discontinued after the second dose. 
 
The primary aim of this randomized prospective trial is to estimate the difference in the rate of grade 2 or 
greater infusion HSR requiring parenteral treatment (rescue medication) in patients whose premedications are 
stopped after 2 doses of paclitaxel (experimental arm) to those continue to receive premedications (SoC arm). 
Patients will be randomized at the 1:1 ratio either to discontinue pre-medications for all subsequent treatments 
(experimental arm) or to continue pre-medications for all subsequent treatments (standard of care arm). A 
sample size of 90 patients (45 per arm), based on accrual feasibility, will provide sufficient precision for 
estimating the difference in grade 2 or higher HSR requiring parenteral treatment between the 2 arms. Table 
1 provides the potential confidence interval for various scenarios. 
 
 
Table 1. 95% Confidence Interval for the Difference in Grade 2+ HSR between Arms with 45 Evaluable 
Patients per arm 
Grade 2+ HSR requiring rescue medication 
Confidence Interval 
Discontinue Pre-meds 
Continue Pre-meds 
Observed difference 
Lower and Upper 
Limits 
Half Width 
.01 
.01 
0 
(-.04, .04) 
.04 
.04 
.01 
.03 
(-.03, .09) 
.06 
.04 
.04 
0 
(-.08, .08) 
.08 
.07 
.04 
.03 
(-.06, .12) 
.09 
 
This sample size is inflated to a total of 100 randomized patients (50 per arm) to account for 10% dropout due 
to cancellation, ineligibility, and protocol discrepancies post randomization. As we expect 10% of patients 
will experience infusion HSR in the first 2 cycles of paclitaxel, we anticipate enrolling 110 patients to have 
100 patients randomized. The sample size estimate was performed using a normal approximation of the 
binomial distribution and was calculated using PASS20. 
 
Update: as of May 2023, this trial has consented 75 patients, but we have had 18 consented patients who had 
an infusion HSR to the 1st or 2nd dose, and therefore they did not make it to randomization (24%).  This was 
higher than the 10% drop-out rate we had initially predicted who not make it to randomization.  In order to 
accommodate the original statistical plan to have 100 randomized (evaluable) patients, our plan is to increase 
accrual from 110 to 130 patients. Of these 130 patients, we expect about 76% (about 100) to be randomized. 
 
 
6.2 Accrual time 
 
Within our institution, approximately 3-5 eligible patients would enroll each month. As of May 2023, we have 
consented 75 patients. With our increased sample size (see section 6.1) and with  patients being treated on 


15 
V6_6/9/2023 
 
protocol and followed for up to 12 doses, we anticipate accrual can be completed in about 36-40 months. 
Efforts will be made to enroll 20% (20) minority patients to this trial. 


16 
V6_6/9/2023 
 
6.3 Analysis plan 
 
6.3.1 Primary endpoint: The primary analysis will follow the intention-to-treat principle where all patients 
randomized who were not a cancellation, not ineligible, did not decide to discontinue participation in 
the trial, or not a major deviation will be analyzed based on the arm to which they were randomized. 
The proportion of patients having infusion HSR of grade 2 or greater requiring parental treatment 
(rescue medications) will be estimated along with a 95% confidence interval. The difference in 
proportions of patients with grade 2 or greater infusion HSR needing rescue medication will be 
estimated along with a 95% confidence interval using the Z-test of normal approximations of the 
binomial distributions. As a sensitivity analysis, we will repeat the analysis including patients assigned 
to the discontinuation arm but decided to restart pre-medications and patients assigned to the 
continuation arm but demanded to have premedications discontinued as having experienced HSR. 
 
6.3.2 Secondary endpoint: Patient-reported quality of life, based on a single item 11-point numerical 
analog scale at each time point as well as change from baseline will be summarized by median (range) 
separately by treatment arm. Median (mean) QoL scores will be plotted longitudinally by treatment 
arm. QoL change from baseline will be compared between arms using the Wilcoxon rank-sum test. 
Data will be captured prior to each dose of paclitaxel and then every day for 6 days after each dose of 
paclitaxel (total of 7 days of QOL with each dose of chemotherapy). 
 
6.3.3 Exploratory endpoints: 
• Each symptom (listed appendix II) will be summarized by median (range) at each time point by 
treatment arm and the weekly average will be compared between arms using the Wilcoxon rank- 
sum test. 
• The frequency and percentages of patients who, after discontinuing pre-medications, request that 
the pre-medications be resumed to ameliorate side-effects that the patient thinks have worsened 
since pre-medications were stopped (i.e. nausea, rash, arthralgia) will be summarized. 
• Weight changes over time will be summarized at each time point using mean (standard deviation) 
and plotted by treatment arm. Weight change from baseline to 10 weeks post-randomization will 
be compared between arms that receive weekly paclitaxel. using a t-test of two independent 
samples. 
• Frequency of patient self-reported allergies (2 or more versus less) on the incidence of infusion 
HSR and rescue medication usage will be tabulated. 
• The rates of rescue medication by arms will be estimated by race/ethnicity group to explore 
whether there is a differential effect from stopping hypersensitivity reaction by race/ethnicity. 
 
6.3.4 Plan for missing data: 
We don’t anticipate missing data for the primary endpoint as patients will be required to come to the 
clinic for their paclitaxel treatment and rescue medication for infusion HSR of grade 2 or greater will 
be identified during paclitaxel treatment. In the rare event that patients, who have not experienced 
infusion HSR of grade 2 or greater requiring rescue medication, are lost to follow-up prior to 
completing their paclitaxel treatment, the reason for their discontinuation will be used to determine 
whether they should be included in the analysis of the primary endpoint. For all endpoints, the 
proportion of missing data will be summarized and if the missing data rate is higher than 10%, the 
mechanism of missing data will be evaluated. If the data appear to be missing at random, mixed model 
or equivalent likelihood methods will be used to compare the outcomes between treatment arms. If the 
missing data appear to be missing not at random, multiple imputation along with pattern mixture 
models will be used to compare outcomes between the treatment arms. 


17 
V6_6/9/2023 
 
7.0 Measurement / Instrumentation 
7.1 Hypersensitivity assessment: Following randomization, patients will be followed for up to 10 doses 
of paclitaxel. Since the clinical signs and symptoms of paclitaxel infusion HSR may vary and are 
partially influenced by provider/evaluator assessment, the nurse managing the patient should have 
standing orders to administer rescue medications as clinically indicated for a grade 2 or greater 
infusion HSR. For any patient who experiences an infusion hypersensitivity reaction, the local 
investigator may follow standard local practice for the treatment of the reaction – including stopping 
the infusion and administering rescue medications for those with grade 2 or greater infusion HSR 
(e.g., hydrocortisone/methylprednisolone, diphenhydramine, epinephrine, 0.9% NaCl fluids, 
oxygen). See table 2 below for suggested guidelines for the management of hypersensitivity reaction 
during paclitaxel infusion: 
 
 
Table 2: Hypersensitivity Management 
Mild symptoms (Grade 1) 
Moderate symptoms (Grade 2) 
Severe symptoms (> Grade 2) 
Mild/transient reaction with no 
intervention: e.g., transient 
flushing, sweating, mild rash. 
May or may not interrupt 
infusion; observe patient until 
symptoms have resolved; usually 
no medical intervention required, 
resume and complete paclitaxel 
infusion. 
Infusion interruption indicated 
but responds promptly to 
symptomatic treatment: e.g., 
rash, flushing, urticarial, 
shortness of breath, back, chest, 
or abdominal discomfort, 
anxiety, tachycardia. Administer 
hydrocortisone 100 mg IV, and 
diphenhydramine 50 mg IV if 
needed. Resume paclitaxel at a 
slower rate (25-50% of previous 
rate) after symptoms resolve to < 
grade 1. If reaction did not recur, 
may escalate to original rate. 
Stop and discontinue paclitaxel 
that day if symptoms recur after 
re-challenge. 
Not rapidly responsive to 
symptomatic medication and/or 
brief interruption of infusion, 
recurrence of symptoms 
following initial improvement or 
hospitalization required or life- 
threatening symptoms: e.g., 
sustained hypotension, 
angioedema, respiratory distress, 
anaphylaxis. If at any time 
patient experiences signs of 
angioedema or airway 
compromise, administer 
epinephrine 0.3 mg subcutaneous 
or intramuscular. Stop and 
permanently discontinue 
paclitaxel. 
 
Standard CTCAE criteria V5 Infusion related reaction will be utilized to characterize hypersensitivity 
reactions during paclitaxel infusions. The criteria for infusion-related reaction are listed in Appendix I 
and include mild/transient reaction with no intervention required (grade 1), therapy or infusion 
interruption indicated but responds promptly to symptomatic treatment (grade 2), not rapidly responsive 
to symptomatic medication and or brief interruption of infusion, recurrence of symptoms following 
initial improvement or hospitalization required (grade 3) and life threatening consequences requiring 
urgent intervention (grade 4). 


18 
V6_6/9/2023 
 
7.2 Overall quality of life (QOL) measurement and symptom experience evaluation: Steroids and H1 
antagonist pre-medication regimen can impact QOL in both positive and negative ways. For example, 
patients on steroids may experience increased positive energy or less pain or, alternatively, suffer from 
some or many of the negative effect of steroids, which might be cumulative. To better evaluate these 
effects on QOL, participants will be asked to rate their quality of life prior to each dose of paclitaxel 
and premedications and for 6 days following each dose of chemotherapy during the follow-up period 
on a single item numerical analog scale of 0-10. This scale will also be used to evaluate pain, insomnia 
symptoms and multiple other symptoms (see Appendix II). This is a validated simple measure to assess 
symptoms and quality of life in cancer patients and will serve as a secondary endpoint.19 QOL surveys 
will be administered electronically in REDCap or on paper, per participant preference. Data from paper 
surveys will be hand-entered into REDCap by approved research staff. 
8.0 Adverse Event Reporting 
 
8.1 Adverse events 
 
Potential risks and adverse events that may be reasonably anticipated (i.e., “expected”) should be described 
in the informed consent process/form and do not require prompt reporting to the IRB by Investigators and 
research staff. The following are examples of events that do not require prompt reporting: 
• Adverse events or injuries that are non-serious, expected, or unrelated; 
• Deaths not attributed to the research, e.g., from “natural causes,” accidents, or underlying disease 
and the Investigator has ruled out any connection between the study procedures and the participant’s 
death; 
• Protocol deviations or violations not involving risks to participants or unlikely to recur; 
• Complaints made by research participants not involving risks or complaints that were resolved; 
• interim analyses, or other reports, findings, or new information not altering the risk/benefit profile; 
• Problems or findings not involving risk (unless the Investigator or research staff member believes 
the information could affect participants’ willingness to continue in the research). 
 
Related internal and external events involving risk, but not meeting the prompt reporting requirements, 
should be reported in the Buck-IRB system, per OSU Office of Responsible Research Practices guidelines 
(https://orrp.osu.edu/irb/investigator-guidance/event/). 
 
8.2 Serious adverse events 
 
Reporting of adverse events will follow the OSU Human Research Protection Program Policy and Procedure 
for Event Reporting. The following events may represent unanticipated problems involving risks to subjects 
or others and would be promptly reported to the IRB of record: 
 
• Adverse events or injuries that are serious, unexpected, and related; 
• Protocol deviations or violations (or other accidental or unintentional changes to the protocol or 
procedures) involving risks or with the potential to recur; 
• Events requiring prompt reporting according to the protocol or sponsor; 
• Complaints made by research participants indicating unanticipated risks, or complaints that cannot 
be resolved by the research staff; 


19 
V6_6/9/2023 
 
• Unapproved changes made to the research to eliminate an apparent immediate hazard to a research 
participant 
• New information indicating an unexpected change in risks or potential benefits (e.g., 
literature/scientific reports or other published findings); 
• Other problem or finding (e.g., breach of confidentiality, loss of study data or forms, etc.) that an 
Investigator or research staff member believes could influence the safe conduct of the research. 
 
The events described above should be reported to the IRB of record using the sites approved event reporting 
mechanism, for example the OSU Buck-IRB system’s Event Report function within 10 days of the 
Investigator’s or research staff member’s learning of the event. Events resulting in temporary or permanent 
interruption of study activities by the Investigator or sponsor to avoid potential harm to participants should be 
reported immediately (within 48 hours) whenever possible. 


20 
V6_6/9/2023 
 
APPENDICES 
APPENDIX I – CTCAE v. 5 for infusion related reaction 
 
 
 


21 
V6_6/9/2023 
 
9.0 References 
 
1. 
Taxol injection piP, NJ: Bristol-Myers Squibb Company; July 2007. 
2. 
Obradovic MMS, Hamelin B, Manevski N, et al. Glucocorticoids promote breast cancer metastasis. 
Nature. Mar 2019;567(7749):540-544. 
3. 
v.1.2007 MD. 
4. 
Dieli-Conwright CM, Wong L, Waliany S, Bernstein L, Salehian B, Mortimer JE. An observational 
study to examine changes in metabolic syndrome components in patients with breast cancer receiving 
neoadjuvant or adjuvant chemotherapy. Cancer. Sep 1 2016;122(17):2646-2653. 
5. 
Guinan EM, Connolly EM, Healy LA, Carroll PA, Kennedy MJ, Hussey J. The development of the 
metabolic syndrome and insulin resistance after adjuvant treatment for breast cancer. Cancer nursing. 
Sep-Oct 2014;37(5):355-362. 
6. 
Lu LJ, Wang RJ, Ran L, et al. On the status and comparison of glucose intolerance in female breast 
cancer patients at initial diagnosis and during chemotherapy through an oral glucose tolerance test. PloS 
one. 2014;9(4):e93630. 
7. 
Chala E, Manes C, Iliades H, Skaragkas G, Mouratidou D, Kapantais E. Insulin resistance, growth 
factors and cytokine levels in overweight women with breast cancer before and after chemotherapy. 
Hormones (Athens). Apr-Jun 2006;5(2):137-146. 
8. 
Huang PL. A comprehensive definition for metabolic syndrome. Disease models & mechanisms. May- 
Jun 2009;2(5-6):231-237. 
9. 
Duggan C, Irwin ML, Xiao L, et al. Associations of insulin resistance and adiponectin with mortality in 
women with breast cancer. Journal of clinical oncology : official journal of the American Society of 
Clinical Oncology. Jan 1 2011;29(1):32-39. 
10. 
Camoriano JK, Loprinzi CL, Ingle JN, Therneau TM, Krook JE, Veeder MH. Weight change in women 
treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer. 
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Aug 
1990;8(8):1327-1334. 
11. 
Demark-Wahnefried W, Peterson BL, Winer EP, et al. Changes in weight, body composition, and 
factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant 
chemotherapy. Journal of clinical oncology : official journal of the American Society of Clinical 
Oncology. May 1 2001;19(9):2381-2389. 
12. 
Oyer DS, Shah A, Bettenhausen S. How to manage steroid diabetes in the patient with cancer. The 
journal of supportive oncology. Oct 2006;4(9):479-483. 
13. 
Alacacioglu A, Kebapcilar L, Gokgoz Z, et al. Leptin, insulin and body composition changes during 
adjuvant taxane based chemotherapy in patients with breast cancer, preliminary study. Indian journal of 
cancer. Jan-Mar 2016;53(1):39-42. 
14. 
Goodwin PJ, Ennis M, Pritchard KI, et al. Fasting insulin and outcome in early-stage breast cancer: 
results of a prospective cohort study. Journal of clinical oncology : official journal of the American 
Society of Clinical Oncology. Jan 1 2002;20(1):42-51. 
15. 
Berger MJ, Dunlea LJ, Rettig AE, Lustberg MB, Phillips GS, Shapiro CL. Feasibility of stopping 
paclitaxel premedication after two doses in patients not experiencing a previous infusion 
hypersensitivity reaction. Supportive care in cancer : official journal of the Multinational Association of 
Supportive Care in Cancer. Sep 2012;20(9):1991-1997. 
16. 
Berger MJ, Vargo C, Vincent M, et al. Stopping paclitaxel premedication after two doses in patients not 
experiencing a previous infusion hypersensitivity reaction. Supportive care in cancer : official journal of 
the Multinational Association of Supportive Care in Cancer. Jul 2015;23(7):2019-2024. 


22 
V6_6/9/2023 
 
17. 
Parinyanitikul N, Tanpipattanakul W, Poovorawan N, et al. Incidence of infusion hypersensitivity 
reaction after withholding dexamethasone premedication in early breast cancer patients not experiencing 
two previous cycles of infusion hypersensitivity reaction for weekly paclitaxel chemotherapy. 
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in 
Cancer. Jul 2018;26(7):2471-2477. 
18. 
de Castro Baccarin AL, Irene MN, de Iracema Gomes Cubero D, et al. The feasibility of dexamethasone 
omission in weekly paclitaxel treatment for breast cancer patients. Supportive care in cancer : official 
journal of the Multinational Association of Supportive Care in Cancer. Mar 2019;27(3):927-931. 
19. 
Singh JA, Satele D, Pattabasavaiah S, Buckner JC, Sloan JA. Normative data and clinically significant 
effect sizes for single-item numerical linear analogue self-assessment (LASA) scales. Health and quality 
of life outcomes. Dec 18 2014;12:187. 
20. 
Schneider et al. Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-E5103. JCO Precis Oncol. 
2017. 
21. 
Simon et al. The prevalence and pattern of chemotherapy-induced peripheral neuropathy among women 
with breast cancer receiving care in a large community oncology practice. Qual Life Res. 2017;26:2763- 
2772 
22. 
Sucheston et al. Genetic predictors of taxane-induced neurotoxicity in a SWOG phase III intergroup 
adjuvant breast cancer treatment trial (S0221). Breast Cancer Res Treat. 2011;130 :993-1002. 
23. 
Durham CG et al. Cetirizine versus diphenhydramine in the prevention of chemotherapy-related 
hypersensitivity reactions. J Oncol Pharm Pract. 2019 Sep;25(6):1396-1401. 
24. 
Holmes JP et al. Intravenous Cetirizine vs Intravenous Diphenhydramine for the Prevention of 
Hypersensitivity Infusion Reactions: Results of an Exploratory Phase 2 Study. J Infus Nurs. 2021 Nov- 
Dec;44(6):315-322. 

ICF_001.pdf: 
CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 1 of 11 
Form date: 
05/17/2019 
 
 
The Ohio State University Combined Consent to Participate in 
Research and HIPAA Research Authorization 
 
Study Title: 
Safely Stopping Premedications in Patients Receiving 
Paclitaxel: A Randomized Trial 
Principal Investigator: 
Michael Berger, Pharm D 
Sponsor: 
The Ohio State University 
 
• This is a consent form for research participation. It contains important information 
about this study and what to expect if you decide to participate. Please consider the 
information carefully. Feel free to discuss the study with your friends and family and 
to ask questions before making your decision whether or not to participate. 
• Your participation is voluntary. You may refuse to participate in this study. If you 
decide to take part in the study, you may leave the study at any time. No matter what 
decision you make, there will be no penalty to you and you will not lose any of your 
usual benefits. Your decision will not affect your future relationship with The Ohio 
State University. If you are a student or employee at Ohio State, your decision will 
not affect your grades or employment status. 
• You may or may not benefit as a result of participating in this study. Also, as 
explained below, your participation may result in unintended or harmful effects for 
you that may be minor or may be serious depending on the nature of the research. 
• You will be provided with any new information that develops during the study 
that may affect your decision whether or not to continue to participate. If you 
decide to participate, you will be asked to sign this form and will receive a copy of the 
form. You are being asked to consider participating in this study for the reasons 
explained below. 
 
Key Information About This Study 
The following is a short summary to help you decide whether or not to be a part of this study. 
More detailed information is listed later in this form. 
 
This study is for patients who are about to begin chemotherapy treatment with a drug called 
paclitaxel (Taxol™). Paclitaxel is commonly used in the treatment of solid tumors like breast 
cancer. This chemotherapy drug sometimes causes an allergic reaction when it is infusing into 
your vein. To prevent the reaction from happening or to reduce the severity of the reaction, 
patients are usually given what are called premedications. These premedications include 
steroids and antihistamine drugs. Repeated use of the premedications may cause side effects 
of their own, such as trouble sleeping, extra fluid staying in the body, weight gain, mood 
changes, lowered immune response, and stomach problems, to name a few. This study would 
like to gather data on patients who receive paclitaxel while discontinuing the use of 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 2 of 11 
Form date: 
05/17/2019 
 
 
premedication drugs. All patients will receive the first two doses of paclitaxel with the 
premedication drugs, since if there is a drug reaction to paclitaxel, it typically happens within 
the first two doses. Patients on this study will be randomly assigned to one of two groups: 
One group will receive the premedications with every paclitaxel dose during the course of 
treatment, and the other group will discontinue the premedication drugs after the first two 
doses of paclitaxel to monitor how they fare without premedications. Both groups will be 
monitored to see how often a reaction to the paclitaxel occurs. Both groups will also answer 
questions on surveys about their symptoms and quality of life immediately before each dose 
of paclitaxel and then for six days after each dose of paclitaxel during the study. 
 
1. Why is this study being done? 
 
As part of your cancer treatment, your doctor has ordered an intravenous (into your vein) 
chemotherapy drug called paclitaxel (Taxol™). There is a small chance that you may have 
an allergic reaction while the paclitaxel is being given. These reactions can range from 
mild (symptoms such as flushing, sweating, and itching) to severe (including shortness of 
breath, blood pressure changes and even death). The risk of having an allergic reaction is 
highest when you are receiving your first or second dose of paclitaxel. Your nurse will 
give you three different intravenous or oral medications (referred to as “premedications”): 
dexamethasone (Decadron™), diphenhydramine (Benadryl™) or cetirizine (Zyrtec™) and 
famotidine (Pepcid™) before your dose of paclitaxel is given in order to prevent an 
allergic reaction from happening. Despite receiving these premedications, you can still 
have an allergic reaction to paclitaxel. On days that you receive your paclitaxel treatment, 
a doctor will always be present in the building to help manage your treatment. Your nurse 
will monitor you closely while you are receiving paclitaxel. If you develop a serious 
allergic reaction while receiving paclitaxel, the nurse will stop the paclitaxel infusion and 
possibly give intravenous “rescue” medications, oxygen, or intravenous fluids to help treat 
the allergic reaction. The overwhelming majority of these allergic reactions will respond 
to this treatment. Symptoms of the allergic reaction often go away within 20-30 minutes, 
at which time the paclitaxel infusion can often be safely restarted. 
 
Normally, you would continue to receive all three premedications prior to every dose of 
paclitaxel, even if you have not had an allergic reaction with the first or second dose. 
These premedications can cause unwanted side effects, including abnormal blood sugars, 
fluid retention, insomnia, acne, muscle twitching and restlessness. Some of these 
unwanted side effects may worsen if you continue taking them for a long time. 
 
This study would like to monitor any effects and reactions for a group of patients who 
stop receiving premedications in order to prevent potential side effects from these drugs. 
All patients who agree to take part in this study will be monitored to make sure they have 
not had an allergic reaction with the first or second dose of paclitaxel. After that point, 
patients in the study will randomly be put into a group to either continue receiving 
premedications, or to stop receiving premedications. All patients will continue to be 
monitored and treated with rescue medications as needed. Your prescribed chemotherapy 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 3 of 11 
Form date: 
05/17/2019 
 
 
treatment does not change by taking part in this study. Your doctor may determine that it 
is best to restart premedications to avoid future allergic reactions. 
 
In order to monitor your symptoms and quality of life, a study coordinator will have all 
patients take a survey before each dose of paclitaxel, and then surveys will be provided to 
all participants for six days after each paclitaxel dose. This will help track symptoms and 
how you are feeling. 
 
2. How many people will take part in this study? 
 
Up to 130 people will take part in this study. 
 
3. What will happen if I take part in this study? 
 
By agreeing to take part in this study, you are agreeing to comply with the study 
requirements. You will receive a baseline survey to complete in REDCap or on paper. 
REDCap is a secure online data collection tool. 
 
You will receive dexamethasone, diphenhydramine or cetirizine and famotidine 
premedications followed by paclitaxel chemotherapy as ordered by your doctor. This is 
the current standard of care for all patients receiving paclitaxel. If you have not had an 
allergic reaction with your first or second dose of paclitaxel, you will be randomly placed 
into one of two study groups. The study staff will not put you into a group. This is done 
by a system that is used to randomly put people into groups. A member of the study team 
will let you know which group you are in. In one study group, premedications will be 
stopped. You will not receive these premedications prior to your future doses of 
paclitaxel. In the other study group, premedications will continue as standard of care. 
 
If you have an allergic reaction with your first or second dose of paclitaxel, no matter how 
mild the reaction is, your premedications will not be stopped; you will continue to receive 
them prior to all paclitaxel doses to prevent any further allergic reactions. 
 
Participants in this study will receive a REDCap survey by email or text message to fill 
out for 6 days after each paclitaxel dose. The surveys will take 5-7 minutes to complete 
and will ask about your symptoms and quality of life. Participants in both groups will 
answer the same surveys. If the electronic REDCap versions of the survey are not an 
option for you, 6 days’ worth of paper copies of the surveys will be provided to you at 
each chemotherapy visit to take home. Paper surveys will be completed at home each day 
then collected by the study coordinator at the next chemotherapy visit. 
 
By agreeing to take part in the study, you are agreeing to let the study team to access your 
medical records to collect information about you (race, ethnicity, height, and weight), 
your cancer history (age at diagnosis, stage) and cancer treatment history (types and doses 
of chemotherapy medications). The study team will also look at clinical information 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 4 of 11 
Form date: 
05/17/2019 
 
 
related to any allergic reactions and side effects, rescue treatments, and whether you 
receive premedications again. This information is used to describe who was in the study 
and to explain the clinical effects of your treatment. 
 
4. How long will I be in the study? 
 
You will be enrolled in this study while you receive up to 12 doses of paclitaxel. Your 
physician will decide how many doses and often you will receive your paclitaxel 
chemotherapy; this will determine how long you are in the study. This may range from 2 
months to 4 months. You will complete a survey prior to each of the doses of paclitaxel 
that you receive, and then you will be given a series of 6 daily surveys to complete 
starting the day after paclitaxel. Each survey will take approximately 5-7 minutes. In total, 
we expect for you to spend about 8-10 hours doing the surveys over the course of the 2-4 
months on study. 
 
5. Can I stop being in the study? 
 
You may leave the study at any time. If you decide to stop participating in the study, 
there will be no penalty to you, and you will not lose any benefits to which you are 
otherwise entitled. Your decision will not affect your future relationship with The Ohio 
State University. 
 
6. What risks, side effects or discomforts can I expect from being in the study? 
 
There are risks to taking part in any research study. 
 
The surveys ask about symptoms and quality of life associated with treatment. You may 
choose not to answer one or more of the questions. Your information and surveys are not 
monitored in real time. If you are having any urgent symptoms, you should seek medical 
attention. 
 
Loss of confidentiality is a risk; however, we have taken multiple precautions to limit this. 
Once enrolled, you will be given a unique study ID. This ID will be used in all of the 
databases. Some participants will use REDCap electronic data capture tool for the online 
surveys. REDCap provides a secure, web-based, HIPAA compliant application and 
password protected platform that is housed behind the medical center’s firewall. Other 
participants may choose to complete paper surveys that will be coded with only your 
study ID, entered into REDCap after they are returned to the study team, and then will be 
shredded. 
 
There may be other privacy risks that we have not foreseen. While we believe the risks to 
you are very low, we are unable to tell you exactly what all the risks are. During the 
research study, you will be provided with any new information that may affect your health 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 5 of 11 
Form date: 
05/17/2019 
 
 
or willingness to participate. You may be asked to sign a new consent form that shows 
that you have been informed of new information relating to this research study. 
 
The risk of having an allergic reaction is highest when you are receiving your first or 
second dose of paclitaxel, so when you begin taking part in this study, you will be 
receiving the standard premedications prior to your paclitaxel chemotherapy. You are at 
no greater risk of side effects or discomforts from these drugs or allergic reaction from 
paclitaxel than other patients who are not taking part in this study. If you do not have an 
allergic reaction, and your premedications are discontinued prior to your third dose of 
paclitaxel, you may have a slightly increased risk of having an allergic reaction to 
paclitaxel. Based on available evidence, your doctor believes this risk to be small. These 
paclitaxel reactions can range from mild (symptoms such as flushing, sweating, and 
itching) to severe (including shortness of breath, blood pressure changes and in rare cases, 
even death). Your doctor and nurse will continue to monitor your paclitaxel infusions very 
closely. If you develop a serious allergic reaction while receiving paclitaxel, the nurse will 
stop the paclitaxel infusion and possibly administer intravenous “rescue” medications, 
oxygen, or intravenous fluids to help treat the allergic reaction. Your doctor or another 
doctor is always present in the building to help manage your treatment. 
 
The effects of paclitaxel on an unborn baby may be harmful. Therefore, if you are 
pregnant, you cannot be in this study. If you are a woman of childbearing potential, you 
must not become pregnant while in this study. If you are capable of bearing children, you 
may be required to take a pregnancy test before entry into this study if your doctor 
suspects you may be pregnant. If you become pregnant during the study, you will be 
withdrawn from the study. If at any time during the study or for up to 120 days after you 
stop study treatment you suspect that you have become pregnant, please notify the study 
doctor immediately. The risk to pregnant partners or the baby of male patients receiving 
paclitaxel is not known. Female patients of reproductive potential as well as fertile male 
patients with partners who are female of reproductive potential must agree to abstain from 
sexual intercourse or to use a double barrier method (ie. condom, diaphragm, cervical cap 
with spermicidal foam, cream, or gel) from the time of giving informed consent through 
the duration of study treatment with paclitaxel (up to 12 weeks). You must not nurse 
(breastfeed) while on this study because paclitaxel may enter breast milk and possibly 
harm your child. 
 
7. What benefits can I expect from being in the study? 
 
There may not be a direct benefit to you as a result of your participation in this study. It is 
possible that information learned from you participation in this study will benefit patients 
receiving paclitaxel in the future. By enrolling in this study, it is possible that you will 
have your paclitaxel premedications (dexamethasone, diphenhydramine or cetirizine, and 
famotidine) stopped prior to your third dose of paclitaxel. Therefore, the unwanted side 
effects sometimes caused by these drugs could be avoided. 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 6 of 11 
Form date: 
05/17/2019 
 
 
8. What other choices do I have if I do not take part in the study? 
 
You may choose not to participate without penalty or loss of benefits to which you are 
otherwise entitled. 
 
9. What are the costs of taking part in this study? 
 
If you use a smartphone and choose to receive your surveys by text message, you may 
incur charges from the daily text messages, depending on your cell phone plan. Email 
delivery is an option for no cost. The research portion of this study involves withholding 
premedications and collecting data; you and/or your insurance company will not be 
charged for any other aspect of this research. All other charges regarding your cancer 
treatment are considered standard of care and will be billed to you and/or your insurance 
company. 
 
You or your insurance company will be charged for portions of your care during this 
research study that are considered standard care. Standard of care is the care that you 
would receive regardless of whether you were enrolled in the study or not. You may be 
responsible for co-payments, co-insurance, premiums, and deductibles that are typical for 
your insurance coverage. 
 
If you have questions about your insurance coverage, or the items you might be required 
to pay for, please call financial services for information at 800-293-5066. You may find 
additional information at the following website, https://cancer.osu.edu/for-patients-and- 
caregivers/patient-information/finance-and-insurance-information. 
 
The National Cancer Institute provides an online resource to help people participating in 
cancer clinical trials understand which services their insurance company is required by 
law to pay. This can be found at the website below or can be provided by the study team: 
www.cancer.gov or 1-800-4-CANCER (1-800-422-6237). 
 
10. Will I be paid for taking part in this study? 
 
You will not be paid to take part in this study. If you choose to take part in this study, it 
will be on a voluntary basis. 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 7 of 11 
Form date: 
05/17/2019 
 
 
11. What happens if I am injured because I took part in this study? 
 
If you suffer an injury from participating in this study, you should notify the researcher or 
study doctor immediately, who will determine if you should obtain medical treatment at 
The Ohio State University Wexner Medical Center. 
 
The cost for this treatment will be billed to you or your medical or hospital insurance. The 
Ohio State University has no funds set aside for the payment of health care expenses for 
this study. 
 
12. What are my rights if I take part in this study? 
 
If you choose to participate in the study, you may discontinue participation at any time 
without penalty or loss of benefits. By signing this form, you do not give up any personal 
legal rights you may have as a participant in this study. 
 
You will be provided with any new information that develops during the course of the 
research that may affect your decision whether or not to continue participation in the 
study. 
 
You may refuse to participate in this study without penalty or loss of benefits to which 
you are otherwise entitled. 
 
An Institutional Review Board responsible for human subjects research at The Ohio State 
University reviewed this research project and found it to be acceptable, according to 
applicable state and federal regulations and University policies designed to protect the 
rights and welfare of research participants. 
 
13. Will my de-identified information be used or shared for future research? 
 
No. 
 
14. Will my study-related information be kept confidential? 
 
We will work to make sure that no one sees your survey responses without approval. But, 
because REDCap uses the Internet, there is a chance that someone could access your 
online responses without permission. In some cases, this information could be used to 
identify you. Your data will be protected with a code to reduce the risk that other people 
can view the responses. 
 
Efforts will be made to keep your study-related information confidential. However, there 
may be circumstances where this information must be released. For example, personal 
information regarding your participation in this study may be disclosed if required by state 
law. 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 8 of 11 
Form date: 
05/17/2019 
 
 
Also, your records may be reviewed by the following groups (as applicable to the 
research): 
• 
Office for Human Research Protections or other federal, state, or international 
regulatory agencies; 
• 
U.S. Food and Drug Administration; 
• 
The Ohio State University Institutional Review Board or Office of Responsible 
Research Practices; 
• 
The sponsor supporting the study, their agents or study monitors; and 
• 
Your insurance company (if charges are billed to insurance). 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. law. This website will not include information that can identify you. At 
most, the website will include a summary of the results. You can search the website at 
any time. 
 
15. HIPAA AUTHORIZATION TO USE AND DISCLOSE INFORMATION FOR 
RESEARCH PURPOSES 
 
I. 
What information may be used and given to others? 
 
• Past and present medical records; 
• Research records; 
• Records about phone calls made as part of this research; 
• Records about your study visits; 
• Information that includes personal identifiers, such as your name, or a number 
associated with you as an individual; 
• Records about the medications you receive will be tracked 
 
II. 
Who may use and give out information about you? 
 
Researchers and study staff. 
 
III. 
Who might get this information? 
 
• The sponsor of this research. “Sponsor” means any persons or companies that are: 
• working for or with the sponsor; or 
• owned by the sponsor. 
• Authorized Ohio State University staff not involved in the study may be aware that 
you are participating in a research study and have access to your information; 
• If this study is related to your medical care, your study-related information may be 
placed in your permanent hospital, clinic, or physician’s office record; 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 9 of 11 
Form date: 
05/17/2019 
 
 
IV. 
Your information may be given to: 
 
• The U.S. Food and Drug Administration (FDA), Department of Health and Human 
Services (DHHS) agencies, and other federal and state entities; 
• Governmental agencies in other countries; 
• Governmental agencies to whom certain diseases (reportable diseases) must be 
reported; and 
• The Ohio State University units involved in managing and approving the research 
study including the Office of Research and the Office of Responsible Research 
Practices. 
 
V. 
Why will this information be used and/or given to others? 
 
• To do the research; 
• To study the results; and 
• To make sure that the research was done right. 
 
VI. 
When will my permission end? 
 
There is no date at which your permission ends. Your information will be used 
indefinitely. This is because the information used and created during the study may be 
analyzed for many years, and it is not possible to know when this will be complete. 
 
VII. May I withdraw or revoke (cancel) my permission? 
 
Yes. Your authorization will be good for the time period indicated above unless you 
change your mind and revoke it in writing. You may withdraw or take away your 
permission to use and disclose your health information at any time. You do this by 
sending written notice to the researchers. If you withdraw your permission, you will not 
be able to stay in this study. When you withdraw your permission, no new health 
information identifying you will be gathered after that date. Information that has already 
been gathered may still be used and given to others. 
 
VIII. What if I decide not to give permission to use and give out my health 
information? 
 
Then you will not be able to be in this research study and receive research-related 
treatment. However, if you are being treated as a patient here, you will still be able to 
receive care. 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 10 of 11 
Form date: 
05/17/2019 
 
 
IX. 
Is my health information protected after it has been given to others? 
 
There is a risk that your information will be given to others without your permission. Any 
information that is shared may no longer be protected by federal privacy rules. 
 
X. 
May I review or copy my information? 
 
Signing this authorization also means that you may not be able to see or copy your study- 
related information until the study is completed. 
 
16. Who can answer my questions about the study? 
 
For questions, concerns, or complaints about the study, or if you feel you have been 
harmed as a result of study participation, you may contact Michael Berger, Pharm D at 
614-293-0191 or Michael.Berger@osumc.edu. 
 
For questions related to your privacy rights under HIPAA or related to this research 
authorization, please contact Kathleen Ojala at 614-293-6482 or 
Kathleen.Ojala@osumc.edu. 
 
For questions about your rights as a participant in this study or to discuss other study- 
related concerns or complaints with someone who is not part of the research team, you 
may contact the Office of Responsible Research Practices at 1-800-678-6251. 
 
If you are injured as a result of participating in this study or for questions about a study- 
related injury, you may contact Michael Berger, Pharm D at 614-293-0191 or 
Michael.Berger@osumc.edu. 


CONSENT & 
AUTHORIZATION 
IRB Protocol Number: 
IRB Approval date: 
Version: 
2021C0059 
8/1/2023 
6/9/2023 
Page 11 of 11 
Form date: 
05/17/2019 
 
 
Signing the consent form 
 
I have read (or someone has read to me) this form and I am aware that I am being asked to 
participate in a research study. I have had the opportunity to ask questions and have had them 
answered to my satisfaction. I voluntarily agree to participate in this study. 
 
I am not giving up any legal rights by signing this form. I will be given a copy of this 
combined consent and HIPAA research authorization form. 
 
 
 
Printed name of participant 
Signature of participant 
 AM/PM 
Date and time 
Printed name of person authorized to consent for 
participant (when applicable) 
Signature of person authorized to consent for participant 
(when applicable) 
 
 
 AM/PM 
Relationship to the participant 
Date and time 
 
 
Investigator/Research Staff 
 
I have explained the research to the participant or his/her representative before requesting the 
signature(s) above. There are no blanks in this document. A copy of this form has been given 
to the participant or his/her representative. 
 
 
 
Printed name of person obtaining consent 
Signature of person obtaining consent 
 AM/PM 
Date and time 
 
Witness(es) - May be left blank if not required by the IRB 
 
 
 
Printed name of witness 
Signature of witness 
 AM/PM 
Date and time 
Printed name of witness 
Signature of witness 
 AM/PM 
Date and time