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Informed Consent Form for Clinical Trial

“The Efficacy and Safety of Eutideron, Etoposide, and Bevacizumab in Patients

with Brain Metastases from Breast Cancer”

Student’s Name:

School:

Course:

Professor’s Name:

Date:
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Tianjin Medical University Cancer Institute and Hospital, Research Consent Form

Protocol Title: “The Efficacy and Safety of Eutideron, Etoposide, and Bevacizumab
in Patients with Brain Metastases from Breast Cancer”
Principal Investigator: Yehui Shi, MD, PhD
Description of the Subject population: Females who are above eighteen
diagnosed with brain tumors from carcinoma of the breast.

About the research study:

We appreciate your interest in our clinical study. The study involves research aimed at
advancing medical knowledge and improving patient care.
A phase II research study for patients diagnosed with breast carcinoma patients with
brain tumors is being conducted. The investigation follows an allocation of subjects to a
single group, non-blind study. This includes a treatment plan of three medications
namely bevacizumab, etoposide, and eutideron.
The allocation of subjects to investigate comparator medications namely bevacizumab,
etoposide, and eutideron in one group. We are asking you to participate in this clinical
research for females diagnosed with brain tumors from breast carcinoma who are
eighteen to eighty years old encompassing both adults and geriatric patients.
Your decision to engage in this research study must be voluntary and there is no
obligation to participate in the research study. Moreover, if the research study has
appalling health repercussions, you have the right to withdraw from the research study.
The purposes of the research:
We are doing this clinical research to determine whether the proposed treatment plan of
bevacizumab, etoposide, and eutideron can benefit the research subjects suffering from
brain tumors from carcinoma of the breast. Additionally, we need to comprehend the
therapeutic index of the proposed treatment protocol of bevacizumab, etoposide, and
eutideron and do not have appalling health repercussions on subjects.
 The United States Food and Drug Administration (USFDA) status: Bevacizumab,
etoposide, and eutideron for the mitigation of brain tumors from carcinoma of the
breast is not yet approved by the U.S. Food and Drug Administration (FDA).
 Approximate ratio of subjects: About 43 subjects especially females who are
above eighteen diagnosed with brain tumors from carcinoma of the breast are
anticipated to participate in this research. We will enroll approximately forty-three
subjects at the Tianjin Medical University Cancer Institute and Hospital.
The study is being funded by Tianjin Medical University Cancer Institute and Hospital.
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Expected duration of the individual’s participation:

It will take approximately 36 months to accomplish the investigation. Throughout this
period, you will be requested to attend several study visits to Tianjin Medical University
Cancer Institute and Hospital.
The study commenced on July 20, 2022, with an anticipated primary completion date of
July 20, 2023, and an overall anticipated completion date of July 20, 2025.
The procedures to be followed:
A minimum of four to six sessions of the treatment course of bevacizumab, etoposide,
and eutideron should be administered as a part of the study protocol.
 Use of bevacizumab as ongoing treatment till the condition of subjects worsens
or severe adverse reactions.
 Brain magnetic resonance imaging (MRI) is performed at the initiation of the
investigation and subsequently every six weeks after being enrolled.
 Subjects who exhibit positive responses should be visited at intervals of nine
weeks at Tianjin Medical University Cancer Institute and Hospital.
 The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) is
utilized to examine the extent of central nervous system tumors.
 Response Evaluation Criteria in Solid Tumors (RECIST) is utilized to examine
non-central nervous system tumors.
Communication and periodic follow-up: If the condition gets worse, kindly contact Yehui
Shi, MD, Ph.D. at the number listed below on this consent form.
Identification of any experimental procedures:
You are invited to participate in a clinical trial investigating the safety and efficacy of a
novel treatment regimen for breast cancer patients with brain metastases. The
experimental treatment consists of a combination of three drugs – Eutideron, Etoposide,
and Bevacizumab. This regimen is not yet established in standard medical practice, and
its safety and effectiveness are currently under investigation. The primary goal of the
study is to evaluate whether this combination can enhance disease control, prolong
survival, or yield other positive clinical outcomes.
Moreover, Potential risks include side effects associated with the drugs, while benefits
may encompass disease response or improved quality of life. Standard treatment
alternatives for brain metastases in breast cancer patients are available and will be
discussed with you. Participation is voluntary, and declining will not impact your
standard care.
Foreseeable risks or discomforts to the participant:
 Drug-Related Risks: The medications Eutideron, Etoposide, and Bevacizumab,
integral to the experimental treatment, carry potent effects. Common side effects
encompass nausea, fatigue, hair loss, and changes in blood cell counts, while
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less frequent but serious risks include allergic reactions, bleeding, and infection.
Bevacizumab may heighten the risk of high blood pressure, proteinuria, and
gastrointestinal perforation.
 Brain Metastases-Specific Risks: Brain metastases inherently pose risks,
including seizures, neurological deficits, and increased intracranial pressure. The
treatment may contribute to temporary or permanent worsening of neurological
symptoms, and there's a risk of disease progression despite intervention.
 General Discomforts: Patients may experience general discomfort with frequent
clinic visits for drug administration and monitoring. Blood draws and imaging
scans, while necessary, may cause mild discomfort.
 Unknown Risks: Given the investigational nature of the treatment, unforeseen
risks may emerge during the trial. Patient safety is a priority, and the study team
will closely monitor participants throughout the trial. Any concerns should be
openly discussed with the study staff to facilitate informed decision-making.
Expected benefits from the research:
 Advancing Medical Knowledge: Participation in the clinical trial allows you to
contribute to a deeper understanding of your disease or condition, actively
contributing to advancements in treatments and preventive strategies. Your
involvement not only benefits you but also provides valuable insights for others
facing similar health challenges, contributing to the broader scientific knowledge.
 Active Role in Your Health: Engaging in clinical research empowers you to take
a more active role in managing your health, making you an integral part of the
scientific process and contributing to meaningful discoveries. Through this
involvement, you play a crucial role in shaping the future of medical treatments
and strategies.
By participating, you may also gain increased awareness about your disease or
condition, with access to information about support groups and resources that can
enhance your overall well-being. Additionally, some participants join clinical trials with
the hope of accessing new treatments before they become widely available, providing
an opportunity for early intervention with novel approaches that may not yet be
accessible outside the study. It's important to note that participation is entirely voluntary,
and your safety remains a top priority throughout the research process.
Alternative procedures or courses of treatment for participants:
While this clinical trial investigates a novel treatment for breast cancer patients with
brain metastases, it's crucial to note the existence of established standard treatment
options beyond this study. These may encompass surgery, radiation therapy,
chemotherapy, or targeted therapies, and discussing these alternatives with your
healthcare provider is essential for informed decision-making. Recognizing the
uniqueness of each patient's situation, treatment decisions should consider factors such
as overall health, tumor characteristics, and personal preferences, with the healthcare
team tailoring recommendations to individual needs.
Importantly, participation in this trial doesn't preclude exploring other clinical trials or
investigational treatments. If eligible for additional trials, the study team can guide
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relevant options. Encouraging open discussions about treatment choices, the study
emphasizes your right to seek second opinions and explore all available avenues.
Confidentiality of Participant Records:
We respect your privacy. Any information collected during this clinical trial will be kept
strictly confidential. Your identity will be protected, and your records will be identified by
a unique study ID rather than your name or personal details. Only authorized personnel
involved in the research will have access to the confidential information. We assure you
that we will not disclose any personal details without obtaining your explicit consent
(written or verbal), except as required by law or regulatory authorities.
Compensation and Medical Treatments:
 Compensation: As a study participant, you shall receive no direct financial
compensation for your involvement in this clinical study.
 Medical Treatments: In the very least likely for the event of an injury related to
the study to happen however in any adverse event medical treatments will be
provided at no cost to you. These treatments may include standard medical care
or investigational therapies. If you experience any adverse effects, we will
promptly address the issue and provide appropriate attention medical and
otherwise.
For further information about available treatments or compensation, please contact our
study coordinator (details provided below).
Contact Information:
Questions About the Research: If you have any questions about the study, your rights
as a participant, or the processes involved, please do not hesitate to contact the
research team. We are here to address your concerns and provide clarifications.
 Name: Yehui Shi, MD,Phd
 Phone Number:18622221183
 Email: shiyehui@tjmuch.com
Research-Related Injury: In the event of a research-related injury, please contact the
study coordinator immediately. Our team will guide you through the mandatory steps
and ensure your well-being.
Voluntary Participation and Right to Withdraw
 Voluntary Participation: We confirm that your participation in this trial is entirely
voluntary. You have the right to decline participation without any negative
consequences at any point. Also, please note that the refusal to participate shall
not affect any benefits or entitlements you may otherwise receive.
 Withdrawal: You may choose to discontinue your participation at any time
without penalty. If you decide to discontinue, it will not impact your medical care
or other rights.
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Description of Clinical Trial and Confidentiality

This clinical investigation will be available on www.ClinicalTrials.gov with a description,
and results database of publicly and privately funded human clinical trials worldwide
(ClinicalTrials.gov.,2023). Your study data will remain secret to the degree allowed by
law. This site will not include your personal information. At most, it will summarize the
findings authorized by Tianjin Medical University Cancer Institute and Hospital, or
regulatory agency officials may audit your medical records.

Understanding Potential Risks:

It's important to recognize that participating in this clinical trial may expose you to
certain risks that we cannot predict with certainty at this time. The study may involve
risks to the individual participant. If you are or may become pregnant, it's crucial to
understand that there may be risks to the developing embryo or fetus (Saini et al.,
2020). It's important to discuss any concerns or questions you have about pregnancy
and participation in the trial with your healthcare provider and the research team.
However, it's essential to recognize that despite our best efforts, there may still be
unknown risks associated with participation in this study.

Anticipated Circumstances for Termination

 Protocol Deviations: Failure to follow medication regimens, missing study visits,

or insufficient data collection may lead the investigator to discontinue a
participant's participation. The study results' integrity and validity depend on
procedure compliance.
 Medical or Ethical Concerns: The investigator can terminate a participant's
participation in the study if new medical information or ethical concerns warrant it.
 Participant Withdrawal of Consent: Participants may resign from the research
at any time; however, the investigator may discontinue their participation if they
decide it is no longer in their best interest.
.
Additional costs for participation:

Participation in this research may involve certain additional costs to you. These costs
could include, but are not limited to travel expenses, parking fees, etc. It is important to
note that for any potential financial responsibilities, e.g., insurance co-payments,
medication costs, etc, we are committed to providing as much support as possible to
minimize any financial burden associated with your participation. Before deciding to
participate, we encourage you to carefully consider these potential costs and discuss
any concerns or questions with the research team. Your well-being and understanding
of the financial aspects of participation are important to us. Hence company is offering
compensation for participants to help cover any additional costs associated with
participating in the research. In this case, where the company will pay $50 for every
visit.

Stopping Early and Protocols for Systematic Conclusion of Participation:

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Sometimes, studies may need to be stopped early for various reasons, such as new
safety concerns, lack of efficacy, or changes in the study design. If the study is stopped
early, participants will be informed of this decision. In the event of an early study
termination, participants may be asked to come in for a final visit to assess their health
and well-being, and researchers will provide relevant information regarding the
termination.
As a participant in this research, possess the right to withdraw voluntarily at any point
without encountering any adverse consequences. The informed consent form explicitly
articulates that your decision to withdraw from the study will have no impact on your
medical care or your relationship with your healthcare provider. You need to
comprehend that you have the freedom to withdraw without the obligation to provide a
reason, and your choice to discontinue participation will be honored and respected by
the research team.
If a participant decides to withdraw from the research, the following procedures will be
followed:
 Notification: Participants are strongly encouraged to promptly notify the
research team if they choose to withdraw from the study. The contact information
for study personnel is available in the informed consent form for ease of
communication.
 Exit Interview (Optional): Participants may be offered the opportunity to engage
in an optional exit interview. This allows participants to provide feedback on their
study experience, aiding researchers in enhancing the design and execution of
future studies. Participation in the exit interview is entirely voluntary.
 Remaining Data: With the participant's explicit consent, any data collected up to
the point of withdrawal may be considered for inclusion in the study analysis.
Alternatively, participants can request the exclusion of their data from the
analysis.
 Follow-Up Care: Participants will be informed about any necessary follow-up
care or procedures after their withdrawal from the study. This may involve
transitioning back to standard medical care, and all details will be communicated.
 Compensation: Participants will be entitled to compensation for completed study
visits, even if they choose to withdraw. The compensation details are outlined in
the informed consent form, and participants are encouraged to review this
information thoroughly.

New developments during the research impacting individual's participation

decisions:

Throughout this research study, if significant new findings emerge that may impact your
decision to continue participating, we are committed to providing you with timely and
relevant information. You will be promptly informed of any important developments that
may influence your willingness to continue your involvement in the study. This ensures
that you are kept informed about the research process and can make decisions about
your participation based on the most up-to-date information available. We encourage
open communication and are here to address any questions or concerns you may have
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regarding these findings. Your well-being and informed decision-making are of utmost
importance to us.

The number of individuals involved:

The study aims to enroll approximately 2000 participants. Please note that this is an
estimate, and the actual number may vary based on factors such as recruitment
success and other logistical considerations. Your participation is valuable and
contributes to the overall success of the research.

For inquiries?
If you have inquiries regarding your participation in this study or experience a research-
related injury, you may consult with either your study doctor or the designated physician
overseeing the study at this institution. That person is:

John Snow, MD, PhD 222-222-4478

_______________________ _________________________
Name Telephone

This study has been reviewed and approved by the Tianjin Medical University Cancer
Institute and Hospital ID # NCT05781633. If you have any ethical concerns about the
study or the way it is conducted,
please contact Yehui Shi, MD, Ph.D. Phone:18622221183
Email: shiyehui@tjmuch.com

SIGNATURES
 Every query I had has been addressed.
 I understand the details provided in this informed consent document.
 I authorize the retrieval of my medical records and specimens, per the terms outlined
in this consent form.
 Signing this consent form does not result in a forfeiture of any of my legal rights.
 I am aware that my family doctor or healthcare provider may be informed about my
involvement in this study.
 I consent or consent on behalf of the individual I am responsible for to participate in
this study.

____________________________ ________________ __________________

Signature of Participant NAME Date
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____________________________ __________________ ___________________

Signature of Person In-charge PRINTED NAME & ROLE Date
References

ClinicalTrials.gov. (2023). The Efficacy and Safety of Eutideron, Etoposide, and

Bevacizumab in Patients With Brain Metastases From Breast Cancer.

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Saini, A., Kumar, M., Bhatt, S., Saini, V., & Malik, A. (2020). CANCER CAUSES AND

TREATMENTS. INTERNATIONAL JOURNAL of PHARMACEUTICAL

SCIENCES and RESEARCH, 11(7). https://doi.org/10.13040/ijpsr.0975-

8232.11(7).3121-34

Chen, T. W.-W., Dai, M.-S., Tseng, L.-M., Chen, S.-C., Chao, T.-Y., Chao, T.-C.,

Chang, Y.-C., Chiu, C.-F., Liu, C.-T., Lin, C.-H., Liu, C.-Y., Chen, Y.-F., Chang,

D.-Y., Yu, J.-C., Rau, K.-M., Hsieh, Y.-Y., Shen, S.-C., Huang, S.-M., Cheng, A.-

L., & Lu, Y.-S. (2023). Whole-Brain Radiotherapy Alone vs Preceded by

Bevacizumab, Etoposide, and Cisplatin for Untreated Brain Metastases From

Breast Cancer: A Randomized Clinical Trial. JAMA Oncology, e235456.

https://doi.org/10.1001/jamaoncol.2023.5456

Leone, J. P., Emblem, K. E., Weitz, M., Gelman, R. S., Schneider, B. P., Freedman, R.

A., Younger, J., Pinho, M. C., Sorensen, A. G., Gerstner, E. R., Harris, G., Krop,

I. E., Morganstern, D., Sohl, J., Hu, J., Kasparian, E., Winer, E. P., & Lin, N. U.

(2020). Phase II trial of carboplatin and bevacizumab in patients with breast

cancer brain metastases. Breast Cancer Research, 22(1).

https://doi.org/10.1186/s13058-020-01372-w
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Lu, Y.-S., Chen, T. W.-W., Lin, C.-H., Yeh, D.-C., Tseng, L.-M., Wu, P.-F., Rau, K.-M.,

Chen, B.-B., Chao, T.-C., Huang, S.-M., Huang, C.-S., Shih, T. T.-F., & Cheng,

A.-L. (2015). Bevacizumab Preconditioning Followed by Etoposide and Cisplatin

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A., Younger, J., Pinho, M. C., Sorensen, A. G., Gerstner, E. R., Harris, G., Krop,

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(2020). Phase II trial of carboplatin and bevacizumab in patients with breast

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https://doi.org/10.1186/s13058-020-01372-w

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The Efficacy and Safety of Eutideron, Etoposide, and Bevacizumab in Patients With

Brain Metastases From Breast Cancer. (2023, March 23). ClinicalTrials.gov.

https://clinicaltrials.gov/ct2/show/NCTXXXXXXXX (Information provided by

Tianjin Medical University Cancer Institute and Hospital - Responsible Party)

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IRBs, Clinical Investigators, and Sponsors. https://www.fda.gov/regulatory-

information/search-fda-guidance-documents/informed-consent.
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