Breast CancerNCT00923104
An Exploratory Evaluation of Biomarkers in Blister Fluid in Healthy Volunteers and Irradiated Skin
An observational study of Breast Cancer and Healthy Volunteer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Blister fluid contains many of the same biomarkers (substances that can be used to determine the effects of certain kinds of treatments) as blood and urine samples, particularly regarding changes in the skin. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Healthy Volunteer, Prostate Cancer
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Apr 2009to 21 Sep 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients in whom radiotherapy is required for standard management of their breast or prostate cancer. Healthy volunteers with no history of cutaneous inflammatory condition of the skin such as eczema, or psoriasis.@@@@@@
Who may be able to join
- Histological diagnosis: Pathologically confirmed diagnosis of 1) invasive breast cancer, 2) ductal carcinoma in situ, or 3) adenocarcinoma of the prostate.
- Patients in whom the management of the histologic diagnosis will include radiation treatment as part of standard clinical management.
- Patients in whom the extent of disease is considered local or locoregional (i.e. requiring definitive radiotherapy to the breast or prostate).
- Patients must be older than 18 years of age.
- Patients must have a primary medical or surgical oncologist in the community or at NCI who is willing to collaborate with the ROB staff in the clinical management of the patient.
- Patients of childbearing or child- fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated with radiotherapy on this study.
Show all 9Show fewer
- Patients must have an ECOG performance status of 0-2 and a life expectancy greater than 12 months.
- Healthy volunteers older than 18 years of age.
- Ability to provide informed consent.
Who cannot join
- Patients with a history of chronic skin disease such as psoriasis, eczema, or history of keloid formation.
- Patients requiring concurrent use of topical steroids
- Patients requiring concurrent use of glucocorticoid therapy.
- Patients who have received topical or systemic chemotherapy within 4 weeks of enrollment (not including hormonal agents such as antiandrogens, GnRH agonists, aromatase inhibitors, tamoxifen, and similar agents) are excluded.
- Patients requiring concurrent chemotherapy with radiotherapy except as noted in (Protocol section 2.3.1) are excluded.
- Patients with a history of lupus erythematosis, scleroderma, ataxia telengiectasia or other known hypersensitivity to therapeutic radiation.
Show all 20Show fewer
- Patients with prior radiotherapy to the site which would be used for blister induction.
- Patients who are pregnant because of the potential mutagenic effects of radiation on a developing fetus or newborn.
- Patients with unrelated systemic illness which in the judgment of the Principal Investigator (PI) would compromise the patient s ability to tolerate this therapy or are likely to interfere with the study procedures or results.
- Patients who are in the estimation of the PI, deemed unable or unlikely to adhere to protocol treatment.
- Patients with significant skin atrophy that would interfere with blister formation.
- Breast cancer patients in whom the site of radiotherapy includes a myocutaneous flap or skin graft.
- ELIGIBILITY CRITERIA FOR HEALTHY VOLUNTEERS:
- History of chronic skin disease such as psoriasis, eczema, or history of keloid formation.
- Concurrent use of glucocorticoid therapy.
- History of lupus erythematosis, scleroderma, ataxia telengiectasia or other known hypersensitivity to therapeutic radiation.
- Prior radiotherapy to the site which would be used for blister induction (for benign or malignant causes).
- Unrelated systemic illness which in the judgment of the Principal Investigator (PI) would compromise the patient s ability to tolerate blister induction or are likely to interfere with blister healing, the study procedures, or the study results.
- Darkly pigmented skin in whom pigmentation changes are a likely complication
- Significant skin atrophy that would interfere with blister formation.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
- Blister fluid contains many of the same biomarkers (substances that can be used to determine the effects of certain kinds of treatments) as blood and urine samples, particularly regarding changes in the skin.
- The Radiation Oncology Branch and others are conducting research studies that require blood and urine samples from healthy volunteers and from patients with cancer. In addition to these samples, researchers would like to collect the fluid from blisters to examine markers of inflammation in the skin.
Read more
Objectives:
- To compare blood, urine, and blister fluid samples of patients with cancer who are undergoing radiation therapy to that of volunteers without cancer who will not be receiving radiation therapy.
- To gather more information about the effects of radiation therapy on the skin and body fluids of individuals.
Eligibility:
- Patients 18 years of age and older who will be receiving radiation therapy for either breast or prostate cancer.
- A separate group of healthy volunteers will also participate in this study.
Design:
- Physical examination and blood samples to determine eligibility for the study.
- Blister induction, conducted before the start of radiation treatment, at completion of radiotherapy (last day of treatment), and at a visit 12 months after the end of radiation treatment.
- Blisters will be created through the use of a suction blister device on the hip (for patients with prostate cancer) or on the treated breast or location of removed breast (for patients with breast cancer).
- Blisters will take approximately 30 minutes to form, and fluid will be removed with a needle and syringe.
- Blood and urine samples will also be collected at this time.
- Radiation treatment for breast or prostate cancer will be conducted according to standard procedures, or as directed by a separate research protocol.
- Evaluations during the treatment period:
- Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
- Blood and urine tests.
- Disease evaluation.
- Post-treatment evaluations:
- Clinic visits at months 1, 3, 6, 9, and 12 after the end of radiation therapy for physical examination and disease assessment.
- Study will end 1 year after the final radiation treatment, upon the collection of the final (third) blister fluid sample.
Read the detailed description
BACKGROUND
Blister fluid has been used to measure cytokine expression, proteomic profiles, and pharmacokinetics in a variety of disease states.
Blister fluid inside radiation treatment fields has been shown to have altered expression of cytokines and products of collagen metabolism.
Evaluation of blister fluid in normal skin inside and outside the radiation field may allow the development of a minimally invasive marker of radiation exposure or damage induced by radiation in irradiated skin.
OBJECTIVES
This protocol will evaluate the ability to determine a cytokine pattern and global changes at the protein level measured in blister fluid that correlates with radiation exposure, absorbed skin dose, or skin toxicity from patients receiving radiation.
ELIGIBILITY
Patients in whom radiotherapy is required for standard management of theirbreast or prostate cancer.
Healthy volunteers with no history of cutaneous inflammatory condition of the skin such as eczema, or psoriasis.
DESIGN
This protocol is designed to evaluate blister fluid in and out of the radiation field in patients that are receiving radiation therapy and in healthy volunteers.
Patients will undergo blister induction and blister fluid collection prior to treatment outside of the radiation field, and after completion of radiation within the radiation field.
Blisters will be induced in a non-sun exposed area and if possible in matched sites (i.e. left and right).
- Conditions
- Breast Cancer, Healthy Volunteer, Prostate Cancer
- Keywords
- Radiation, Blister, Healthy Volunteer, Samples, Natural History, Prostate Cancer, Breast Cancer, HV
- Medical subject headings
- Breast Neoplasms, Prostatic Neoplasms, Blister
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1/healthy volunteers | healthy volunteers | |
| 2/patients | subjects with breast cancer, ductal carcinoma in situ, and adenocarcinoma of prostate |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine if cytokine levels in blister fluid change following exposure of the skin to low or high dose radiation
The primary objectives of this study are (i) to determine if cytokine levels in blister fluid change following exposure of skin to low or high dose radiation, and (ii) to compare cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients. We will examine IL-1 beta, IL6, TNF-alpha, and MMP-1 and -3 for the primary analysis. The remaining cytokines will be examined in secondary analyses.
Measured: study completion
To compare blister fluid cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients
The primary objectives of this study are (i) to determine if cytokine levels in blister fluid change following exposure of skin to low or high dose radiation, and (ii) to compare cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients. We will examine IL-1 beta, IL6, TNF-alpha, and MMP-1 and -3 for the primary analysis. The remaining cytokines will be examined in secondary analyses.
Measured: study completion
Secondary outcomes (6)
To evaluate the reproducibility of cytokine assays in simultaneously collected blister fluid samples from normal patients.
Measured: study completion
To determine if there are differences within circulating and skin proteome and cytokine patterns between participants with cancer and healthy normal controls
Measured: study completion
To determine if cytokine levels and changes at the proteome level measured in blister fluid correlate with absorbed radiation skin dose, acute RTOG skin toxicity (>Grade 3), or late RTOG skin toxicity (>Grade 2).
Measured: study completion
To determine if changes in the proteome in blister fluid occur following exposure of the skin to low or high dose radiation
Measured: study completion
To determine how proteomic pattern changes in skin correlate with circulating proteomic patterns.
Measured: study completion
To determine how cytokine levels in skin correlate with circulating and urinary cytokine levels.
Measured: study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2009 (estimated)
- Study start23 Apr 2009
- Primary completion21 Sep 2017
- Study completion21 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Deborah E Citrin, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00923104
- Sponsor's protocol ID
- 090120
- Other IDs
- 09-C-0120
- Status last verified
- Jun 2025
- First submitted
- 17 Jun 2009
- Last updated
- 8 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request.
Publications
D'Auria L, Pimpinelli F, Ferraro C, D'Ambrogio G, Giacalone B, Bellocci M, Ameglio F. Relationship between theoretical molecular weight and blister fluid/serum ratio of cytokines and five other molecules evaluated in patients with bullous pemphigoid. J Biol Regul Homeost Agents. 1998 Jul-Sep;12(3):76-80.
PubMed 9795835Riekki R, Parikka M, Jukkola A, Salo T, Risteli J, Oikarinen A. Increased expression of collagen types I and III in human skin as a consequence of radiotherapy. Arch Dermatol Res. 2002 Jul;294(4):178-84. doi: 10.1007/s00403-002-0306-2. Epub 2002 Apr 27.
PubMed 12111348Sonesson B, Rosengren E, Hansson AS, Hansson C. UVB-induced inflammation gives increased d-dopachrome tautomerase activity in blister fluid which correlates with macrophage migration inhibitory factor. Exp Dermatol. 2003 Jun;12(3):278-82. doi: 10.1034/j.1600-0625.2003.120307.x.
PubMed 12823441
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Evaluation of Biomarkers in Blister Fluid in Healthy Volunteers and Irradiated Skin
- ClinicalTrials.gov ID
- NCT00923104
- Acronym / sponsor ID
- 090120
- Conditions
- Breast Cancer, Healthy Volunteer, Prostate Cancer
- Keywords
- Radiation, Blister, Healthy Volunteer, Samples, Natural History, Prostate Cancer, Breast Cancer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 23 Apr 2009 (actual)
- Primary completion
- 21 Sep 2017 (actual)
- Study completion
- 21 Sep 2017 (actual)
- First posted
- 18 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Blister fluid contains many of the same biomarkers (substances that can be used to determine the effects of certain kinds of treatments) as blood and urine samples, particularly regarding changes in the skin.
- The Radiation Oncology Branch and others are conducting research studies that require blood and urine samples from healthy volunteers and from patients with cancer. In addition to these samples, researchers would like to collect the fluid from blisters to examine markers of inflammation in the skin.
Objectives:
- To compare blood, urine, and blister fluid samples of patients with cancer who are undergoing radiation therapy to that of volunteers without cancer who will not be receiving radiation therapy.
- To gather more information about the effects of radiation therapy on the skin and body fluids of individuals.
Eligibility:
- Patients 18 years of age and older who will be receiving radiation therapy for either breast or prostate cancer.
- A separate group of healthy volunteers will also participate in this study.
Design:
- Physical examination and blood samples to determine eligibility for the study.
- Blister induction, conducted before the start of radiation treatment, at completion of radiotherapy (last day of treatment), and at a visit 12 months after the end of radiation treatment.
- Blisters will be created through the use of a suction blister device on the hip (for patients with prostate cancer) or on the treated breast or location of removed breast (for patients with breast cancer).
- Blisters will take approximately 30 minutes to form, and fluid will be removed with a needle and syringe.
- Blood and urine samples will also be collected at this time.
- Radiation treatment for breast or prostate cancer will be conducted according to standard procedures, or as directed by a separate research protocol.
- Evaluations during the treatment period:
- Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
- Blood and urine tests.
- Disease evaluation.
- Post-treatment evaluations:
- Clinic visits at months 1, 3, 6, 9, and 12 after the end of radiation therapy for physical examination and disease assessment.
- Study will end 1 year after the final radiation treatment, upon the collection of the final (third) blister fluid sample.
Detailed description
BACKGROUND
Blister fluid has been used to measure cytokine expression, proteomic profiles, and pharmacokinetics in a variety of disease states.
Blister fluid inside radiation treatment fields has been shown to have altered expression of cytokines and products of collagen metabolism.
Evaluation of blister fluid in normal skin inside and outside the radiation field may allow the development of a minimally invasive marker of radiation exposure or damage induced by radiation in irradiated skin.
OBJECTIVES
This protocol will evaluate the ability to determine a cytokine pattern and global changes at the protein level measured in blister fluid that correlates with radiation exposure, absorbed skin dose, or skin toxicity from patients receiving radiation.
ELIGIBILITY
Patients in whom radiotherapy is required for standard management of theirbreast or prostate cancer.
Healthy volunteers with no history of cutaneous inflammatory condition of the skin such as eczema, or psoriasis.
DESIGN
This protocol is designed to evaluate blister fluid in and out of the radiation field in patients that are receiving radiation therapy and in healthy volunteers.
Patients will undergo blister induction and blister fluid collection prior to treatment outside of the radiation field, and after completion of radiation within the radiation field.
Blisters will be induced in a non-sun exposed area and if possible in matched sites (i.e. left and right).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/healthy volunteers | – | –healthy volunteers |
| 2/patients | – | –subjects with breast cancer, ductal carcinoma in situ, and adenocarcinoma of prostate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients in whom radiotherapy is required for standard management of their breast or prostate cancer. Healthy volunteers with no history of cutaneous inflammatory condition of the skin such as eczema, or psoriasis.@@@@@@
Key inclusion criteria (9 listed)
- Histological diagnosis: Pathologically confirmed diagnosis of 1) invasive breast cancer, 2) ductal carcinoma in situ, or 3) adenocarcinoma of the prostate.
- Patients in whom the management of the histologic diagnosis will include radiation treatment as part of standard clinical management.
- Patients in whom the extent of disease is considered local or locoregional (i.e. requiring definitive radiotherapy to the breast or prostate).
- Patients must be older than 18 years of age.
- Patients must have a primary medical or surgical oncologist in the community or at NCI who is willing to collaborate with the ROB staff in the clinical management of the patient.
Key exclusion criteria (20 listed)
- Patients with a history of chronic skin disease such as psoriasis, eczema, or history of keloid formation.
- Patients requiring concurrent use of topical steroids
- Patients requiring concurrent use of glucocorticoid therapy.
- Patients who have received topical or systemic chemotherapy within 4 weeks of enrollment (not including hormonal agents such as antiandrogens, GnRH agonists, aromatase inhibitors, tamoxifen, and similar agents) are excluded.
- Patients requiring concurrent chemotherapy with radiotherapy except as noted in (Protocol section 2.3.1) are excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To determine if cytokine levels in blister fluid change following exposure of the skin to low or high dose radiation
Time frame: study completion
The primary objectives of this study are (i) to determine if cytokine levels in blister fluid change following exposure of skin to low or high dose radiation, and (ii) to compare cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients. We will examine IL-1 beta, IL6, TNF-alpha, and MMP-1 and -3 for the primary analysis. The remaining cytokines will be examined in secondary analyses.
To compare blister fluid cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients
Time frame: study completion
The primary objectives of this study are (i) to determine if cytokine levels in blister fluid change following exposure of skin to low or high dose radiation, and (ii) to compare cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients. We will examine IL-1 beta, IL6, TNF-alpha, and MMP-1 and -3 for the primary analysis. The remaining cytokines will be examined in secondary analyses.
6 secondary outcomes
To evaluate the reproducibility of cytokine assays in simultaneously collected blister fluid samples from normal patients.
Time frame: study completion
To determine if there are differences within circulating and skin proteome and cytokine patterns between participants with cancer and healthy normal controls
Time frame: study completion
To determine if cytokine levels and changes at the proteome level measured in blister fluid correlate with absorbed radiation skin dose, acute RTOG skin toxicity (>Grade 3), or late RTOG skin toxicity (>Grade 2).
Time frame: study completion
To determine if changes in the proteome in blister fluid occur following exposure of the skin to low or high dose radiation
Time frame: study completion
To determine how proteomic pattern changes in skin correlate with circulating proteomic patterns.
Time frame: study completion
To determine how cytokine levels in skin correlate with circulating and urinary cytokine levels.
Time frame: study completion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2025.
- Background: PubMed 9795835D'Auria L, Pimpinelli F, Ferraro C, D'Ambrogio G, Giacalone B, Bellocci M, Ameglio F. Relationship between theoretical molecular weight and blister fluid/serum ratio of cytokines and five other molecules evaluated in patients with bullous pemphigoid. J Biol Regul Homeost Agents. 1998 Jul-Sep;12(3):76-80.
- Background: PubMed 12111348Riekki R, Parikka M, Jukkola A, Salo T, Risteli J, Oikarinen A. Increased expression of collagen types I and III in human skin as a consequence of radiotherapy. Arch Dermatol Res. 2002 Jul;294(4):178-84. doi: 10.1007/s00403-002-0306-2. Epub 2002 Apr 27.
- Background: PubMed 12823441Sonesson B, Rosengren E, Hansson AS, Hansson C. UVB-induced inflammation gives increased d-dopachrome tautomerase activity in blister fluid which correlates with macrophage migration inhibitory factor. Exp Dermatol. 2003 Jun;12(3):278-82. doi: 10.1034/j.1600-0625.2003.120307.x.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah E Citrin, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer and Healthy Volunteer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine if cytokine levels in blister fluid change following exposure of the skin to low or high dose radiation (time frame: study completion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00923104, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2025.