Breast CancerNCT01814449
Relationship Between Hypoxia and Endocrine Response in Human Breast Cancer
An observational study of Breast Cancer and Hypoxia, run by Fudan University at 1 site in China.
Trial summary
The aim of our current study was to analyze whether 18F-labeled Fluoromisonidazole (1-(2-nitro-1-imidazolyl)- 2-hydroxy-3-fluoropropane [18F-FMISO]) PET/CT and expression of HIF-1-alpha could predict response of primary endocrine therapy in ER-positive breast cancer Read more about this study
- Who is it for?
- Ages 60 to 90 years, women only
- Conditions the study is for
- Breast Cancer, Hypoxia
- What is being tested?
- 18FMISO PET/CT scan and Letrozole
- Type of treatment
- Injection or infusion
- How many people
- 130 participants
- Where
- 1 siteChina
- Study dates
- Mar 2012to May 2014
- How long will I take part?
- 6 Months
- 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 60 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Postmenopausal women who had ER-a-positive breast cancer at stages II-IV and had never received prior endocrine therapy were considered eligible for this study.
Who may be able to join
- Postmenopausal female
- With primary invasive ER positive breast cancer pathologically approved by core needle biopsy
- The target lesion must be measurable and maximum diameter should be over 2cm.
- Require and accept Endocrine therapy
- Never treated with endocrine therapy before
- Patients must have an ECOG performance status of 0 to 2
- Leucocyte count must be ≥ 3.0*10^9/L and platelet count must be ≥ 40*10^9/L; AST/SGOT or ALT/AGPT must be < 2 times the ULN; serum creatinine must be < 2 times the ULN
Who cannot join
- Patients with brain and liver metastasis
- Previous history of severe heart dysfunction (above Class III), infection, osteoporosis, bone related event or disease in endocrine system
- Combination of other anticancer therapy, with the exception of biphosphonate
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Cancer Hospital/ Institute, Fudan University
Shanghai, Shanghai Municipality, 200032
Zhimin Shao, M.D., 862164175590 ext. 8808, zhimingshao@yahoo.com
About this study
Official title: Department of Breast Surgery And Department of Nuclear Medicine, Fudan University Shanghai Cancer Center,
The aim of our current study was to analyze whether 18F-labeled Fluoromisonidazole (1-(2-nitro-1-imidazolyl)- 2-hydroxy-3-fluoropropane [18F-FMISO]) PET/CT and expression of HIF-1-alpha could predict response of primary endocrine therapy in ER-positive breast cancer
Read the detailed description
Approximately 30% of ER-positive breast cancer will unfortunately display primary resistance to hormonal therapy, and some may develop acquired resistance to the therapy after initial treatment. Hypoxia is a normal phenomenon in solid tumors that arises, in part, from uncontrolled proliferation and immature blood vessels. Previous studies have demonstrated hypoxia significantly reduced both the growth-promoting effects of estradiol (E2) and the growth-inhibitory effects of an antiestrogen on ER-positive breast cancer cell lines. A recent study comparing neoadjuvant letrozole with letrozole plus metronomic cyclophosphamide found that increased levels of HIF-1a were significantly associated with resistance to treatment. Taken together, these data indicate that hypoxia might be associated with endocrine resistance in breast cancer.
With PET/CT, radiolabeled hypoxia-avid compounds can be applied to evaluate oxygenation status in experimental or human tumors. 18F-labeled fluoromisonidazole (1-[2-nitro- 1-imidazolyl]-2-hydroxy-3-fluoropropane [18F-FMISO]) PET/CT is the most widely used one in the clinic. Studies have demonstrated an excellent correlation between the 18F-FMISO uptake and oxygenation status of several cancers including breast cancer.
The major aim of our study was to analyze uptake of 18FFMISO as well as the IHC expression of HIF-1-alpha in ER-positive breast cancers, and to predict the clinical, pathological and biological response of primary endocrine therapy.
- Conditions
- Breast Cancer, Hypoxia
- Being tested
- 18FMISO PET/CT scan, Letrozole
- Keywords
- Breast cancer, Hypoxia, Hypoxia related gene, Endocrine therapy, Treatment resistance
- Medical subject headings
- Breast Neoplasms, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
18FMISO PET/CT scanOther
The baseline 18F-FMISO PET/CT scans were scheduled before initiation of endocrine therapy. All patients were injected intravenously with 370 MBq of 18F-FMISO and PET/CT static emission scans were conducted at 4 hours after injection.
LetrozoleDrug
Patients were assigned to primary endocrine therapy with letrozole 2.5mg daily for at least 4 months.
| Study group | Role | What they receive |
|---|---|---|
| Hypoxic Group | Higher 18FMISO uptake (Target to background Ratio, TBR>1.2) in Primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy Letrozole was given to the patients. Receives: Other: 18FMISO PET/CT scan; Drug: Letrozole | |
| Non-Hypoxic Group | Lower 18FMISO uptake (TBR<1.2)in primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy letrozole was given to the patients. Receives: Other: 18FMISO PET/CT scan; Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Objective Response
Tumor response was evaluated according to the criteria of the World Health Organization. Clinical tumor progression (PD) was defined as an increase of at least 25% in tumor size; stable disease (SD) as an increase of less than 25% or a reduction of less than 50%; partial response (cPR) as a tumor shrinkage greater than 50%; and complete response (cCR) as the complete disappearance of all clinical signs of disease.
Measured: 4 months
Secondary outcomes (2)
Pathological Response
Including pathological complete response (pCR or Grade 5),pathological partial response (pPR or Grade 3-4) and pathological non-response (NR or Grade 1-2).
Measured: 4 months
Depression of Ki67 score
A biological response of Ki67 depression was tested on a second core needly biopsy on the primary site of the breast cancer after 3 months of primary endocrine therapy. Ki67>=15% was regarded as a biological resistance to primary endocrine therapy
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2013 (estimated)
- Study startMar 2012
- Primary completionFeb 2014 (estimated)
- Study completionMay 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 130 participants (estimated)
- Target duration
- 6 Months
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guangyu Liu, Fudan University
- Investigators
- Guangyu Liu, M.D., Principal investigator, Cancer Hospital/Institute,Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01814449
- Sponsor's protocol ID
- 20120224.1.1
- Status last verified
- Mar 2013
- First submitted
- 16 Mar 2013
- Last updated
- 20 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Department of Breast Surgery And Department of Nuclear Medicine, Fudan University Shanghai Cancer Center,
- ClinicalTrials.gov ID
- NCT01814449
- Acronym / sponsor ID
- 20120224.1.1
- Conditions
- Breast Cancer, Hypoxia
- Keywords
- Breast cancer, Hypoxia, Hypoxia related gene, Endocrine therapy, Treatment resistance
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Feb 2014 (estimated)
- Study completion
- May 2014 (estimated)
- First posted
- 20 Mar 2013 (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.
The aim of our current study was to analyze whether 18F-labeled Fluoromisonidazole (1-(2-nitro-1-imidazolyl)- 2-hydroxy-3-fluoropropane [18F-FMISO]) PET/CT and expression of HIF-1-alpha could predict response of primary endocrine therapy in ER-positive breast cancer
Detailed description
Approximately 30% of ER-positive breast cancer will unfortunately display primary resistance to hormonal therapy, and some may develop acquired resistance to the therapy after initial treatment. Hypoxia is a normal phenomenon in solid tumors that arises, in part, from uncontrolled proliferation and immature blood vessels. Previous studies have demonstrated hypoxia significantly reduced both the growth-promoting effects of estradiol (E2) and the growth-inhibitory effects of an antiestrogen on ER-positive breast cancer cell lines. A recent study comparing neoadjuvant letrozole with letrozole plus metronomic cyclophosphamide found that increased levels of HIF-1a were significantly associated with resistance to treatment. Taken together, these data indicate that hypoxia might be associated with endocrine resistance in breast cancer.
With PET/CT, radiolabeled hypoxia-avid compounds can be applied to evaluate oxygenation status in experimental or human tumors. 18F-labeled fluoromisonidazole (1-[2-nitro- 1-imidazolyl]-2-hydroxy-3-fluoropropane [18F-FMISO]) PET/CT is the most widely used one in the clinic. Studies have demonstrated an excellent correlation between the 18F-FMISO uptake and oxygenation status of several cancers including breast cancer.
The major aim of our study was to analyze uptake of 18FFMISO as well as the IHC expression of HIF-1-alpha in ER-positive breast cancers, and to predict the clinical, pathological and biological response of primary endocrine therapy.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 6 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypoxic Group | – | Other: 18FMISO PET/CT scan, Drug: LetrozoleHigher 18FMISO uptake (Target to background Ratio, TBR>1.2) in Primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy Letrozole was given to the patients. |
| Non-Hypoxic Group | – | Other: 18FMISO PET/CT scan, Drug: LetrozoleLower 18FMISO uptake (TBR<1.2)in primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy letrozole was given to the patients. |
Who may qualify
- Ages
- 60 to 90 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Postmenopausal women who had ER-a-positive breast cancer at stages II-IV and had never received prior endocrine therapy were considered eligible for this study.
Key inclusion criteria (7 listed)
- Postmenopausal female
- With primary invasive ER positive breast cancer pathologically approved by core needle biopsy
- The target lesion must be measurable and maximum diameter should be over 2cm.
- Require and accept Endocrine therapy
- Never treated with endocrine therapy before
Key exclusion criteria (3 listed)
- Patients with brain and liver metastasis
- Previous history of severe heart dysfunction (above Class III), infection, osteoporosis, bone related event or disease in endocrine system
- Combination of other anticancer therapy, with the exception of biphosphonate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 18FMISO PET/CT scanThe baseline 18F-FMISO PET/CT scans were scheduled before initiation of endocrine therapy. All patients were injected intravenously with 370 MBq of 18F-FMISO and PET/CT static emission scans were conducted at 4 hours after injection. | Other | Hypoxic Group, Non-Hypoxic Group |
| LetrozolePatients were assigned to primary endocrine therapy with letrozole 2.5mg daily for at least 4 months. | Drug | Hypoxic Group, Non-Hypoxic Group |
Primary outcome
Clinical Objective Response
Time frame: 4 months
Tumor response was evaluated according to the criteria of the World Health Organization. Clinical tumor progression (PD) was defined as an increase of at least 25% in tumor size; stable disease (SD) as an increase of less than 25% or a reduction of less than 50%; partial response (cPR) as a tumor shrinkage greater than 50%; and complete response (cCR) as the complete disappearance of all clinical signs of disease.
2 secondary outcomes
Pathological Response
Time frame: 4 months
Depression of Ki67 score
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2013.
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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.
Guangyu Liu, M.D. principal investigator
Cancer Hospital/Institute,Fudan University
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 Hypoxia, run by Fudan University at 1 site in China.
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 7 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 20 Mar 2013. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guangyu Liu, M.D. (86-21-64175590 ext. 8808, liugy123@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Objective Response (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Mar 2013.