Breast NeoplasmsNCT00355316
A Study to Determine the Clinical Significance of Molecular Detection of Breast Cancer in the Blood of Stage IV Breast Cancer Patients
A study testing Blood draw in people with Breast Neoplasms, run by Washington University School of Medicine at 2 sites in United States.
Trial summary
This study is designed to determine whether molecular detection of breast cancer cells in the peripheral blood of Stage IV breast cancer patients is a clinically relevant predictor of progression-free and overall survival. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Blood draw
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2005to Feb 2013
- Phase
- Interventional
- 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
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patient age must be > 21 years.
- Patient must have a tissue diagnosis of invasive breast cancer.
- Patient must have documented evidence of metastatic disease.
- Patient must have measurable lesions.
- Patients must be initiating systemic therapy. Patients receiving hormonal therapy, and/or chemotherapy alone or in combination with other therapies are eligible.
- Patient must have an ECOG performance status of 0, 1, or 2.
Show all 14Show fewer
- Patient must be available for follow-up.
- Patient or their authorized legally acceptable representative must consent to be in the study and must have signed and dated an approved consent form which conforms to federal and institutional guidelines.
- The patient with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patients have been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).
- A volunteer will be eligible for inclusion in this study only if ALL of the following criteria apply:
- Volunteer age must be > 21 years.
- Volunteer or their authorized legally acceptable representative must consent to be in the study and must have signed and dated an approved consent form which conforms to federal and institutional guidelines.
- Patients with benign breast disease are eligible for enrollment.
- The volunteer with a previous history of non-breast malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided both of the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patient has been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).
Who cannot join
- A patient will be ineligible for inclusion in this study if ANY of the following criteria apply:
- No documented metastatic disease.
- No measurable lesions.
- Bone only and/or brain metastasis.
- Patient is not initiating a new regimen of systemic therapy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Medical University of South Carolina
Charleston, South Carolina, 29425
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Peripheral Blood Molecular Staging of Breast Cancer: A Prospective Cohort Study Designed to Determine the Clinical Significance of Molecular Detection of Breast Cancer in the Peripheral Blood of Stage IV Breast Cancer Patients
This study is designed to determine whether molecular detection of breast cancer cells in the peripheral blood of Stage IV breast cancer patients is a clinically relevant predictor of progression-free and overall survival. Stage IV breast cancer patients who have measurable breast cancer metastases and are initiating a regimen of systemic therapy are eligible for enrollment. Multi-marker real-time RT-PCR analysis will be performed on peripheral blood specimens from 92 breast cancer patients and 120 healthy volunteers. Peripheral blood specimens from breast cancer patients will be obtained at the time of study entry (prior to initiation of systemic therapy) and at serial time points during follow-up. Subjects will be followed longitudinally until death, although the study has been powered so that the primary objective can be addressed after 12 months of follow-up. Healthy volunteers will be asked to provide a blood sample at time of enrollment but will not be followed.
- Conditions
- Breast Neoplasms
- Being tested
- Blood draw
- Keywords
- Breast Cancer, Peripheral, Blood
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood drawOther
| Study group | Role | What they receive |
|---|---|---|
| Stage IV Breast Cancer | Experimental | Blood draws at baseline before systemic therapy. Blood draw then every 6 weeks for approximately 12 weeks. Receives: Other: Blood draw |
| Healthy Volunteers | Other | Baseline blood draw. Receives: Other: Blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
The prevalence of breast cancer cells in the peripheral blood
Specifically, it is predicted that 60% of subjects with Stage IV breast cancer will have evidence of breast cancer cells in the peripheral blood by multi-marker real-time RT-PCR analysis, and that these subjects will experience a significantly decreased progression-free and overall survival.
Measured: 1 year
Secondary outcomes (3)
Evaluate the prognostic significance of molecular detection of breast cancer cells in peripheral blood after initiation of systemic therapy.
Specifically, we will determine if molecular detection of circulating breast cancer cells after the initiation of systemic therapy is associated with a significantly decreased progression-free and overall survival.
Measured: Until patient death
Quantify baseline molecular marker expression levels in the peripheral blood of healthy volunteers
Determine if baseline molecular marker expression levels are dependent on patient age, race, and/or the presence of benign breast disease.
Measured: Approximately 12 weeks
Compare molecular analyses to the results of the CellSeach assay
Measured: Approximately 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2006 (estimated)
- Study startNov 2005
- Primary completionNov 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (80)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- William E. Gillanders, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00355316
- Sponsor's protocol ID
- 05-0435 / 201109033
- Status last verified
- Jun 2013
- First submitted
- 19 Jul 2006
- Last updated
- 21 Jun 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Valagussa P, Bonadonna G, Veronesi U. Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients. Cancer. 1978 Mar;41(3):1170-8. doi: 10.1002/1097-0142(197803)41:33.0.co;2-i.
PubMed 638961Ghossein RA, Carusone L, Bhattacharya S. Review: polymerase chain reaction detection of micrometastases and circulating tumor cells: application to melanoma, prostate, and thyroid carcinomas. Diagn Mol Pathol. 1999 Dec;8(4):165-75. doi: 10.1097/00019606-199912000-00001.
PubMed 10617272Diel IJ, Kaufmann M, Goerner R, Costa SD, Kaul S, Bastert G. Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis. J Clin Oncol. 1992 Oct;10(10):1534-9. doi: 10.1200/JCO.1992.10.10.1534.
PubMed 1403032Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004 Oct 15;10(20):6897-904. doi: 10.1158/1078-0432.CCR-04-0378.
PubMed 15501967Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004 Aug 19;351(8):781-91. doi: 10.1056/NEJMoa040766.
PubMed 15317891Baker MK, Mikhitarian K, Osta W, Callahan K, Hoda R, Brescia F, Kneuper-Hall R, Mitas M, Cole DJ, Gillanders WE. Molecular detection of breast cancer cells in the peripheral blood of advanced-stage breast cancer patients using multimarker real-time reverse transcription-polymerase chain reaction and a novel porous barrier density gradient centrifugation technology. Clin Cancer Res. 2003 Oct 15;9(13):4865-71.
PubMed 14581359Berns EM, Klijn JG, van Putten WL, van Staveren IL, Portengen H, Foekens JA. c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res. 1992 Mar 1;52(5):1107-13.
PubMed 1737370Datta YH, Adams PT, Drobyski WR, Ethier SP, Terry VH, Roth MS. Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol. 1994 Mar;12(3):475-82. doi: 10.1200/JCO.1994.12.3.475.
PubMed 7509852Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, Matsubara I, Vinante O, Bonoldi E, Boracchi P, Gatti C, Suzuki H, Tominaga T. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997 Jan 15;89(2):139-47. doi: 10.1093/jnci/89.2.139.
PubMed 8998183Ioachim E, Kamina S, Athanassiadou S, Agnantis NJ. The prognostic significance of epidermal growth factor receptor (EGFR), C-erbB-2, Ki-67 and PCNA expression in breast cancer. Anticancer Res. 1996 Sep-Oct;16(5B):3141-7.
PubMed 8920782Anan K, Morisaki T, Katano M, Ikubo A, Tsukahara Y, Kojima M, Uchiyama A, Kuroki S, Torisu M, Tanaka M. Assessment of c-erbB2 and vascular endothelial growth factor mRNA expression in fine-needle aspirates from early breast carcinomas: pre-operative determination of malignant potential. Eur J Surg Oncol. 1998 Feb;24(1):28-33. doi: 10.1016/s0748-7983(98)80121-2.
PubMed 9542512Bieche I, Lazar V, Nogues C, Poynard T, Giovangrandi Y, Bellet D, Lidereau R, Vidaud M. Prognostic value of chorionic gonadotropin beta gene transcripts in human breast carcinoma. Clin Cancer Res. 1998 Mar;4(3):671-6.
PubMed 9533536Harbeck N, Dettmar P, Thomssen C, Henselmann B, Kuhn W, Ulm K, Janicke F, Hofler H, Graeff H, Schmitt M. Prognostic impact of tumor biological factors on survival in node-negative breast cancer. Anticancer Res. 1998 May-Jun;18(3C):2187-97.
PubMed 9703782Linderholm B, Tavelin B, Grankvist K, Henriksson R. Vascular endothelial growth factor is of high prognostic value in node-negative breast carcinoma. J Clin Oncol. 1998 Sep;16(9):3121-8. doi: 10.1200/JCO.1998.16.9.3121.
PubMed 9738584Lockett MA, Baron PL, O'Brien PH, Elliott BM, Robison JG, Maitre N, Metcalf JS, Cole DJ. Detection of occult breast cancer micrometastases in axillary lymph nodes using a multimarker reverse transcriptase-polymerase chain reaction panel. J Am Coll Surg. 1998 Jul;187(1):9-16. doi: 10.1016/s1072-7515(98)00130-6.
PubMed 9660019
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peripheral Blood Molecular Staging of Breast Cancer: A Prospective Cohort Study Designed to Determine the Clinical Significance of Molecular Detection of Breast Cancer in the Peripheral Blood of Stage IV Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT00355316
- Acronym / sponsor ID
- 05-0435 / 201109033
- Conditions
- Breast Neoplasms
- Keywords
- Breast Cancer, Peripheral, Blood
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Nov 2005
- Primary completion
- Nov 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 21 Jul 2006 (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.
This study is designed to determine whether molecular detection of breast cancer cells in the peripheral blood of Stage IV breast cancer patients is a clinically relevant predictor of progression-free and overall survival. Stage IV breast cancer patients who have measurable breast cancer metastases and are initiating a regimen of systemic therapy are eligible for enrollment. Multi-marker real-time RT-PCR analysis will be performed on peripheral blood specimens from 92 breast cancer patients and 120 healthy volunteers. Peripheral blood specimens from breast cancer patients will be obtained at the time of study entry (prior to initiation of systemic therapy) and at serial time points during follow-up. Subjects will be followed longitudinally until death, although the study has been powered so that the primary objective can be addressed after 12 months of follow-up. Healthy volunteers will be asked to provide a blood sample at time of enrollment but will not be followed.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage IV Breast Cancer | Experimental | Other: Blood drawBlood draws at baseline before systemic therapy. Blood draw then every 6 weeks for approximately 12 weeks. |
| Healthy Volunteers | Other | Other: Blood drawBaseline blood draw. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patient age must be > 21 years.
- Patient must have a tissue diagnosis of invasive breast cancer.
- Patient must have documented evidence of metastatic disease.
- Patient must have measurable lesions.
- Patients must be initiating systemic therapy. Patients receiving hormonal therapy, and/or chemotherapy alone or in combination with other therapies are eligible.
Key exclusion criteria (5 listed)
- A patient will be ineligible for inclusion in this study if ANY of the following criteria apply:
- No documented metastatic disease.
- No measurable lesions.
- Bone only and/or brain metastasis.
- Patient is not initiating a new regimen of systemic therapy.
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 |
|---|---|---|
| Blood draw | Other | Healthy Volunteers, Stage IV Breast Cancer |
Primary outcome
The prevalence of breast cancer cells in the peripheral blood
Time frame: 1 year
Specifically, it is predicted that 60% of subjects with Stage IV breast cancer will have evidence of breast cancer cells in the peripheral blood by multi-marker real-time RT-PCR analysis, and that these subjects will experience a significantly decreased progression-free and overall survival.
3 secondary outcomes
Evaluate the prognostic significance of molecular detection of breast cancer cells in peripheral blood after initiation of systemic therapy.
Time frame: Until patient death
Quantify baseline molecular marker expression levels in the peripheral blood of healthy volunteers
Time frame: Approximately 12 weeks
Compare molecular analyses to the results of the CellSeach assay
Time frame: Approximately 12 weeks
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 21 Jun 2013.
- Background: PubMed 638961Valagussa P, Bonadonna G, Veronesi U. Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients. Cancer. 1978 Mar;41(3):1170-8. doi: 10.1002/1097-0142(197803)41:33.0.co;2-i.
- Background: PubMed 10617272Ghossein RA, Carusone L, Bhattacharya S. Review: polymerase chain reaction detection of micrometastases and circulating tumor cells: application to melanoma, prostate, and thyroid carcinomas. Diagn Mol Pathol. 1999 Dec;8(4):165-75. doi: 10.1097/00019606-199912000-00001.
- Background: PubMed 1403032Diel IJ, Kaufmann M, Goerner R, Costa SD, Kaul S, Bastert G. Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis. J Clin Oncol. 1992 Oct;10(10):1534-9. doi: 10.1200/JCO.1992.10.10.1534.
- Background: PubMed 15501967Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004 Oct 15;10(20):6897-904. doi: 10.1158/1078-0432.CCR-04-0378.
- Background: PubMed 15317891Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, Hayes DF. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004 Aug 19;351(8):781-91. doi: 10.1056/NEJMoa040766.
- Background: PubMed 14581359Baker MK, Mikhitarian K, Osta W, Callahan K, Hoda R, Brescia F, Kneuper-Hall R, Mitas M, Cole DJ, Gillanders WE. Molecular detection of breast cancer cells in the peripheral blood of advanced-stage breast cancer patients using multimarker real-time reverse transcription-polymerase chain reaction and a novel porous barrier density gradient centrifugation technology. Clin Cancer Res. 2003 Oct 15;9(13):4865-71.
- Background: PubMed 1737370Berns EM, Klijn JG, van Putten WL, van Staveren IL, Portengen H, Foekens JA. c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res. 1992 Mar 1;52(5):1107-13.
- Background: PubMed 7509852Datta YH, Adams PT, Drobyski WR, Ethier SP, Terry VH, Roth MS. Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction. J Clin Oncol. 1994 Mar;12(3):475-82. doi: 10.1200/JCO.1994.12.3.475.
- Background: PubMed 8998183Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, Matsubara I, Vinante O, Bonoldi E, Boracchi P, Gatti C, Suzuki H, Tominaga T. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997 Jan 15;89(2):139-47. doi: 10.1093/jnci/89.2.139.
- Background: PubMed 8920782Ioachim E, Kamina S, Athanassiadou S, Agnantis NJ. The prognostic significance of epidermal growth factor receptor (EGFR), C-erbB-2, Ki-67 and PCNA expression in breast cancer. Anticancer Res. 1996 Sep-Oct;16(5B):3141-7.
- Background: PubMed 9542512Anan K, Morisaki T, Katano M, Ikubo A, Tsukahara Y, Kojima M, Uchiyama A, Kuroki S, Torisu M, Tanaka M. Assessment of c-erbB2 and vascular endothelial growth factor mRNA expression in fine-needle aspirates from early breast carcinomas: pre-operative determination of malignant potential. Eur J Surg Oncol. 1998 Feb;24(1):28-33. doi: 10.1016/s0748-7983(98)80121-2.
- Background: PubMed 9533536Bieche I, Lazar V, Nogues C, Poynard T, Giovangrandi Y, Bellet D, Lidereau R, Vidaud M. Prognostic value of chorionic gonadotropin beta gene transcripts in human breast carcinoma. Clin Cancer Res. 1998 Mar;4(3):671-6.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
Related trials for Breast Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
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.
William E. Gillanders, M.D. principal investigator
Washington University School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood draw in people with Breast Neoplasms, run by Washington University School of Medicine at 2 sites 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 14 inclusion and 5 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 21 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The prevalence of breast cancer cells in the peripheral blood (time frame: 1 year). 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 NCT00355316, which also lists 80 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 21 Jun 2013.