Breast CancerPhase 2PROMIXNCT00957125
A Translational Trial on Molecular Markers and Functional Imaging to Predict Response of Preoperative Treatment of Breast Cancer Early
A Phase 2 study testing Epirubicin, Docetaxel and Bevacizumab in people with Breast Cancer, run by Thomas Hatschek at 6 sites in Sweden.
Trial summary
Patients with localized primary breast cancer including inflammatory breast cancer suitable for primary medical treatment and/or regional lymph node metastases receive six cycles of chemotherapy with epirubicin and docetaxel. Treatment evaluations are performed after the second, fourth and sixth cycle. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Epirubicin, Docetaxel and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 6 sitesSweden
- Study dates
- Sep 2008to Nov 2016
- Phase
- Phase 2
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Female patients with breast cancer confirmed by histology.
- Tumour and blood samples according to APPENDIX I available.
- Age 18 years or older. Elderly patients in condition adequate for chemotherapy.
- Localized primary breast cancer including inflammatory breast cancer suitable for primary medical treatment and/or regional lymph node metastases including ipsilateral supraclavicular nodes with breast cancer diagnosis confirmed by histological examination with or without breast tumour lesions.
- Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders.
- ECOG performance status 0-1.
- Patients in child-bearing age with adequate contraception.
Who cannot join
- Distant metastases, including node metastases in the contralateral breast region and in the mediastina.
- Other malignancy for the last two years except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix.
- HER2-amplification verified by FISH analysis.
- Pregnancy or lactation.
- Uncontrolled hypertension, heart, liver, kidney related or other medical or psychiatric disorders.
- Recent history of thromboembolism and ongoing medication with full-dose anticoagulants.
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- Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrollment or anticipation of the need for major surgery during study treatment.
- Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion.
- History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
- Non-healing wound, active peptic ulcer or bone fracture.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrollment.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Sweden6 sites
Sahlgrenska University Hospital
Gothenburg
Lund University Hospital
Lund
Malmö General University Hospital
Malmö
Karolinska University Hospital, Dept of Oncology
Stockholm, SE-17176
County Hospital
Sundsvall
Uppsala University Hospital
Uppsala
About this study
Official title: PROMIX - Preoperative Treatment of Breast Cancer With a Combination of Epirubicin, Docetaxel and Bevacizumab. A Translational Trial on Molecular Markers and Functional Imaging to Predict Response Early. A Phase 2 Study.
Patients with localized primary breast cancer including inflammatory breast cancer suitable for primary medical treatment and/or regional lymph node metastases receive six cycles of chemotherapy with epirubicin and docetaxel. Treatment evaluations are performed after the second, fourth and sixth cycle. In case of SD/PR after the second course, bevacizumab is added to the combination for the remaining four courses.
Besides standard response evaluation clinically and by mammography and ultrasound, several functional imaging techniques including MR, CT-PET and contrast-enhanced ultrasound are investigated. Fresh tumor tissue samples from the primary tumor are collected before start, after two courses and in connection with surgery. The aim of the trial is to detect biological factors and functional imaging techniques with the ability to predict response at an early stage of treatment.
Read the detailed description
Primary endpoints: Objective response (OR) characterized by conventional radiological and functional imaging procedures and biological tumour markers at an early point of treatment with epirubicin + docetaxel and effects of addition of bevacizumab as reflected by these procedures. Early functional and biological changes signalling pathological complete response (pCR). Secondary endpoints: Secondary endpoints: Morphological and biological changes of tumours exposed for cytotoxic and targeted treatment. Disease-free survival. Safety.
Evaluations:
Before start of treatment:
Tumour staging: Bone scan, chest X-ray and liver ultrasound or CT scan of chest and abdomen within four weeks before start of treatment. Physical examination, conventional radiology (ultrasound and mammography including pre-treatment localization with carbon suspension) and functional imaging procedure (MRI or PET-CT or Contrast-Enhanced Ultrasound (CEUS) or Scintigraphy with 99m-Tc-HMPAO (Ceretec)) within two weeks before start of treatment.
Blood samples (SNP, metabolomics, M-30 assay, TK/XPA-210 assay, angiogenesis markers, TIMP-1, tissue factor) and tumour biopsies (transcriptomics, proteomics, IHC-stroma, AMOT) are collected within two weeks before start of treatment.
During treatment:
Physical examination before start of each treatment. Imaging procedures: Mammography, ultrasound (compulsory) one week (5-9 days) after cycles 2, 4 and 6. MRI, PET-CT, Contrast-Enhanced Ultrasound (CEUS) applied according to availability at the participating sites, one week (5-9 days) after cycles 2 and 4.
Tumour markers: Blood samples (proteomics, metabolomics, M-30 assay, TK/XPA-210 assay, angiogenesis markers, TIMP-1, tissue factor) are collected 48 hours after cycles 1 thru 4. Tumour tissue (transcriptomics, proteomics, IHC-stroma, AMOT) is taken charge of by biopsy one week (5-9 days) after cycle 2 and from the tumour specimen in connection with surgery.
Totally, 150-200 patients with measurable/evaluable primary breast cancer are planned for inclusion within a period of two years time. For each imaging method, approximately 40-50 patients will be included. The study is designed to find early predictors of response by testing a set-up of several different molecular and imaging tools. In addition, for each method changes of patterns occurring during treatment will be compared to baseline findings and, in the case of functional imaging, standard imaging procedures.
All patients will be followed for five years after operation with regard to outcome and toxicity.
- Conditions
- Breast Cancer
- Being tested
- Epirubicin, Docetaxel, Bevacizumab
- Keywords
- Localized primary breast cancer, Inflammatory breast cancer
- Medical subject headings
- Breast Neoplasms, Inflammatory Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpirubicinDrug
75 mg/m2 i.v. infusion, 30 min, cycle day 1, cycles 1-6.
DocetaxelDrug
Also called Taxotere
75 mg/m2 i.v. infusion, 60 min, cycles day 1, cycle 1-6.
BevacizumabDrug
Also called Avastin
15 mg/kg, i.v. infusion, 90 min, cycle day 1, cycles 3-6 if PR or SD after cycle 2.
| Study group | Role | What they receive |
|---|---|---|
| Epirubicin Docetaxel Bevacizumab | Experimental | Epirubicin and docetaxel i.v. infusion q 3 weeks for 2 cycles.
* If complete response this treatment continues for 4 cycles, totally 6 cycles.
* If partial response or stable disease, epirubicin and docetaxel and bevacizumab i.v. infusion q 3 weeks for 4 cycles.
* If progressive disease after the first 2 cycles individualized treatment. Receives: Drug: Epirubicin; Drug: Docetaxel; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the sensitivity and of defined diagnostic and biological procedures to detect response/non-response to neoadjuvant treatment at an early point among patients with breast cancer.
Measured: 6 weeks
Secondary outcomes (5)
Identification of tumour characteristics and treatment-related changes of tumour characteristics predictive of long-term prognosis.
Measured: 5 years
Comparison between the standard evaluation procedures mammography, conventional ultrasound and clinical examination and functional imaging techniques and biological procedures with emphasis on detection of response at an early point of treatment.
Measured: 6 weeks
Studies on the addition of bevacizumab with regard to further improvement of response in tumours with stable (SD) or partial response (PR) and the impact of treatment on angiogenesis and local features of the tumour environment.
Measured: 6 weeks
Acute toxicity
Measured: 6 weeks after last chemotherapy
Late toxicity
Measured: 5 years after last chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2009 (estimated)
- Study startSep 2008
- Primary completionNov 2011
- Study completionNov 2016 (estimated)
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Hatschek
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Thomas Hatschek, Karolinska University Hospital
- Investigators
- Thomas Hatschek, MD, PhD, Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00957125
- Sponsor's protocol ID
- PROMIX
- Other IDs
- 2007-005858-23
- Acronym
- PROMIX
- Status last verified
- Sep 2016
- First submitted
- 10 Aug 2009
- Last updated
- 8 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Saracco A, Szabo BK, Tanczos E, Bergh J, Hatschek T. Contrast-enhanced ultrasound (CEUS) in assessing early response among patients with invasive breast cancer undergoing neoadjuvant chemotherapy. Acta Radiol. 2017 Apr;58(4):394-402. doi: 10.1177/0284185116658322. Epub 2016 Jul 28.
PubMed 27461224Tribukait B. Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume. BMC Cancer. 2020 May 18;20(1):440. doi: 10.1186/s12885-020-06925-y.
PubMed 32423477Nakamura M, Zhang Y, Yang Y, Sonmez C, Zheng W, Huang G, Seki T, Iwamoto H, Ding B, Yin L, Foukakis T, Hatschek T, Li X, Hosaka K, Li J, Yu G, Wang X, Liu Y, Cao Y. Off-tumor targets compromise antiangiogenic drug sensitivity by inducing kidney erythropoietin production. Proc Natl Acad Sci U S A. 2017 Nov 7;114(45):E9635-E9644. doi: 10.1073/pnas.1703431114. Epub 2017 Oct 23.
PubMed 29078273
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PROMIX - Preoperative Treatment of Breast Cancer With a Combination of Epirubicin, Docetaxel and Bevacizumab. A Translational Trial on Molecular Markers and Functional Imaging to Predict Response Early. A Phase 2 Study.
- ClinicalTrials.gov ID
- NCT00957125
- Acronym / sponsor ID
- PROMIX / PROMIX
- Conditions
- Breast Cancer
- Keywords
- Localized primary breast cancer, Inflammatory breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 151 participants (actual)
- Lead sponsor
- Thomas HatschekUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2016 (estimated)
- First posted
- 12 Aug 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.
Patients with localized primary breast cancer including inflammatory breast cancer suitable for primary medical treatment and/or regional lymph node metastases receive six cycles of chemotherapy with epirubicin and docetaxel. Treatment evaluations are performed after the second, fourth and sixth cycle. In case of SD/PR after the second course, bevacizumab is added to the combination for the remaining four courses.
Besides standard response evaluation clinically and by mammography and ultrasound, several functional imaging techniques including MR, CT-PET and contrast-enhanced ultrasound are investigated. Fresh tumor tissue samples from the primary tumor are collected before start, after two courses and in connection with surgery. The aim of the trial is to detect biological factors and functional imaging techniques with the ability to predict response at an early stage of treatment.
Detailed description
Primary endpoints: Objective response (OR) characterized by conventional radiological and functional imaging procedures and biological tumour markers at an early point of treatment with epirubicin + docetaxel and effects of addition of bevacizumab as reflected by these procedures. Early functional and biological changes signalling pathological complete response (pCR). Secondary endpoints: Secondary endpoints: Morphological and biological changes of tumours exposed for cytotoxic and targeted treatment. Disease-free survival. Safety.
Evaluations:
Before start of treatment:
Tumour staging: Bone scan, chest X-ray and liver ultrasound or CT scan of chest and abdomen within four weeks before start of treatment. Physical examination, conventional radiology (ultrasound and mammography including pre-treatment localization with carbon suspension) and functional imaging procedure (MRI or PET-CT or Contrast-Enhanced Ultrasound (CEUS) or Scintigraphy with 99m-Tc-HMPAO (Ceretec)) within two weeks before start of treatment.
Blood samples (SNP, metabolomics, M-30 assay, TK/XPA-210 assay, angiogenesis markers, TIMP-1, tissue factor) and tumour biopsies (transcriptomics, proteomics, IHC-stroma, AMOT) are collected within two weeks before start of treatment.
During treatment:
Physical examination before start of each treatment. Imaging procedures: Mammography, ultrasound (compulsory) one week (5-9 days) after cycles 2, 4 and 6. MRI, PET-CT, Contrast-Enhanced Ultrasound (CEUS) applied according to availability at the participating sites, one week (5-9 days) after cycles 2 and 4.
Tumour markers: Blood samples (proteomics, metabolomics, M-30 assay, TK/XPA-210 assay, angiogenesis markers, TIMP-1, tissue factor) are collected 48 hours after cycles 1 thru 4. Tumour tissue (transcriptomics, proteomics, IHC-stroma, AMOT) is taken charge of by biopsy one week (5-9 days) after cycle 2 and from the tumour specimen in connection with surgery.
Totally, 150-200 patients with measurable/evaluable primary breast cancer are planned for inclusion within a period of two years time. For each imaging method, approximately 40-50 patients will be included. The study is designed to find early predictors of response by testing a set-up of several different molecular and imaging tools. In addition, for each method changes of patterns occurring during treatment will be compared to baseline findings and, in the case of functional imaging, standard imaging procedures.
All patients will be followed for five years after operation with regard to outcome and toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Epirubicin Docetaxel Bevacizumab | Experimental | Drug: Epirubicin, Drug: Docetaxel, Drug: BevacizumabEpirubicin and docetaxel i.v. infusion q 3 weeks for 2 cycles. * If complete response this treatment continues for 4 cycles, totally 6 cycles. * If partial response or stable disease, epirubicin and docetaxel and bevacizumab i.v. infusion q 3 weeks for 4 cycles. * If progressive disease after the first 2 cycles individualized treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent
- Female patients with breast cancer confirmed by histology.
- Tumour and blood samples according to APPENDIX I available.
- Age 18 years or older. Elderly patients in condition adequate for chemotherapy.
- Localized primary breast cancer including inflammatory breast cancer suitable for primary medical treatment and/or regional lymph node metastases including ipsilateral supraclavicular nodes with breast cancer diagnosis confirmed by histological examination with or without breast tumour lesions.
Key exclusion criteria (11 listed)
- Distant metastases, including node metastases in the contralateral breast region and in the mediastina.
- Other malignancy for the last two years except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix.
- HER2-amplification verified by FISH analysis.
- Pregnancy or lactation.
- Uncontrolled hypertension, heart, liver, kidney related or other medical or psychiatric disorders.
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 |
|---|---|---|
| Epirubicin75 mg/m2 i.v. infusion, 30 min, cycle day 1, cycles 1-6. | Drug | Epirubicin Docetaxel Bevacizumab |
| DocetaxelAlso: Taxotere75 mg/m2 i.v. infusion, 60 min, cycles day 1, cycle 1-6. | Drug | Epirubicin Docetaxel Bevacizumab |
| BevacizumabAlso: Avastin15 mg/kg, i.v. infusion, 90 min, cycle day 1, cycles 3-6 if PR or SD after cycle 2. | Drug | Epirubicin Docetaxel Bevacizumab |
Primary outcome
Evaluation of the sensitivity and of defined diagnostic and biological procedures to detect response/non-response to neoadjuvant treatment at an early point among patients with breast cancer.
Time frame: 6 weeks
5 secondary outcomes
Identification of tumour characteristics and treatment-related changes of tumour characteristics predictive of long-term prognosis.
Time frame: 5 years
Comparison between the standard evaluation procedures mammography, conventional ultrasound and clinical examination and functional imaging techniques and biological procedures with emphasis on detection of response at an early point of treatment.
Time frame: 6 weeks
Studies on the addition of bevacizumab with regard to further improvement of response in tumours with stable (SD) or partial response (PR) and the impact of treatment on angiogenesis and local features of the tumour environment.
Time frame: 6 weeks
Acute toxicity
Time frame: 6 weeks after last chemotherapy
Late toxicity
Time frame: 5 years after last chemotherapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2016.
- Results publication: PubMed 27461224Saracco A, Szabo BK, Tanczos E, Bergh J, Hatschek T. Contrast-enhanced ultrasound (CEUS) in assessing early response among patients with invasive breast cancer undergoing neoadjuvant chemotherapy. Acta Radiol. 2017 Apr;58(4):394-402. doi: 10.1177/0284185116658322. Epub 2016 Jul 28.
- Derived from this study: PubMed 32423477Tribukait B. Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume. BMC Cancer. 2020 May 18;20(1):440. doi: 10.1186/s12885-020-06925-y.
- Derived from this study: PubMed 29078273Nakamura M, Zhang Y, Yang Y, Sonmez C, Zheng W, Huang G, Seki T, Iwamoto H, Ding B, Yin L, Foukakis T, Hatschek T, Li X, Hosaka K, Li J, Yu G, Wang X, Liu Y, Cao Y. Off-tumor targets compromise antiangiogenic drug sensitivity by inducing kidney erythropoietin production. Proc Natl Acad Sci U S A. 2017 Nov 7;114(45):E9635-E9644. doi: 10.1073/pnas.1703431114. Epub 2017 Oct 23.
- Swedish website of the study. Password requiredLink provided by the sponsor.
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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.
Thomas Hatschek, MD, PhD principal investigator
Karolinska University Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epirubicin, Docetaxel and Bevacizumab in people with Breast Cancer, run by Thomas Hatschek at 6 sites in Sweden.
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 8 inclusion and 11 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 8 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Sweden. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
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?
Evaluation of the sensitivity and of defined diagnostic and biological procedures to detect response/non-response to neoadjuvant treatment at an early point among patients with breast cancer. (time frame: 6 weeks). 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 NCT00957125, 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 Sep 2016.