Malignant Neoplasm of Female BreastPhase 2NCT01869192
Phase II Trial for Large ER-Negative Breast Cancers
A Phase 2 study testing Epirubicin, Cyclophosphamide and Docetaxel in people with Malignant Neoplasm of Female Breast, run by University of Colorado, Denver at 1 site in United States.
Trial summary
A primary objective of this study is to evaluate the in vivo response of tumor to chemotherapy through gene microarray analysis. Neoadjuvant treatment allows the unique opportunity to observe the in vivo effects of cytotoxic therapy on gene expression in tumor tissue. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Malignant Neoplasm of Female Breast
- What is being tested?
- Epirubicin, Cyclophosphamide and Docetaxel
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Mar 2003to 21 Aug 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- The diagnosis of breast cancer can be made by fine-needle aspiration (FNA), core, or tru-cut biopsy. Biopsy must demonstrate invasive adenocarcinoma.
- Patients must have a life expectancy of at least 1 year, excluding their diagnosis of cancer.
- Patients must have a mass on clinical or radiological examination of >1 cm and must be confined to either the breast or to the breast and ipsilateral axilla. Multiple masses permitted, provided one of them is >1cm.
- Patients may enter prior to ER or Her2 status being known, however if Her2 is positive, then the patient is withdrawn from the treatment phase of the trial.
- Patients with palpable mass with distant metastasis and/or palpable supraclavicular lymphadenopathy allowed if definitive local treatment is judged to be necessary.
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- Patients may have inflammatory breast cancer.
- Prior to time of entry, patients must have had the following:
- history and physical exam
- blood tests
- chest imaging within the last 3 months (chest x-ray, CT scan, PET/CT)
- bilateral mammogram
- Ultrasound of tumor with placement of clip to localize tumor should it respond completely to chemotherapy is recommended
- Bone scan and MRI of the breast as clinically indicated.
- Patients with clinically palpable lymph nodes are recommended to have a FNA biopsy to document the lymph node status. Patients may undergo a sentinel node biopsy procedure prior to preoperative chemotherapy.
- At time of entry
- White blood cell count (WBC) > 3,000
- platelet count > 100,000
- bilirubin, serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate oxaloacetate transaminase (SGPT), alkaline phosphatase, and serum creatinine must all be < 1.2 x upper limit of normal (ULN)
- calculated creatinine clearance [Cockcroft-Gault] > 50 ml/min. normalized to a 1.73 m2 body surface area (BSA). Patients with benign hyperbilirubinemia are also excluded.
- Patients with bone pain are eligible for inclusion if bone scan and/or roentgenological exam fail to disclose metastatic disease, or if metastatic disease is found, definitive local treatment is to be performed.
- Patients with non-breast malignancies are eligible if they have not received prior chemotherapy, or extensive radiation therapy, and are free from disease for at least two years. Patients with squamous or basal carcinoma of the skin that has been effectively treated, carcinoma in situ of the cervix that has been treated by surgery only are eligible. Patients with prior or simultaneous lobular or ductal carcinoma in situ of the ipsilateral or contralateral breast are also eligible. Patients with bilateral breast cancer for which at least one of the breast cancers meet the eligibility requirements are also eligible.
- Has a negative serum or urine pregnancy test within 7 days prior to initiation of chemotherapy (female patients of childbearing potential).
Who cannot join
- Patients with Her2 positive breast cancer
- Pregnancy or breast feeding at the time of proposed randomization. Women of childbearing potential with either a positive or no pregnancy test at baseline. Woman of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients will agree to continue contraception for 30 days from the date of the last study drug administration.
- Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
- Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil.
- Prior therapy for this breast cancer.
- Prior chemotherapy for a different breast cancer. Patients who have received prior anthracycline therapy for any malignancy are not eligible.
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- Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient from being subjected to any of the treatment options or surgery or would prevent prolonged follow-up.
- Active cardiac disease that would preclude the use of epirubicin. This includes:
- Any documented myocardial infarction or unstable angina;
- Any history of documented congestive heart failure;
- Valvular disease with documented cardiac function compromise;
- Patients with cardiomegaly on chest X-ray, or ventricular hypertrophy on EKG, unless they demonstrate adequate left ventricular ejection fraction (LVEF) > 45% by MUltiple Gated Acquisition (MUGA) or echocardiogram.
- Patients with a cardiac arrhythmia are eligible, provided the arrhythmia is not associated with concomitant heart failure or cardiac dysfunction.
- History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
- Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
- Known, existing uncontrolled coagulopathy
- Unwillingness to give written informed consent.
- Unwillingness to participate or inability to comply with the protocol for the duration of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Cancer Center
Aurora, Colorado, 80045
About this study
Official title: Differential Gene Regulation During Neoadjuvant Therapy Trial of Epirubicin/Cyclophosphamide (EC) vs Docetaxel/Capecitabine (DX) Regimens in Patients With Large ER-positive and ER-negative Breast Cancers: A Randomized Phase II Trial.
A primary objective of this study is to evaluate the in vivo response of tumor to chemotherapy through gene microarray analysis. Neoadjuvant treatment allows the unique opportunity to observe the in vivo effects of cytotoxic therapy on gene expression in tumor tissue. The investigators plan to evaluate several different questions by comparing gene profiles in different phases of treatment in this study. These are outlined below.
Hypotheses
- Chemotherapy enriches for tumor cell populations that have enhanced resistance and survival mechanisms. These mechanisms will in part be identifiable through changes in gene expression profiles pre vs. post treatment.
- Use of two distinct chemotherapy selection pressures, for example a DNA-damaging regimen (epirubicin and cyclophosphamide) or a mitotic spindle/metabolic targeted regimen (docetaxel and capecitabine), will allow for the identification of a smaller set of genes associated to resistance and survival mechanisms of broad importance.
- Genes associated with enrichment for resistance and survival mechanisms will not be present in large amounts pretreatment in tumors destined for complete pathologic response.
Read the detailed description
The clinical outcomes of breast cancer treatment are remarkably similar regardless of the regimen used, even though the individual drugs may differ substantially in mechanisms of action. We are interested in identifying a set of genes that may be associated with breast cancer cell survival following selection by chemotherapy. We intend to use two different selection pressures (different chemotherapy regimens with different mechanisms of action) in order to focus on those genes that are regulated similarly in response to either regimen.
Neoadjuvant chemotherapy is in common use for locally advanced breast cancers. Although it does not yet appear to impart a survival advantage, it does enhance the likelihood of breast conserving surgery and also provides important prognostic information. Taxotere appears to add significantly to pathologic complete responses when added to doxorubicin and cyclophosphamide alone. The combination of capecitabine and docetaxel was superior to docetaxel alone in metastatic disease. Many investigators are interested in incorporating this regimen for the treatment of earlier stages of breast cancer.
- Conditions
- Malignant Neoplasm of Female Breast
- Being tested
- Epirubicin, Cyclophosphamide, Docetaxel, Capecitabine, Radiation Therapy
- Keywords
- Malignant, Neoplasm, Cancer, Female, Breast, Stage II, Stage III
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpirubicinDrug
Also called Ellence, Pharmorubicin PFS, Pharmorubicin RDF
Epirubicin 90 mg/m2 d1 q3w
CyclophosphamideDrug
Also called Cytoxan, Neosar, Cytoxan Lyophilized
Cyclophosphamide 600 mg/m2 d1 q3w
DocetaxelDrug
Also called Docefrez, Taxotere
Docetaxel 75 mg/m2 d1 q3w
CapecitabineDrug
Also called Xeloda
Capecitabine 1000 mg/m2/dose bid x 14d q3w
Radiation TherapyRadiation
Standard dosing, fields depending on clinical findings
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | Arm A: Epirubicin 90 mg/m2 day 1 IV and Cyclophosphamide 600 mg/m2 day 1 IV q 3 weeks for 4 cycles, then surgery, then Docetaxel 75 mg/m2 IV day 1 plus Capecitabine 1000 mg/m2/dose po bid x 14 days q 3 weeks for 4 cycles, then radiation therapy as indicated. Post surgical chemotherapy must be initiated within 35 days after completion of definitive surgical treatment Receives: Drug: Epirubicin; Drug: Cyclophosphamide; Radiation: Radiation Therapy |
| Arm B | Active comparator | Arm B: Docetaxel 75 mg/m2 IV day 1 plus Capecitabine 1000 mg/m2/dose po bid x 14 days q 3 weeks for 4 cycles, then surgery, then Epirubicin 90 mg/m2 day 1 IV and Cyclophosphamide 600 mg/m2 day 1 IV q 3 weeks for 4 cycles, then radiation therapy as indicated. Post surgical chemotherapy must be initiated within 35 days after completion of definitive surgical treatment Receives: Drug: Docetaxel; Drug: Capecitabine; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
To describe the overall response rate as measured by physical exam and MRI if indicated using the following definition: Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Up to 8 months
Secondary outcomes (1)
Pathological Response
Pathological response (pCR or microscopic only primary) in both primary and nodes using the Miller-Payne criteria for pathologic response.
Measured: Up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2013 (estimated)
- Study start5 Mar 2003
- Primary completion18 Dec 2009
- Study completion21 Aug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Neoplasm of Female BreastStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized sequence of therapy.
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anthony Elias, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01869192
- Sponsor's protocol ID
- 02-824.cc
- Status last verified
- Sep 2019
- First submitted
- 28 May 2013
- Last updated
- 24 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Differential Gene Regulation During Neoadjuvant Therapy Trial of Epirubicin/Cyclophosphamide (EC) vs Docetaxel/Capecitabine (DX) Regimens in Patients With Large ER-positive and ER-negative Breast Cancers: A Randomized Phase II Trial.
- ClinicalTrials.gov ID
- NCT01869192
- Acronym / sponsor ID
- 02-824.cc
- Conditions
- Malignant Neoplasm of Female Breast
- Keywords
- Malignant, Neoplasm, Cancer, Female, Breast, Stage II, Stage III
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 5 Mar 2003 (actual)
- Primary completion
- 18 Dec 2009 (actual)
- Study completion
- 21 Aug 2010 (actual)
- First posted
- 5 Jun 2013 (estimated)
- Results
- Posted 19 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A primary objective of this study is to evaluate the in vivo response of tumor to chemotherapy through gene microarray analysis. Neoadjuvant treatment allows the unique opportunity to observe the in vivo effects of cytotoxic therapy on gene expression in tumor tissue. The investigators plan to evaluate several different questions by comparing gene profiles in different phases of treatment in this study. These are outlined below.
Hypotheses
- Chemotherapy enriches for tumor cell populations that have enhanced resistance and survival mechanisms. These mechanisms will in part be identifiable through changes in gene expression profiles pre vs. post treatment.
- Use of two distinct chemotherapy selection pressures, for example a DNA-damaging regimen (epirubicin and cyclophosphamide) or a mitotic spindle/metabolic targeted regimen (docetaxel and capecitabine), will allow for the identification of a smaller set of genes associated to resistance and survival mechanisms of broad importance.
- Genes associated with enrichment for resistance and survival mechanisms will not be present in large amounts pretreatment in tumors destined for complete pathologic response.
Detailed description
The clinical outcomes of breast cancer treatment are remarkably similar regardless of the regimen used, even though the individual drugs may differ substantially in mechanisms of action. We are interested in identifying a set of genes that may be associated with breast cancer cell survival following selection by chemotherapy. We intend to use two different selection pressures (different chemotherapy regimens with different mechanisms of action) in order to focus on those genes that are regulated similarly in response to either regimen.
Neoadjuvant chemotherapy is in common use for locally advanced breast cancers. Although it does not yet appear to impart a survival advantage, it does enhance the likelihood of breast conserving surgery and also provides important prognostic information. Taxotere appears to add significantly to pathologic complete responses when added to doxorubicin and cyclophosphamide alone. The combination of capecitabine and docetaxel was superior to docetaxel alone in metastatic disease. Many investigators are interested in incorporating this regimen for the treatment of earlier stages of breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized sequence of therapy.
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Epirubicin, Drug: Cyclophosphamide, Radiation: Radiation TherapyArm A: Epirubicin 90 mg/m2 day 1 IV and Cyclophosphamide 600 mg/m2 day 1 IV q 3 weeks for 4 cycles, then surgery, then Docetaxel 75 mg/m2 IV day 1 plus Capecitabine 1000 mg/m2/dose po bid x 14 days q 3 weeks for 4 cycles, then radiation therapy as indicated. Post surgical chemotherapy must be initiated within 35 days after completion of definitive surgical treatment |
| Arm B | Active comparator | Drug: Docetaxel, Drug: Capecitabine, Radiation: Radiation TherapyArm B: Docetaxel 75 mg/m2 IV day 1 plus Capecitabine 1000 mg/m2/dose po bid x 14 days q 3 weeks for 4 cycles, then surgery, then Epirubicin 90 mg/m2 day 1 IV and Cyclophosphamide 600 mg/m2 day 1 IV q 3 weeks for 4 cycles, then radiation therapy as indicated. Post surgical chemotherapy must be initiated within 35 days after completion of definitive surgical treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Written informed consent
- The diagnosis of breast cancer can be made by fine-needle aspiration (FNA), core, or tru-cut biopsy. Biopsy must demonstrate invasive adenocarcinoma.
- Patients must have a life expectancy of at least 1 year, excluding their diagnosis of cancer.
- Patients must have a mass on clinical or radiological examination of >1 cm and must be confined to either the breast or to the breast and ipsilateral axilla. Multiple masses permitted, provided one of them is >1cm.
- Patients may enter prior to ER or Her2 status being known, however if Her2 is positive, then the patient is withdrawn from the treatment phase of the trial.
Key exclusion criteria (18 listed)
- Patients with Her2 positive breast cancer
- Pregnancy or breast feeding at the time of proposed randomization. Women of childbearing potential with either a positive or no pregnancy test at baseline. Woman of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients will agree to continue contraception for 30 days from the date of the last study drug administration.
- Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
- Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil.
- Prior therapy for this breast cancer.
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 |
|---|---|---|
| EpirubicinAlso: Ellence, Pharmorubicin PFS, Pharmorubicin RDFEpirubicin 90 mg/m2 d1 q3w | Drug | Arm A |
| CyclophosphamideAlso: Cytoxan, Neosar, Cytoxan LyophilizedCyclophosphamide 600 mg/m2 d1 q3w | Drug | Arm A |
| DocetaxelAlso: Docefrez, TaxotereDocetaxel 75 mg/m2 d1 q3w | Drug | Arm B |
| CapecitabineAlso: XelodaCapecitabine 1000 mg/m2/dose bid x 14d q3w | Drug | Arm B |
| Radiation TherapyStandard dosing, fields depending on clinical findings | Radiation | Arm A, Arm B |
Primary outcome
Overall Response Rate
Time frame: Up to 8 months
To describe the overall response rate as measured by physical exam and MRI if indicated using the following definition: Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
1 secondary outcome
Pathological Response
Time frame: Up to 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Anthony Elias, MD principal investigator
University of Colorado, Denver
1 site 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, Cyclophosphamide and Docetaxel in people with Malignant Neoplasm of Female Breast, run by University of Colorado, Denver 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 23 inclusion and 18 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 24 Sep 2019. 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.
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?
Yes. Results are posted in the registry (first posted 19 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (time frame: Up to 8 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 24 Sep 2019.