Breast CancerPhase 2TACACNCT00206518
Taxotere and Adriamycin/Cytoxan (AC) Validation in Breast Cancer Patients
A Phase 2 study testing Taxotere/Docetaxel, Adriamycin/Cytoxan and doxorubicin in people with Breast Cancer, run by Mothaffar Rimawi at 1 site in United States.
Trial summary
The purpose of this study is to learn if the biomarker information obtained (learned or received) from the earlier studies can tell us whether or not Taxotere and/or Adriamycin/Cytoxan can cause tumors to become smaller. 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?
- Taxotere/Docetaxel, Adriamycin/Cytoxan and doxorubicin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 167 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2004to 10 Oct 2016
- 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
- All patients must be female.
- Signed informed consent.
- Primary breast cancers must be of clinical and/or radiologic size >3 cm, and deemed surgically operable.
- Negative serum pregnancy test (bHCG) within 7 days of starting study, if of child-bearing potential.
- Adequate bone marrow function:
- Hematocrit of greater than 30%,
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- total neutrophil count must be >1.5 x 10^9/L and
- platelets of > 100 x 10^9/L prior to the start of any cycle.
- Renal function tests:
- creatinine within 1.5 times of the institution's upper limit of normal (ULN).
- Liver function tests:
- Total serum bilirubin within ULN, and
- liver transaminases within 2.5 times ULN, and
- alkaline phosphatase within 5 times ULN.
- Electrocardiogram showing no acute ischemic changes.
- Performance status (World Health Organization [WHO] scale) <2.
- Age > 18 years.
- Patients older than 70 years of age should have left ventricular ejection fraction within ULN by multigated acquisition scan (MUGA) or 2D echocardiogram.
Who cannot join
- Patients with metastatic breast cancer.
- Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
- Women who are lactating or breastfeeding.
- Severe underlying chronic illness or disease.
- Peripheral neuropathy - grade 2 or greater.
- Patients on other investigational drugs while on study will be excluded.
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- Severe or uncontrolled hypertension, history of congestive heart failure, acute myocardial infarction, or severe coronary arterial disease.
- Prior taxane or anthracycline chemotherapy for malignancy.
- Patients with a history of severe hypersensitivity reaction to Taxotere or other drugs formulated with polysorbate 80.
- No previous or current malignancies at other sites within the last 5 years, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Multicenter Trial of Neoadjuvant Taxotere (T) and Adriamycin/Cytoxan (Ac): A Validation
The purpose of this study is to learn if the biomarker information obtained (learned or received) from the earlier studies can tell us whether or not Taxotere and/or Adriamycin/Cytoxan can cause tumors to become smaller.
Read the detailed description
Large clinical trials have confirmed the value of systemic adjuvant therapy in decreasing the risk of recurrence and death in patients with early breast cancer. However, the need to identify breast cancer patients who will benefit from adjuvant therapy, while sparing others from the side effects of futile treatment, is spurring research into predictive markers of chemotherapy sensitivity and resistance. In the adjuvant setting, extremely large trials and long follow-up would be required to prospectively validate the predictive value of biomarkers of chemotherapy sensitivity or resistance. In part this is because response is not directly observable. Preoperative chemotherapy for large tumors (>3cm) or inoperable breast cancer is well established and is the standard of care for locally advanced breast cancer. Data from large series of patients have demonstrated that preoperative (neoadjuvant) chemotherapy leads to significant reduction of tumor size (downstaging) and improves both the rate and the cosmetic results of breast- conserving surgery. The degree of response to neoadjuvant therapy has been shown to predict improved overall survival. This is therefore an attractive setting to study predictors of response because tissue is accessible from pre- therapeutic biopsies and tumor response is directly observable.
In an early proof-of-principle pilot study of single agent neoadjuvant docetaxol, we identified a predictive gene expression pattern, and, using leave-one-cross validation, a method of internal validation, we demonstrated that the pattern was likely to accurately discriminate between responders and non-responders (Chang, J.C., et al., Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet, 2003. 362(9381): p. 362-9). A similar pilot study of neoadjuvant AC undertaken by a collaborator in the UK suggests that different profiles will be predictive for AC response.
In order to definitively determine predictive patterns for both regimens (T and AC) using improved technology for RNA preparation and a larger, more comprehensive gene expression array, we undertook a randomized Phase II trial of these two widely used regimens (Protocol H-11624 - A RANDOMIZED MULTICENTER TRIAL OF NEOADJUVANT TAXOTERE AND ADRIAMYCIN/CYTOXAN (AC): A BIOLOGIC CORRELATIVE STUDY). The trial is nearing completion, having recruited more than 90 patients out of an expected 120 patients. To date, the risks associated with this study have been modest, and there have been no unexpected adverse events. The laboratory work is well underway and gives every indication that clinically useful classifiers to predict treatment efficacy will result.
- Conditions
- Breast Cancer
- Being tested
- Taxotere/Docetaxel, Adriamycin/Cytoxan, doxorubicin
- Keywords
- Breast, Cancer, Taxotere, AC, Validation, Neoadjuvant
- Medical subject headings
- Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Taxotere/DocetaxelDrug
Also called docetaxel
Taxotere
Adriamycin/CytoxanDrug
Also called doxorubicin
Adriamycin/Cytoxan
doxorubicinDrug
Also called AC, ADRIAMYCIN/CYTOXAN
AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles before surgery.
| Study group | Role | What they receive |
|---|---|---|
| A: Taxotere/Docetaxel | Experimental | Chemotherapy In Arm A, patients will receive single agent Taxotere (100 mg/m2) every 3 weeks for 4 cycles before surgery. Primary surgery will then be conducted, if operable, following completion of neoadjuvant treatment. This will be followed by standard adjuvant AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles. For patients whose BSA is greater than 2.0 m2, the Adriamycin dosage will be calculated using BSA = 2.0 m2. This is done in order to minimize Adriamycin-induced cardiotoxicity. Receives: Drug: Taxotere/Docetaxel; Drug: doxorubicin |
| B: AC Adriamycin/Cytoxan | Experimental | In Arm B, patients will receive AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles before surgery. For patients whose BSA is greater than 2.0 m2, the Adriamycin dosage will be calculated using BSA = 2.0 m2. Primary surgery will then be conducted, if operable, following completion of neoadjuvant treatment. This will be followed by 4 cycles of single agent Taxotere (100 mg/m2) every 3 weeks. Receives: Drug: Adriamycin/Cytoxan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Tumor Response to Neoadjuvant Chemotherapy (Taxotere and AC)
The patients' pathological response were assessed using Chevalier's system which graded the responses into Chevalier 1, 2, 3A, 3B, 3C, 3D, and 4, defined as:
- Disappearance of all tumor either on macroscopic or microscopic assessment in both the breast and LN (pCR)
- Presence of in situ carcinoma in the breast. No invasive tumor in breast and no tumor in LN (pCR)
- Presence of invasive cancer with stromal alteration such as sclerosis or fibrosis (pPR) 3A: Subjectively > 75% therapeutic effect 3B: Subjectively between 50% - 75% therapeutic effect 3C: Subjectively between 25% - 50% therapeutic effect 3D: Subjectively < 25% therapeutic effect OR Grade 4
- No or few modification of tumoral appearance (pNR).
Measured: 10 years
Secondary outcomes (2)
Disease Relapse
Data associated with relapse and progression will be obtained over the course of 10 years. Relapse/progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 10 years
Overall Survival
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startSep 2004
- Primary completionOct 2016
- Study completion10 Oct 2016
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 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mothaffar Rimawi
- Sponsor type
- University, hospital or other
- Collaborators
- Baylor College of Medicine
- Responsible party
- Sponsor-investigator, Mothaffar Rimawi, Baylor Breast Care Center
- Investigators
- Mothaffar Rimawi, MD, Principal investigator, Baylor Breast Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00206518
- Sponsor's protocol ID
- H 16039
- Acronym
- TACAC
- Status last verified
- Jul 2020
- First submitted
- 14 Sep 2005
- Last updated
- 28 Jul 2020
- 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 28 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Multicenter Trial of Neoadjuvant Taxotere (T) and Adriamycin/Cytoxan (Ac): A Validation
- ClinicalTrials.gov ID
- NCT00206518
- Acronym / sponsor ID
- TACAC / H 16039
- Conditions
- Breast Cancer
- Keywords
- Breast, Cancer, Taxotere, AC, Validation, Neoadjuvant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 167 participants (actual)
- Lead sponsor
- Mothaffar RimawiUniversity, hospital or other
- Collaborators
- Baylor College of Medicine
- Study start
- Sep 2004
- Primary completion
- Oct 2016 (actual)
- Study completion
- 10 Oct 2016 (actual)
- First posted
- 21 Sep 2005 (estimated)
- Results
- Posted 6 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn if the biomarker information obtained (learned or received) from the earlier studies can tell us whether or not Taxotere and/or Adriamycin/Cytoxan can cause tumors to become smaller.
Detailed description
Large clinical trials have confirmed the value of systemic adjuvant therapy in decreasing the risk of recurrence and death in patients with early breast cancer. However, the need to identify breast cancer patients who will benefit from adjuvant therapy, while sparing others from the side effects of futile treatment, is spurring research into predictive markers of chemotherapy sensitivity and resistance. In the adjuvant setting, extremely large trials and long follow-up would be required to prospectively validate the predictive value of biomarkers of chemotherapy sensitivity or resistance. In part this is because response is not directly observable. Preoperative chemotherapy for large tumors (>3cm) or inoperable breast cancer is well established and is the standard of care for locally advanced breast cancer. Data from large series of patients have demonstrated that preoperative (neoadjuvant) chemotherapy leads to significant reduction of tumor size (downstaging) and improves both the rate and the cosmetic results of breast- conserving surgery. The degree of response to neoadjuvant therapy has been shown to predict improved overall survival. This is therefore an attractive setting to study predictors of response because tissue is accessible from pre- therapeutic biopsies and tumor response is directly observable.
In an early proof-of-principle pilot study of single agent neoadjuvant docetaxol, we identified a predictive gene expression pattern, and, using leave-one-cross validation, a method of internal validation, we demonstrated that the pattern was likely to accurately discriminate between responders and non-responders (Chang, J.C., et al., Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet, 2003. 362(9381): p. 362-9). A similar pilot study of neoadjuvant AC undertaken by a collaborator in the UK suggests that different profiles will be predictive for AC response.
In order to definitively determine predictive patterns for both regimens (T and AC) using improved technology for RNA preparation and a larger, more comprehensive gene expression array, we undertook a randomized Phase II trial of these two widely used regimens (Protocol H-11624 - A RANDOMIZED MULTICENTER TRIAL OF NEOADJUVANT TAXOTERE AND ADRIAMYCIN/CYTOXAN (AC): A BIOLOGIC CORRELATIVE STUDY). The trial is nearing completion, having recruited more than 90 patients out of an expected 120 patients. To date, the risks associated with this study have been modest, and there have been no unexpected adverse events. The laboratory work is well underway and gives every indication that clinically useful classifiers to predict treatment efficacy will result.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: Taxotere/Docetaxel | Experimental | Drug: Taxotere/Docetaxel, Drug: doxorubicinChemotherapy In Arm A, patients will receive single agent Taxotere (100 mg/m2) every 3 weeks for 4 cycles before surgery. Primary surgery will then be conducted, if operable, following completion of neoadjuvant treatment. This will be followed by standard adjuvant AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles. For patients whose BSA is greater than 2.0 m2, the Adriamycin dosage will be calculated using BSA = 2.0 m2. This is done in order to minimize Adriamycin-induced cardiotoxicity. |
| B: AC Adriamycin/Cytoxan | Experimental | Drug: Adriamycin/CytoxanIn Arm B, patients will receive AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles before surgery. For patients whose BSA is greater than 2.0 m2, the Adriamycin dosage will be calculated using BSA = 2.0 m2. Primary surgery will then be conducted, if operable, following completion of neoadjuvant treatment. This will be followed by 4 cycles of single agent Taxotere (100 mg/m2) every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- All patients must be female.
- Signed informed consent.
- Primary breast cancers must be of clinical and/or radiologic size >3 cm, and deemed surgically operable.
- Negative serum pregnancy test (bHCG) within 7 days of starting study, if of child-bearing potential.
- Adequate bone marrow function:
Key exclusion criteria (10 listed)
- Patients with metastatic breast cancer.
- Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
- Women who are lactating or breastfeeding.
- Severe underlying chronic illness or disease.
- Peripheral neuropathy - grade 2 or greater.
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 |
|---|---|---|
| Taxotere/DocetaxelAlso: docetaxelTaxotere | Drug | A: Taxotere/Docetaxel |
| Adriamycin/CytoxanAlso: doxorubicinAdriamycin/Cytoxan | Drug | B: AC Adriamycin/Cytoxan |
| doxorubicinAlso: AC, ADRIAMYCIN/CYTOXANAC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, every 3 weeks) for 4 cycles before surgery. | Drug | A: Taxotere/Docetaxel |
Primary outcome
Pathological Tumor Response to Neoadjuvant Chemotherapy (Taxotere and AC)
Time frame: 10 years
The patients' pathological response were assessed using Chevalier's system which graded the responses into Chevalier 1, 2, 3A, 3B, 3C, 3D, and 4, defined as: 1. Disappearance of all tumor either on macroscopic or microscopic assessment in both the breast and LN (pCR) 2. Presence of in situ carcinoma in the breast. No invasive tumor in breast and no tumor in LN (pCR) 3. Presence of invasive cancer with stromal alteration such as sclerosis or fibrosis (pPR) 3A: Subjectively > 75% therapeutic effect 3B: Subjectively between 50% - 75% therapeutic effect 3C: Subjectively between 25% - 50% therapeutic effect 3D: Subjectively < 25% therapeutic effect OR Grade 4 4. No or few modification of tumoral appearance (pNR).
2 secondary outcomes
Disease Relapse
Time frame: 10 years
Overall Survival
Time frame: 10 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2020.
- 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.
Mothaffar Rimawi, MD principal investigator
Baylor Breast Center
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 Taxotere/Docetaxel, Adriamycin/Cytoxan and doxorubicin in people with Breast Cancer, run by Mothaffar Rimawi 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 18 inclusion and 10 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 28 Jul 2020. 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 6 Jun 2017). 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?
Pathological Tumor Response to Neoadjuvant Chemotherapy (Taxotere and AC) (time frame: 10 years). 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 28 Jul 2020.