Breast CancerPhase 2NCT00129376
Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel as Neoadjuvant Treatment of Breast Cancer Patients
A Phase 2 study testing Doxorubicin, Cyclophosphamide and Docetaxel in people with Breast Cancer, run by Spanish Breast Cancer Research Group at 6 sites in Spain.
Trial summary
Treatment consists of 4 AC cycles followed by 2 weekly docetaxel cycles (12 infusions). The pathological complete response rate obtained in previous studies is around 12%. The expected pathological complete response rate in this study is 25%. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Doxorubicin, Cyclophosphamide and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 6 sitesSpain
- Study dates
- Feb 2003to Feb 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 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent.
- Patients with breast cancer stages II and IIIA, with histological diagnoses as per true-cut or open biopsy.
- Negative extension study, including bilateral mammography, thoracic x-ray, computed tomography (CT)-scan or abdominal echography and bone scintigraphy.
- Analysis of hormone receptor status in primary tumour. It is highly recommended to obtain a tumour tissue sample before start of treatment, and after definitive surgery. These samples will be analysed centrally by Spanish Breast Cancer Research Group (GEICAM).
- Age >= 18 and <= 70 years old.
- Performance status as per Karnofsky index >= 80.
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- Minimum life expectancy of 6 months.
- Electrocardiogram (EKG) 12 weeks before registration to the study. If abnormalities are suspected, cardiac function must be assessed by left ventricular ejection fraction (LVEF).
- Haematology: neutrophils >= 2.0 x10^9/l; platelets >= 100 x10^9/l; hemoglobin >=10 g/dl.
- Hepatic function: total bilirubin <= 1 x upper normal limit (UNL); Aspartate aminotransferase (AST) (SGOT) and and Alanine aminotransferase (ALT) (SGPT) <= 2.5 x UNL; alkaline phosphatase <= 5 x UNL.
- Renal function: creatinine <= 1.5 x UNL; creatinine clearance >= 60 ml/min.
- Patients able to comply with study requirements.
- Negative pregnancy test.
- Adequate contraceptive method during the study and up to 3 months after definitive surgery.
Who cannot join
- Previous systemic therapy for breast cancer treatment.
- Previous treatments with anthracyclines or taxanes for any malignancy.
- Previous radiotherapy for breast cancer.
- Bilateral invasive breast cancer.
- Pregnant or lactating women.
- Previous motor or sensorial neurotoxicity grade >=2.
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- Other serious pathologies: congestive heart failure or angina pectoris; history of myocardial infarction in the previous year; uncontrolled hypertension (HT) or high risk arrhythmias.
- History of neurological or psychiatric impairment, precluding patients from providing free informed consent.
- Active infection.
- Active peptic ulcer; unstable diabetes mellitus.
- History of previous or current malignancies other than breast cancer, except for basal skin carcinoma, cervical in situ carcinoma, other tumour diagnosed and treated more than 10 years before, ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
- Chronic treatment with corticoids unless the treatment started > 6 months before registration to the study, and low doses are administered.
- Substitutive hormonal therapy. This treatment must be interrupted before inclusion in the study.
- Concomitant treatment with other investigational products or administration in the 30 previous days.
- Males.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Spain6 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, 15006
Hospital General Universitario de Alicante
Alicante, 03010
Hospital de la Ribera
Alzira, Valencia, 46600
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona, 08916
Fundación Jiménez Díaz
Madrid, 28040
Corporació Sanitaria Parc Taulí
Sabadell, Barcelona, 08208
About this study
Official title: Multicenter Phase II Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel (T) as Neoadjuvant Treatment for Operable Stage II and IIIA Breast Cancer Patients
Treatment consists of 4 AC cycles followed by 2 weekly docetaxel cycles (12 infusions).
The pathological complete response rate obtained in previous studies is around 12%. The expected pathological complete response rate in this study is 25%. With an alpha error of 0.05 and a beta error of 0.2, and following Simon´s 2 phase test, 19 patients are needed initially. With 2 pathological complete responses, patient recruitment will continue until approximately 61 patients are recruited. Twelve pathological complete responses are needed to confirm the study hypothesis.
Read the detailed description
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176). Adjuvant chemotherapy and radiotherapy were delivered according to the protocol of each participating center. Hormonal treatment was started after the last chemotherapy infusion in all patients with positive estrogen and/or progesterone receptor tumors and was continued for five years.
Semiquantitative determination of three molecular markers was carried out by immunocytochemical methods. Tissue samples were taken prior to initiation of chemotherapy from the core of the primary tumors. Specimens were sent to a central laboratory for analysis of Topo II, survivin and p27.
- Conditions
- Breast Cancer
- Being tested
- Doxorubicin, Cyclophosphamide, Docetaxel
- Keywords
- Stage II and IIIA breast Cancer., Neoadjuvant chemotherapy., Weekly docetaxel.
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
Also called adriamycin
CyclophosphamideDrug
Also called Cytoxan
DocetaxelDrug
Also called Taxotere
| Study group | Role | What they receive |
|---|---|---|
| Doxorubicin+cyclophosphamide - Docetaxel | Experimental | Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles. Later, docetaxel (36 mg/m2) was administered an intravenous infusion, weekly for six weeks followed by a 2-week resting period (8-week cycle). Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR) Rate
Pathological complete response was defined by the Miller \& Payne criteria. pCR was defined as no invasive cells identifiable in breast sections at surgery. Response was measured by physical exam and breast imaging before surgery and was evaluated according to the World Health Organization (WHO) criteria. Pathological response after surgery, was based on the proportion of remaining tumor and postchemotherapy changes, evaluating separately the response in the breast and in the axilla lymph nodes.
Measured: Up to 29 weeks
Secondary outcomes (4)
Clinical Response Rate (CRR)
CRR measured according to the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions, where:
- Complete Response (CR): disappearance of all target lesions
- Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions
- Progresive Disease (PD): >=20% increase from smallest sum of longest diameter recorded since treatment started (best response).
- Stable Disease (SD): Neither PD nor PR
Measured: Up to 29 weeks
Number of Participants With Over-expression of Topo II (>10% Cells With Nuclear Staining)
Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Over-expression of Topo II was defined as >10% cells with nuclear staining.
Measured: Up to 29 weeks
Number of Participants With Over-expression of Survivin (>1% Cells With Nuclear Staining)
Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Tumors with more than 1% of cells with nuclear staining were considered to be over-expressing this protein.
Measured: Up to 29 weeks
Number of Participants With Over-expression of p27 (>75% Cells With Nuclear Staining)
Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Sections were rated according to the percentage of tumor cells nuclei with positive staining (1 = < 25%; 2 = between 25-75% and 3 = > 75%).
Measured: Up to 29 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2005 (estimated)
- Study startFeb 2003
- Primary completionJul 2005
- Study completionFeb 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 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
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spanish Breast Cancer Research Group
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Instituto de Investigación Sanitaria de la Fundación Jiménez DíazStudy Director, Study director, Hospital Universitario Marqués de Valdecilla
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00129376
- Sponsor's protocol ID
- GEICAM 2002-03
- Status last verified
- Apr 2019
- First submitted
- 10 Aug 2005
- Last updated
- 5 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase II Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel (T) as Neoadjuvant Treatment for Operable Stage II and IIIA Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT00129376
- Acronym / sponsor ID
- GEICAM 2002-03
- Conditions
- Breast Cancer
- Keywords
- Stage II and IIIA breast Cancer., Neoadjuvant chemotherapy., Weekly docetaxel.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Spanish Breast Cancer Research GroupUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- Feb 2003 (actual)
- Primary completion
- Jul 2005 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 11 Aug 2005 (estimated)
- Results
- Posted 5 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment consists of 4 AC cycles followed by 2 weekly docetaxel cycles (12 infusions).
The pathological complete response rate obtained in previous studies is around 12%. The expected pathological complete response rate in this study is 25%. With an alpha error of 0.05 and a beta error of 0.2, and following Simon´s 2 phase test, 19 patients are needed initially. With 2 pathological complete responses, patient recruitment will continue until approximately 61 patients are recruited. Twelve pathological complete responses are needed to confirm the study hypothesis.
Detailed description
Patients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles (days 1, 22, 43 and 64). Three weeks later, docetaxel (36 mg/m2) was administered as a 30-min intravenous infusion, weekly for six weeks (days 85, 92, 99, 106, 113 and 120) followed by a 2-week resting period (8-week cycle). After that, patients received a second docetaxel cycle (infusions on days 141, 148, 155, 162, 169 and 176). Adjuvant chemotherapy and radiotherapy were delivered according to the protocol of each participating center. Hormonal treatment was started after the last chemotherapy infusion in all patients with positive estrogen and/or progesterone receptor tumors and was continued for five years.
Semiquantitative determination of three molecular markers was carried out by immunocytochemical methods. Tissue samples were taken prior to initiation of chemotherapy from the core of the primary tumors. Specimens were sent to a central laboratory for analysis of Topo II, survivin and p27.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Doxorubicin+cyclophosphamide - Docetaxel | Experimental | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: DocetaxelPatients received doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), both in a short intravenous infusion, every three weeks for four cycles. Later, docetaxel (36 mg/m2) was administered an intravenous infusion, weekly for six weeks followed by a 2-week resting period (8-week cycle). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Written informed consent.
- Patients with breast cancer stages II and IIIA, with histological diagnoses as per true-cut or open biopsy.
- Negative extension study, including bilateral mammography, thoracic x-ray, computed tomography (CT)-scan or abdominal echography and bone scintigraphy.
- Analysis of hormone receptor status in primary tumour. It is highly recommended to obtain a tumour tissue sample before start of treatment, and after definitive surgery. These samples will be analysed centrally by Spanish Breast Cancer Research Group (GEICAM).
- Age >= 18 and <= 70 years old.
Key exclusion criteria (15 listed)
- Previous systemic therapy for breast cancer treatment.
- Previous treatments with anthracyclines or taxanes for any malignancy.
- Previous radiotherapy for breast cancer.
- Bilateral invasive breast cancer.
- Pregnant or lactating women.
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 |
|---|---|---|
| DoxorubicinAlso: adriamycin | Drug | Doxorubicin+cyclophosphamide - Docetaxel |
| CyclophosphamideAlso: Cytoxan | Drug | Doxorubicin+cyclophosphamide - Docetaxel |
| DocetaxelAlso: Taxotere | Drug | Doxorubicin+cyclophosphamide - Docetaxel |
Primary outcome
Pathological Complete Response (pCR) Rate
Time frame: Up to 29 weeks
Pathological complete response was defined by the Miller \& Payne criteria. pCR was defined as no invasive cells identifiable in breast sections at surgery. Response was measured by physical exam and breast imaging before surgery and was evaluated according to the World Health Organization (WHO) criteria. Pathological response after surgery, was based on the proportion of remaining tumor and postchemotherapy changes, evaluating separately the response in the breast and in the axilla lymph nodes.
4 secondary outcomes
Clinical Response Rate (CRR)
Time frame: Up to 29 weeks
Number of Participants With Over-expression of Topo II (>10% Cells With Nuclear Staining)
Time frame: Up to 29 weeks
Number of Participants With Over-expression of Survivin (>1% Cells With Nuclear Staining)
Time frame: Up to 29 weeks
Number of Participants With Over-expression of p27 (>75% Cells With Nuclear Staining)
Time frame: Up to 29 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Click here for more information about this study: GEICAM 2002-03Link 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.
Study Director study director
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Study Director study director
Hospital Universitario Marqués de Valdecilla
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 Doxorubicin, Cyclophosphamide and Docetaxel in people with Breast Cancer, run by Spanish Breast Cancer Research Group at 6 sites in Spain.
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 15 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 5 Jul 2019. 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 Spain. 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 5 Jul 2019). 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 Complete Response (pCR) Rate (time frame: Up to 29 weeks). 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 5 Jul 2019.