Breast CancerPhase 2NCT01540110
Study of Neoadjuvant Docetaxel and Cyclophosphamide in Locally Advanced or Node Positive Primary Breast Cancer With Companion Pharmacokinetic and Pharmacogenomic Analyses
A Phase 2 study testing Neoadjuvant Docetaxel and Cyclophosphamide in people with Breast Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
Primary The purpose of this study is to evaluate tumour pathological complete response rate after six cycles of neoadjuvant docetaxel and cyclophosphamide in an Asian population. Secondary To assess: 1. Pharmacokinetics (PK) and pharmacogenomics (PG) of docetaxel cyclophosphamide in Asian patients, 2. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Neoadjuvant Docetaxel and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteSingapore
- Study dates
- 11 Aug 2010to 20 Oct 2015
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed invasive breast cancer.
- Patients must have either locally advanced (cT3-T4, N0-3 or cTx, T0-4, N2-N3) or lymph node positive breast cancer
- Age >21 years. Because no dosing or adverse event data are currently available on the use of docetaxel in patients <21 years of age, children are excluded from this study but will be eligible for future pediatric phase 2 combination trials.
- Life expectancy of greater than 10 years.
- ECOG performance status <2 (Karnofsky >60%; see Appendix A).
- Patients must have normal organ and marrow function as defined below:
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- leukocytes >3,000/mL
- absolute neutrophil count >1,500/mL
- platelets >100,000/mL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
- creatinine within normal institutional limits OR
- creatinine clearance >40 mL/min for patients if creatinine levels above institutional normal
- The effects of docetaxel on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
- Both men and women of all races and ethnic groups are eligible for this trial.
- Protocol precautions and restrictions
- Patients who are pregnant or actively breast feeding are not eligible to participate in this study as stated in 3.2.8. Female patients of child bearing potential will be required to use reliable methods of contraception for the duration of the study and until 4 weeks after the last dose of study treatment.
Who cannot join
- HER2 positive breast cancer
- Metastatic breast cancer
- Patients who have had any chemotherapy or radiotherapy prior to entering the study.
- Patients receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel, cyclophosphamide, lenograstim or filgrastim.
- History of pre-existing peripheral neuropathy
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because chemotherapy in general including docetaxel and cyclophosphamide used in this study are pregnancy class D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother is treated with chemotherapy. These potential risks may also apply to other agents used in this study.
- Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with chemotherapy or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
- Patients with prior malignancies are excluded except for basal cell carcinoma of the skin and carcinoma in-situ of the cervix who have received curative treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Study of Neoadjuvant Docetaxel and Cyclophosphamide in Locally Advanced or Node Positive Primary Breast Cancer With Companion Pharmacokinetic and Pharmacogenomic Analyses
Primary
The purpose of this study is to evaluate tumour pathological complete response rate after six cycles of neoadjuvant docetaxel and cyclophosphamide in an Asian population.
Secondary
To assess:
- Pharmacokinetics (PK) and pharmacogenomics (PG) of docetaxel cyclophosphamide in Asian patients,
- Safety and toxicity of docetaxel cyclophosphamide in Asian patients, and
- To determine efficacy of short course (3 days) filgrastim in primary and secondary prophylaxis against febrile neutropenia in patients receiving docetaxel and cyclophosphamide.
Read the detailed description
Study Design and Duration
Simon Optimal two-stage Phase II design will be used for this trial. With a null hypothesis of p0=5% and an alternative hypothesis of p1=20%, significance level, α=5% and power, (1-β)=90%, a total of 41 patients will be required, with 21 patients to be recruited for the first stage.
Hence, 21 to 41 patients will be recruited at National Cancer Centre Singapore over 36 months
Patient Sample
Patients with newly diagnosed, histological confirmed HER-2 negative clinically node positive or locally advanced (cT3-T4, N0-3 or cTx, T0-4, N2-N3) primary breast cancer without evidence of metastatic disease.
Dosage/ Dosage Form, Route and Dose Regimen
Node Positive or Locally Advanced HER2 Negative Breast Cancer proceed to Docetaxel 75 mg/m2 + Cyclophosphamide 600 mg/m2 q21 days x 6 proceed to surgery
NOTE: cyclophosphamide is administered by intravenous infusion over 10 minutes followed by docetaxel over 90 minutes Patients will receive further chemotherapy, radiotherapy, endocrine therapy and targeted therapy as per institutional guidelines after surgery.
Patients with clinical non-response after 4 cycles of docetaxel and cyclophosphamide are most unlikely to have a pathological complete response. Hence, discontinuation of study and cross over to an anthracycline based chemotherapy is allowed at that point at the discretion of the treating oncologist. These patients will be classified as pathological non complete response.
Patients with progressive disease at any time will discontinue study treatment and receive salvage therapy.
Efficacy Measurements
Pathological response will be assessed by evaluation of resected surgical specimen after completion of protocol treatment.
Safety Measurements
Vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, adverse events (AEs), serial laboratory safety tests. Proportion of patients with febrile neutropenia despite primary prophylactic G-CSF will be reviewed when 6,12 ,18, 24 and 30 patients have been accrued. Increase in number of doses of primary prophylactic G-CSF will be implemented if the lower limit of the 95% confidence interval of proportion exceeds 20%.
Data Analysis
All patients who have received at least 1 dose of study treatment will be included in the safety and efficacy analyses.
Pharmacokinetic (PK), Pharmacogenetic (PG) and Correlative Studies
Consent will be obtained for future analysis of any stored preoperative tumour biopsy specimens for possible gene expression profiles predictive of docetaxel and cyclophosphamide. Patients will undergo blood sampling for docetaxel and cyclophosphamide PK studies on cycle 1 day 1 (see page 22 for detailed timing). Whole blood will be collected at baseline for genotyping for CYP3A4, CYP3A5, CYP2B6, CYP2C19, ALDH, GST, ABCB1, SLCO1B3, PXR, CAR, HNF4α genes
ALL PATIENTS WITH SERIOUS ADVERSE EVENTS MUST BE FOLLOWED UP FOR OUTCOME.
- Conditions
- Breast Cancer
- Being tested
- Neoadjuvant Docetaxel and Cyclophosphamide
- Keywords
- Locally Advanced or Node Positive Primary Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant Docetaxel and CyclophosphamideDrug
5.1.1 Docetaxel Docetaxel at a dose of 75 mg/m2 will be administered by intravenous infusion over 90 minutes (AFTER completion of cyclosphosphamide 600 mg/m2) on D1 every 21 days for 6 cycles using nonpolyvinylchloride tubing.
Standard premedication with oral dexamethasone 8 mg bd on D-1, D1 and D2 will be administered. Alternatively, intravenous dexamethasone 8 mg before docetaxel followed by oral dexamethasone 8 mg bd on D1 and D2 can be given.
Routine prevention of chemotherapy induced emesis will be administered (see 5.2.2)
5.1.2 Cyclophosphamide
Cyclophosphamide 600 mg/m2 by slow intravenous infusion over 10 minutes (BEFORE docetaxel) will be administered every 21 days for 6 cycles.
No premedications are required except for routine prevention of chemotherapy induced emesis (see 5.2.2)
| Study group | Role | What they receive |
|---|---|---|
| Docetaxel + cyclophosphamide | Experimental | Not described Receives: Drug: Neoadjuvant Docetaxel and Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate tumour pathological complete response rate after 6 cycles of neoadjuvant docetaxel and cyclophosphamide in Asian population
To evaluate tumour pathological complete response rate after 6 cycles of neoadjuvant docetaxel and cyclophosphamide in Asian population
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2012 (estimated)
- Study start11 Aug 2010
- Primary completion20 Oct 2015
- Study completion20 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rebecca Dent, MD, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01540110
- Sponsor's protocol ID
- NCC0907
- Status last verified
- Sep 2018
- First submitted
- 31 Jan 2012
- Last updated
- 14 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Neoadjuvant Docetaxel and Cyclophosphamide in Locally Advanced or Node Positive Primary Breast Cancer With Companion Pharmacokinetic and Pharmacogenomic Analyses
- ClinicalTrials.gov ID
- NCT01540110
- Acronym / sponsor ID
- NCC0907
- Conditions
- Breast Cancer
- Keywords
- Locally Advanced or Node Positive Primary Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- 11 Aug 2010
- Primary completion
- 20 Oct 2015 (actual)
- Study completion
- 20 Oct 2015 (actual)
- First posted
- 28 Feb 2012 (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.
Primary
The purpose of this study is to evaluate tumour pathological complete response rate after six cycles of neoadjuvant docetaxel and cyclophosphamide in an Asian population.
Secondary
To assess:
- Pharmacokinetics (PK) and pharmacogenomics (PG) of docetaxel cyclophosphamide in Asian patients,
- Safety and toxicity of docetaxel cyclophosphamide in Asian patients, and
- To determine efficacy of short course (3 days) filgrastim in primary and secondary prophylaxis against febrile neutropenia in patients receiving docetaxel and cyclophosphamide.
Detailed description
Study Design and Duration
Simon Optimal two-stage Phase II design will be used for this trial. With a null hypothesis of p0=5% and an alternative hypothesis of p1=20%, significance level, α=5% and power, (1-β)=90%, a total of 41 patients will be required, with 21 patients to be recruited for the first stage.
Hence, 21 to 41 patients will be recruited at National Cancer Centre Singapore over 36 months
Patient Sample
Patients with newly diagnosed, histological confirmed HER-2 negative clinically node positive or locally advanced (cT3-T4, N0-3 or cTx, T0-4, N2-N3) primary breast cancer without evidence of metastatic disease.
Dosage/ Dosage Form, Route and Dose Regimen
Node Positive or Locally Advanced HER2 Negative Breast Cancer proceed to Docetaxel 75 mg/m2 + Cyclophosphamide 600 mg/m2 q21 days x 6 proceed to surgery
NOTE: cyclophosphamide is administered by intravenous infusion over 10 minutes followed by docetaxel over 90 minutes Patients will receive further chemotherapy, radiotherapy, endocrine therapy and targeted therapy as per institutional guidelines after surgery.
Patients with clinical non-response after 4 cycles of docetaxel and cyclophosphamide are most unlikely to have a pathological complete response. Hence, discontinuation of study and cross over to an anthracycline based chemotherapy is allowed at that point at the discretion of the treating oncologist. These patients will be classified as pathological non complete response.
Patients with progressive disease at any time will discontinue study treatment and receive salvage therapy.
Efficacy Measurements
Pathological response will be assessed by evaluation of resected surgical specimen after completion of protocol treatment.
Safety Measurements
Vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, adverse events (AEs), serial laboratory safety tests. Proportion of patients with febrile neutropenia despite primary prophylactic G-CSF will be reviewed when 6,12 ,18, 24 and 30 patients have been accrued. Increase in number of doses of primary prophylactic G-CSF will be implemented if the lower limit of the 95% confidence interval of proportion exceeds 20%.
Data Analysis
All patients who have received at least 1 dose of study treatment will be included in the safety and efficacy analyses.
Pharmacokinetic (PK), Pharmacogenetic (PG) and Correlative Studies
Consent will be obtained for future analysis of any stored preoperative tumour biopsy specimens for possible gene expression profiles predictive of docetaxel and cyclophosphamide. Patients will undergo blood sampling for docetaxel and cyclophosphamide PK studies on cycle 1 day 1 (see page 22 for detailed timing). Whole blood will be collected at baseline for genotyping for CYP3A4, CYP3A5, CYP2B6, CYP2C19, ALDH, GST, ABCB1, SLCO1B3, PXR, CAR, HNF4α genes
ALL PATIENTS WITH SERIOUS ADVERSE EVENTS MUST BE FOLLOWED UP FOR OUTCOME.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Docetaxel + cyclophosphamide | Experimental | Drug: Neoadjuvant Docetaxel and Cyclophosphamide |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically confirmed invasive breast cancer.
- Patients must have either locally advanced (cT3-T4, N0-3 or cTx, T0-4, N2-N3) or lymph node positive breast cancer
- Age >21 years. Because no dosing or adverse event data are currently available on the use of docetaxel in patients <21 years of age, children are excluded from this study but will be eligible for future pediatric phase 2 combination trials.
- Life expectancy of greater than 10 years.
- ECOG performance status <2 (Karnofsky >60%; see Appendix A).
Key exclusion criteria (10 listed)
- HER2 positive breast cancer
- Metastatic breast cancer
- Patients who have had any chemotherapy or radiotherapy prior to entering the study.
- Patients receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel, cyclophosphamide, lenograstim or filgrastim.
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 |
|---|---|---|
| Neoadjuvant Docetaxel and Cyclophosphamide5.1.1 Docetaxel Docetaxel at a dose of 75 mg/m2 will be administered by intravenous infusion over 90 minutes (AFTER completion of cyclosphosphamide 600 mg/m2) on D1 every 21 days for 6 cycles using nonpolyvinylchloride tubing. Standard premedication with oral dexamethasone 8 mg bd on D-1, D1 and D2 will be administered. Alternatively, intravenous dexamethasone 8 mg before docetaxel followed by oral dexamethasone 8 mg bd on D1 and D2 can be given. Routine prevention of chemotherapy induced emesis will be administered (see 5.2.2) 5.1.2 Cyclophosphamide Cyclophosphamide 600 mg/m2 by slow intravenous infusion over 10 minutes (BEFORE docetaxel) will be administered every 21 days for 6 cycles. No premedications are required except for routine prevention of chemotherapy induced emesis (see 5.2.2) | Drug | Docetaxel + cyclophosphamide |
Primary outcome
To evaluate tumour pathological complete response rate after 6 cycles of neoadjuvant docetaxel and cyclophosphamide in Asian population
Time frame: 2 years
To evaluate tumour pathological complete response rate after 6 cycles of neoadjuvant docetaxel and cyclophosphamide in Asian population
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 14 Sep 2018.
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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.
Rebecca Dent, MD principal investigator
National Cancer Centre, Singapore
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 Neoadjuvant Docetaxel and Cyclophosphamide in people with Breast Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
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 14 Sep 2018. 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 Singapore. 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?
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?
To evaluate tumour pathological complete response rate after 6 cycles of neoadjuvant docetaxel and cyclophosphamide in Asian population (time frame: 2 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 14 Sep 2018.