Study of Neoadjuvant Docetaxel and Cyclophosphamide in Locally Advanced or Node Positive Primary Breast Cancer With Companion Pharmacokinetic and Pharmacogenomic Analyses

NCT01540110 | Completed Phase 2 DMC

• 1 other identifier: NCC0907
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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. 1.Pharmacokinetics (PK) and pharmacogenomics (PG) of docetaxel cyclophosphamide in Asian patients,
2. 2.Safety and toxicity of docetaxel cyclophosphamide in Asian patients, and
3. 3.To determine efficacy of short course (3 days) filgrastim in primary and secondary prophylaxis against febrile neutropenia in patients receiving docetaxel and cyclophosphamide.

Conditions

Breast Cancer

Keywords

Locally Advanced or Node Positive Primary Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  2 years

Study Arms (1)

Docetaxel + cyclophosphamide

EXPERIMENTAL

Drug: Neoadjuvant Docetaxel and Cyclophosphamide

Interventions

Neoadjuvant Docetaxel and Cyclophosphamide DRUG

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)

Docetaxel + cyclophosphamide

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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
• 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.
• 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.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Rebecca Dent, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: February 28, 2012
• Study Start: August 11, 2010
• Primary Completion: October 20, 2015
• Study Completion: October 20, 2015
• Last Updated: September 14, 2018

Record last verified: 2018-09

Locations

SG (1)