Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments 5-fluorouracil, cyclophosphamide, docetaxel, epirubicin, herceptin iv, herceptin sc
Phase phase 3
Sponsor Hoffmann-La Roche
Start date October 2009
End date January 2017
Trial size 596 participants
Trial identifier NCT00950300, 2008-007326-19, BO22227

Summary

In this open-label multicenter trial, participants with operable or locally advanced breast cancer will be randomized to pre-operative treatment with 8 cycles of chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil, epirubicin, and cyclophosphamide) concurrent with either SC Herceptin or IV Herceptin. After surgery, participants will receive a further 10 cycles of SC or IV Herceptin as per randomization to complete 1 year of treatment. All cycles will be 21 days in length. After the end of study treatment, participants will be followed for safety and efficacy for up to 5 years or until disease recurrence, whichever is earlier.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Participants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.
5-fluorouracil
Participants will receive 5-fluorouracil, 500 milligrams per meter-squared (mg/m^2) via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.
cyclophosphamide
Participants will receive cyclophosphamide, 500 mg/m^2 via IV bolus, on Day 1 of every 21-day cycle during Cycles 5 to 8.
docetaxel
Participants will receive docetaxel, 75 mg/m^2 via IV infusion on Day 1 of every 21-day cycle during Cycles 1 to 4.
epirubicin
Participants will receive epirubicin, 75 mg/m^2 via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.
herceptin iv Trastuzumab
Herceptin will be administered as 8 mg/kg (loading dose during Cycle 1) and 6 mg/kg (subsequent cycles) via IV infusion on Day 1 of each 21-day cycle for a total of 18 cycles.
(Experimental)
Participants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.
5-fluorouracil
Participants will receive 5-fluorouracil, 500 milligrams per meter-squared (mg/m^2) via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.
cyclophosphamide
Participants will receive cyclophosphamide, 500 mg/m^2 via IV bolus, on Day 1 of every 21-day cycle during Cycles 5 to 8.
docetaxel
Participants will receive docetaxel, 75 mg/m^2 via IV infusion on Day 1 of every 21-day cycle during Cycles 1 to 4.
epirubicin
Participants will receive epirubicin, 75 mg/m^2 via IV bolus or infusion, on Day 1 of every 21-day cycle during Cycles 5 to 8.
herceptin sc Trastuzumab
Herceptin will be administered as fixed dose 600 mg SC on Day 1 of each 21-day cycle for a total of 18 cycles.

Primary Outcomes

Measure
Serum trough concentration (Ctrough) of Herceptin (observed pre-surgery)
time frame: Pre-dose (0 hours) on Day 1 of Cycles 1 to 8 (cycle length of 21 days)
Percentage of participants with pathological complete response (pCR) according to Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0)
time frame: After surgery between Cycles 8 and 9 (cycle length of 21 days)

Secondary Outcomes

Measure
Ctrough of Herceptin (observed post-surgery and predicted pre-surgery and post-surgery)
time frame: Pre-dose (0 hours) on Day 1 of Cycles 1 to 11, and 12; on Days 2 and 15 of Cycle 9; and on Days 2, 4, 8, and 15 of Cycle 12 (cycle length of 21 days)
Percentage of participants with total pathologic complete response (tpCR) according to RECIST v1.0
time frame: After surgery between Cycles 8 and 9 (cycle length of 21 days)
Percentage of participants with overall response according to RECIST v1.0
time frame: At Baseline and within 7 days prior to Day 1 of Cycles 3, 5, 7, and 9 (up to approximately 6 months)
Time to response (TTR) according to RECIST v1.0
time frame: At Baseline and within 7 days prior to Day 1 of Cycles 3, 5, 7, and 9 (up to approximately 6 months)
Event-free survival (EFS) defined as time to progression (local, regional, distant, or contralateral), disease recurrence, or death from any cause
time frame: During treatment (up to 1 year) and every 3 months until withdrawal of consent, death, or end of study (up to 5 additional years)
Overall survival (OS)
time frame: During treatment (up to 1 year) and every 3 months until withdrawal of consent, death, or end of study (up to 5 additional years)
Percentage of participants with adverse events (AEs)
time frame: Continuously from Baseline to withdrawal of consent, death, loss to follow-up, or end of study (up to 6 years)
Percentage of participants with formation of human anti-human antibodies (HAHAs) against Herceptin
time frame: At Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, and 18; then every 3 months until withdrawal of consent, death, loss to follow-up, or end of study (up to 6 years)
Percentage of participants with formation of HAHAs against recombinant human hyaluronidase (rHuPH20)
time frame: At Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, and 18; then every 3 months until withdrawal of consent, death, loss to follow-up, or end of study (up to 6 years)

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Adult women greater than or equal to (>/=) 18 years of age - Non-metastatic primary invasive adenocarcinoma of the breast clinical stage I to IIIC, including inflammatory and multicentric/multifocal breast cancer, with tumor size >/=1 centimeter (cm) by ultrasound or >/=2 cm by palpation, centrally confirmed HER2-positive - At least 1 measurable lesion in breast or lymph nodes (>/=1 cm by ultrasound or >/=2 cm by palpation), except for inflammatory carcinoma (T4d) - Baseline left ventricular ejection fraction (LVEF) >/=55% - Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 Exclusion Criteria: - History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma - Past or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and in situ carcinoma of the cervix - Metastatic disease - Any prior therapy with anthracyclines - Prior anti-HER2 therapy or biologic or immunotherapy - Serious cardiac illness - Pregnant or lactating women

Additional Information

Official title A Randomized Open-Label Study to Compare the Pharmacokinetics, Efficacy, and Safety of Subcutaneous (SC) Herceptin (Trastuzumab) With Intravenous (IV) Herceptin (Trastuzumab) Administered in Women With HER2-Positive Early Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.