A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Trastuzumab (Herceptin) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00950300
First received: July 30, 2009
Last updated: February 1, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Breast Cancer
Drug: 5-Fluorouracil
Drug: Cyclophosphamide
Drug: Docetaxel
Drug: Epirubicin
Drug: Herceptin IV
Drug: Herceptin SC
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]

Enrollment: 596
Study Start Date: October 2009
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Herceptin IV + Chemotherapy
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.
Drug: 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.
Drug: 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.
Drug: 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.
Drug: 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.
Drug: Herceptin IV
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.
Other Name: Trastuzumab
Experimental: Herceptin SC + Chemotherapy
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.
Drug: 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.
Drug: 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.
Drug: 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.
Drug: 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.
Drug: Herceptin SC
Herceptin will be administered as fixed dose 600 mg SC on Day 1 of each 21-day cycle for a total of 18 cycles.
Other Name: Trastuzumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950300

  Show 103 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00950300     History of Changes
Other Study ID Numbers: BO22227  2008-007326-19 
Study First Received: July 30, 2009
Last Updated: February 1, 2016
Health Authority: China: Hong Kong Department of Health

Additional relevant MeSH terms:
Trastuzumab
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Docetaxel
Epirubicin
Fluorouracil
Alkylating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on February 11, 2016