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

  Hide Study Locations
Locations
Argentina
Tucuman, Argentina, T4000IAK
Tucuman, Argentina, T400IAK
Brazil
Salvador, BA, Brazil, 41253-190
Curitiba, PR, Brazil, 80060-900
Natal, RN, Brazil, 59040150
Itajai, SC, Brazil, 88301-220
Jau, SP, Brazil, 17210-080
Sao Paulo, SP, Brazil, 01317-000
Sao Paulo, SP, Brazil, 01246-000
Sorocaba, SP, Brazil, 18030-245
Canada, Quebec
Montreal, Quebec, Canada, H1T 2M4
Canada
Quebec, Canada, G1S 4L8
Colombia
Bogota, Colombia
Bogota, Colombia, 000472
Pereira, Colombia, 600004
Czech Republic
Olomouc, Czech Republic, 775 20
Pardubice, Czech Republic, 532 03
Praha, Czech Republic, 140 59
Praha, Czech Republic, 180 81
Estonia
Tallin, Estonia, 13419
Tartu, Estonia, 50406
France
Besancon, France, 25030
Grenoble, France, 38000
La Tronche, France, 38700
Le Mans, France, 72015
Paris, France, 75475
Reims, France, 51056
St Cloud, France, 92210
Germany
Berlin, Germany, 10117
Berlin, Germany, 10719
Bonn, Germany, 53113
Dortmund, Germany, 44137
Hannover, Germany, 30177
Leipzig, Germany, 04277
Lemgo, Germany, 32657
Offenbach, Germany, 63069
Rodewisch, Germany, 08228
Tübingen, Germany, 72076
Guatemala
Guatemala, Guatemala, 01010
Hong Kong
Hong Kong, Hong Kong, 852
Hungary
Budapest, Hungary, 1083
Gyor, Hungary, 9023
Szeged, Hungary, 6720
Israel
Jerusalem, Israel, 91120-01
Petach Tikva, Israel, 49100
Italy
Napoli, Campania, Italy, 80131
Cremona, Lombardia, Italy, 26100
Pavia, Lombardia, Italy, 27100
Korea, Republic of
Incheon, Korea, Republic of, 405-760
Seoul, Korea, Republic of, 135-710
Seoul, Korea, Republic of, 136-705
Seoul, Korea, Republic of, 138-736
Mexico
Obregon, Mexico, 85000
Toluca, Mexico, 50180
Panama
Panama, Panama, 0834-02723
Peru
Arequipa, Peru, 04001
Lima, Peru, 11
Lima, Peru, 41
Piura, Peru, 20011
San Isidro, Peru, Lima 27
Poland
Elblag, Poland, 82-300
Lublin, Poland, 20-090
Olsztyn, Poland, 10-513
Warszawa, Poland, 02-781
Russian Federation
Ivanovo, Russian Federation, 153040
Moscow, Russian Federation, 115478
Moscow, Russian Federation, 143423
Pyatigorsk, Russian Federation, 357502
Ryazan, Russian Federation, 390011
Saint-Petersburg, Russian Federation, 197758
Samara, Russian Federation, 443031
Saratov, Russian Federation, 410053
St Petersburg, Russian Federation, 197022
Stavropol, Russian Federation, 355045
Tula, Russian Federation, 300053
Vladimir, Russian Federation, 600009
Slovakia
Kosice, Slovakia, 04001
Poprad, Slovakia, 05801
South Africa
Bloemfontein, South Africa, 9301
Cape Town, South Africa, 7506
Johannesburg, South Africa, 2193
Pretoria, South Africa, 0081
Rondebosch, South Africa, 7700
Sandton, South Africa, 2196
Spain
Santiago de Compostela, La Coruña, Spain, 15706
Reus, Tarragona, Spain, 43204
Madrid, Spain, 28007
Valencia, Spain, 46010
Zaragoza, Spain, 50009
Sweden
Lund, Sweden, 22185
Uppsala, Sweden, 75185
Taiwan
Changhua, Taiwan, 500
Taipei, Taiwan, 00112
Taipei, Taiwan, 112
Taoyuan, Taiwan, 333
Thailand
Bangkok, Thailand, 10330
Bangkok, Thailand, 10400
Bangkok, Thailand, 10700
Songkhla, Thailand, 90110
Turkey
Antalya, Turkey, 07070
Istanbul, Turkey, 34390
Izmir, Turkey, 35340
Sıhhiye, ANKARA, Turkey, 06100
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 07, 2016