Efficacy and Safety Evaluating Study of CT-P6 in Her2 Positive Early Breast Cancer

Phase 3 Efficacy and Safety Study of CT-P6 and Herceptin as Neoadjuvant and Adjuvant Treatment in Patients With Her2-positive Early Breast Cancer

This study will determine whether CT-P6 and Herceptin are equivalent in patients with early-stage breast cancer undergoing neoadjuvant chemotherapy. Our hypothesis is that the pathologic complete response rate will be equivalent in patients treated with neoadjuvant CT-P6 or Herceptin. Patients will receive 8 cycles of neoadjuvant systemic therapy and up to 10 cycles of therapy in the adjuvant setting.

Study Overview

• Status: Completed
• Conditions: HER2-positive Carcinoma of Breast
• Intervention / Treatment: Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 562
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1185
  • Córdoba, Argentina, X5006IKK
  • Quilmes, Argentina, B1878DVB
  • Rosario, Argentina, S2000KDS
  • San Salvador De Jujuy, Argentina, 4600
  • Santa Rosa, Argentina, 6300
• Belarus
  • Brest, Belarus, 224027
  • Minsk, Belarus, 220013
  • Minsk, Belarus, 223040
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
• Chile
  • Santiago, Chile, 6640166
  • Temuco, Chile, 4810469
• France
  • Nancy, France, 54511
• Georgia
  • Tbilisi, Georgia, 0112
  • Tbilisi, Georgia, 0144
  • Tbilisi, Georgia, 0159
  • Tbilisi, Georgia, 0186
  • Tbilisi, Georgia, 0177
• Hungary
  • Budapest, Hungary, 1083
  • Debrecen, Hungary, 4032
• India
  • Bangalore, India, 560099
  • Chennai, India, 600017
  • Chennai, India, 600035
  • Delhi, India, 110095
  • Jaipur, India, 302017
  • Kolkata, India, 700016
  • Mumbai, India, 400 012
  • Nashik, India, 422004
  • Nashik, India, 422005
  • New Delhi, India, 110076
  • Pune, India, 411001
• Italy
  • Bari, Italy, 70124
  • Pavia, Italy, 27100
  • Piacenza, Italy, 29100
  • Rimini, Italy, 47900
• Japan
  • Tokyo, Japan
• Latvia
  • Daugavpils, Latvia, LV-5417
  • Riga, Latvia, LV-1079
• Mexico
  • Acapulco, Mexico, 39670
  • Monterrey, Mexico, 64710
• Peru
  • Arequipa, Peru
  • Arequipa, Peru, 4020
  • Lima, Peru, 34
  • Trujillo, Peru
• Philippines
  • Cebu, Philippines, 6000
  • Makati, Philippines, 1229
  • Manila, Philippines, 1008
  • Pasig, Philippines, 1600
  • Quezon City, Philippines, 1102
  • San Juan City, Philippines, 1502
  • Taguig, Philippines, 1634
• Poland
  • Gdansk, Poland, 80219
  • Lodz, Poland, 93513
  • Warsaw, Poland, 04125
• Portugal
  • Lisbon, Portugal, 1099023
• Romania
  • Brasov, Romania, 500152
  • Bucharest, Romania, 022328
  • Bucharest, Romania, 010976
  • Cluj-Napoca, Romania, 400058
  • Cluj-Napoca, Romania, 400015
  • Suceava, Romania, 720237
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
  • Kazan, Russian Federation, 420029
  • Krasnoyarsk, Russian Federation, 660133
  • Kursk, Russian Federation, 305035
  • Moscow, Russian Federation, 115478
  • Moscow, Russian Federation, 143423
  • Nizhny Novgorod, Russian Federation, 603081
  • Novosibirsk, Russian Federation, 630099
  • Obninsk, Russian Federation, 249036
  • Omsk, Russian Federation
  • Samara, Russian Federation, 443066
  • Saransk, Russian Federation, 430032
  • St. Petersburg, Russian Federation, 197022
  • St. Petersburg, Russian Federation, 197758
  • St. Petersburg, Russian Federation, 188663
  • St. Petersburg, Russian Federation, 194017
• South Africa
  • Cape Town, South Africa, 7570
  • George, South Africa, 6530
  • Johannesburg, South Africa, 2193
  • Johannesburg, South Africa, 2196
  • Port Elizabeth, South Africa, 6045
  • Pretoria, South Africa, 0002
• Spain
  • Sevilla, Spain, 41071
  • Zaragoza, Spain, 50009
• Taiwan
  • Kaohsiung, Taiwan, 807
  • Taichung City, Taiwan, 40447
  • Taipei, Taiwan, 100
• Ukraine
  • Cherkasy, Ukraine, 18009
  • Donetsk, Ukraine, 83092
  • Kharkiv, Ukraine, 61070
  • Kherson, Ukraine, 73000
  • Khmel'nyts'kyy, Ukraine, 29000
  • Poltava, Ukraine, 36021
  • Sumy, Ukraine, 40022
  • Uzhhorod, Ukraine, 88014
  • Vinnytsya, Ukraine, 21029
  • Zaporizhzhia, Ukraine, 69040

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient who has histologically confirmed and newly diagnosed breast cancer
• Patient who has clinical stage I, II, or IIIa operable breast cancer according to AJCC (American Joint Committee on Cancer) Breast Cancer Staging 7th edition
• Patient who has HER2-positive status confirmed locally, defined as 3+ score by IHC (immuno-histochemistry).

Exclusion Criteria:

• Patient who has bilateral breast cancer
• Patient who has received prior treatment for breast cancer, including chemotherapy, biologic therapy, hormone therapy, immunotherapy, radiation or surgery, including any prior therapy with anthracyclines.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Trastuzumab	Drug: Trastuzumab; Trastuzumab 6mg/kg is ongoing to be administered for both arms after 8mg/kg loading dose.; Other Names: Herceptin
Experimental: CT-P6	Drug: Trastuzumab; Trastuzumab 6mg/kg is ongoing to be administered for both arms after 8mg/kg loading dose.; Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients Achieving Pathological Complete Response Defined as the Absence of Invasion Tumor Cells in the Breast and in Axillary Lymph Nodes, Regardless of Ductal Carcinoma in Situ (DCIS)	Subject who went through Neoadjuvant period completely (24 weeks), will receive surgery within 3-6 weeks after last treatment of neoadjuvant period. The primary endpoint, Pathological complete response, will be assessed using resected bio-specimens collected in breast and axilla during a surgery.	After Neo-adjuvant therapy and Surgery (up to 30 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients Achieving Pathological Complete Response (pCR) of the Breast Regardless of DCIS With Positive or Unknown Nodal Status	Subject who went through Neoadjuvant period completely (24 weeks), will receive surgery within 3-6 weeks after last treatment of neoadjuvant period. The secondary endpoint, other than pCR of breast and axillary nodes ragardless of DCIS which was primary endpoint, will be assessed using resected bio-specimens collected in breast and axilla during a surgery.	After Neo-adjuvant therapy and Surgery (up to 30 weeks)
The Percentage of Patients Achieving Pathological Complete Response of the Breast and Axillary Nodes With Absence of DCIS	Subject who went through Neoadjuvant period completely (24 weeks), will receive surgery within 3-6 weeks after last treatment of neoadjuvant period. The secondary endpoint, other than pCR of breast and axillary nodes ragardless of DCIS which was primary endpoint, will be assessed using resected bio-specimens collected in breast and axilla during a surgery.	After Neo-adjuvant therapy and Surgery (up to 30 weeks)
Overall Response Rate (ORR) From Local Review	The ORR was defined as the proportion of patients with a BOR of CR or PR as assessed by RECIST guideline Version 1.1 during the Nedadjuvant Period.	After Neo-adjuvant therapy (up to 24 weeks)
Disease-free Survival	Patients who underwent breast surgery were included in the DFS analysis. Disease-free survival was defined as the interval between the date of breast surgery and disease progression, recurrence, or death from any cause, whichever occurred first. Only a recurrence or progression of disease that occurred before beginning another anticancer therapy was regarded as an event.	Up to 3 years from the day of last patient enrollment (during whole study period)
Progression-Free Survival	Progression-free survival was defined as the interval between randomization and disease progression, recurrence, or death from any cause, whichever occurred first. Only a recurrence or progression of disease that occurred before beginning another anticancer therapy was regarded as an event.	Up to 3 years from the day of last patient enrollment (during whole study period)
Overall Survival	Overall survival was defined as the interval between randomization and death from any cause.	Up to 3 years from the day of last patient enrollment (during whole study period)
The Number of Patients Who Had Progressive Disease or Recurrence	If recurrence or progression of disease occurred at any time during the study, the progressed tumor site was recorded in the "recurrence or progression of disease" eCRF page as local, regional, or distant, with diagnostic method and whether positive cytology or histology or not. The resulting recurrence or progression of disease information was summarized as secondary endpoint.	Up to 3 years from the day of last patient enrollment (during whole study period)
Maximum Serum Concentration After Administration (Cmax) in Each Cycle	Pharmacokinetic samples were collected before study drug (CT-P6 or US-licensed Herceptin) administration (within 15 minutes prior to the beginning of the study drug infusion) and within 15 minutes after the end of the study drug infusion for each cycle during the Neoadjuvant Period. After the completion of treatment, an additional PK sample was collected at the EOT1.	End of each treatment cycles, up to 24 weeks (during neoadjuvant period)
Trough Serum Concentration (Ctrough) in Each Cycle	Pharmacokinetic samples were collected before study drug (CT-P6 or US-licensed Herceptin) administration (within 15 minutes prior to the beginning of the study drug infusion) and within 15 minutes after the end of the study drug infusion for each cycle during the Neoadjuvant Period. After the completion of treatment, an additional PK sample was collected at the EOT1.	Pre-infusion of cycles 1 to 8 during neoadjuvant period

Collaborators and Investigators

• Sponsor: Celltrion
• Collaborators: Nippon Kayaku Co., Ltd.

Publications and helpful links

General Publications

• Stebbing J, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Pikiel J, Eniu AE, Li RK, Tiangco B, Lee SJ, Kim S. Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial. Breast Cancer Res Treat. 2021 Aug;188(3):631-640. doi: 10.1007/s10549-021-06240-5. Epub 2021 Jun 20.
• Esteva FJ, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskiy D, Pikiel J, Eniu AE, Li RK, Rusyn AV, Tiangco B, Lee SJ, Lee SY, Yu SY, Stebbing J. Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial. Cancer Chemother Pharmacol. 2019 Oct;84(4):839-847. doi: 10.1007/s00280-019-03920-4. Epub 2019 Aug 19.
• Stebbing J, Baranau Y, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskii D, Pikiel J, Eniu A, Komov D, Morar-Bolba G, Li RK, Rusyn A, Lee SJ, Lee SY, Esteva FJ. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol. 2017 Jul;18(7):917-928. doi: 10.1016/S1470-2045(17)30434-5. Epub 2017 Jun 4. Erratum In: Lancet Oncol. 2017 Aug;18(8):e433. Lancet Oncol. 2017 Sep;18(9):e510.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): May 26, 2016
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: June 11, 2014
• First Submitted That Met QC Criteria: June 11, 2014
• First Posted (Estimate): June 13, 2014

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: CT-P6 3.2; 2013-004525-84 (EudraCT Number)