TriangleNCT00976989 · CITED IN SOURCE DOCUMENTS
A Study of Pertuzumab in Combination With Herceptin and Chemotherapy in Participants With HER2-Positive Breast Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2017-02-06
This 3 arm study will assess the tolerability, safety and efficacy of 3 neoadjuvant treatment regimens in participants with locally advanced, inflammatory or early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Before surgery, participants will be randomized to receive either A) 6 cycles of pertuzumab plus trastuzumab (Herceptin), with 5-fluorouracil/epirubicin/cyclophosphamide (FEC) for cycles 1-3 and docetaxel for cycles 4-6, or B) FEC for cycles 1-3 followed by pertuzumab plus trastuzumab with docetaxel for cycles 4-6, or C) 6 cycles of pertuzumab plus trastuzumab with docetaxel and carboplatin. Pertuzumab will be administered at a loading dose of 840 mg intravenously (iv), then 420 mg iv 3-weekly, trastuzumab at a loading dose of 8 mg/kg iv, then 6 mg/kg iv 3-weekly, docetaxel at 75 mg/m\^2 iv, increased to 100 mg/m\^2 iv 3-weekly, and FEC and carboplatin iv 3-weekly at standard doses. Following surgery participants will receive trastuzumab 6 mg/kg iv 3-weekly for a total of 1 year, as well as adequate chemo-, radio- and hormone therapy. Anticipated time on study treatment is 4-12 months, and target sample size is 200-300.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator
Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period
Efficacy: Percentage of Participants With Complete Pathological Response (pCR)
Efficacy: Clinical Response Rate
Efficacy: Time to Clinical Response
Efficacy: Percentage of Participants Achieving Breast Conserving Surgery
Efficacy: Percentage of Participants Without an Overall Survival (OS) Event
Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event
Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event
Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD)
Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events
Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * female participants, age \>/=18 years * advanced, inflammatory or early stage unilateral invasive breast cancer * HER2-positive breast cancer * baseline left ventricular ejection fraction (LVEF) \>/=55% Exclusion Criteria: * metastatic disease (Stage IV) or bilateral breast cancer * previous anticancer therapy or radiotherapy for any malignancy * other malignancy, except for carcinoma in situ of the cervix, or basal cell carcinoma * clinically relevant cardiovascular disease * current chronic treatment with corticosteroids of \>10mg methylprednisolone or equivalent
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- FEMALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
- intervention Names
- Drug: Pertuzumab
- Drug: Trastuzumab
- Drug: FEC
- Drug: Docetaxel
- label
- T+P Concomitant Anthracycline-based chemotherapy
- type
- EXPERIMENTAL
- description
- FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.
- intervention Names
- Drug: Pertuzumab
- Drug: Trastuzumab
- Drug: FEC
- Drug: Docetaxel
- label
- T+P Sequential Anthracycline-based chemotherapy
- type
- EXPERIMENTAL
- description
- Trastuzumab, carboplatin, docetaxel (TCH) and pertuzumab (P) every three weeks, for six cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.
- intervention Names
- Drug: Pertuzumab
- Drug: TCH
- label
- T+P Concomitant Non-Anthracycline chemotherapy
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- T+P Concomitant Anthracycline-based chemotherapy
- T+P Concomitant Non-Anthracycline chemotherapy
- T+P Sequential Anthracycline-based chemotherapy
- description
- 840 mg loading dose intravenously (IV), then 420 mg IV 3-weekly.
- name
- Pertuzumab
- other Names
- Perjeta
- type
- DRUG
- arm Group Labels
- T+P Concomitant Anthracycline-based chemotherapy
- T+P Sequential Anthracycline-based chemotherapy
- description
- 8 mg/kg loading dose IV, then 6 mg/kg every 3 weeks.
- name
- Trastuzumab
- other Names
- Herceptin
- type
- DRUG
- arm Group Labels
- T+P Concomitant Anthracycline-based chemotherapy
- T+P Sequential Anthracycline-based chemotherapy
- description
- 5-fluorouracil 500 mg/m\^2, epirubicin 100 mg/m\^2 and cyclophosphamide 600 mg/m\^2.
- name
- FEC
- type
- DRUG
- arm Group Labels
- T+P Concomitant Anthracycline-based chemotherapy
- T+P Sequential Anthracycline-based chemotherapy
- description
- 75 mg/m\^2 for the first dose; 100 mg/m\^2 if no dose limiting toxicity occurs.
- name
- Docetaxel
- type
- DRUG
- arm Group Labels
- T+P Concomitant Non-Anthracycline chemotherapy
- description
- Trastuzumab followed by carboplatin at target area under the plasma concentration-time curve (AUC) 6 and docetaxel at a starting dose of 75 mg/m\^2. All treatments were given every three weeks by the IV route.
- name
- TCH
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 225
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Left ventricular systolic dysfunction (LVSD) as assessed by the Investigator, including Grade 3, 4 or 5 symptomatic LVSD with symptomatic cardiac events.
- measure
- Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator
- time Frame
- From baseline up to approximately 3.5 years
- description
- Percentage of participants with LVEF measures decline of ≥ 10% from baseline and to a value of \<50% during the pre-operative (neoadjuvant) period.
- measure
- Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period
- time Frame
- From baseline up to approximately 18 weeks
- secondary Outcomes
- description
- pCR is defined as the absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. pCR is evaluated after 6 cycles of treatment and surgery or following withdrawal from the study whichever occurs sooner.
- measure
- Efficacy: Percentage of Participants With Complete Pathological Response (pCR)
- time Frame
- At surgery, after 18 weeks (6 cycles) of treatment
- description
- Tumor response is defined as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) and is identified as per local practice. Clinical response rate is defined as the percentage of participants who achieve a response of CR or PR at any time pre-surgery. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by mammogram or magnetic resonance imaging (MRI) and clinical breast examination (CBE), CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions.
- measure
- Efficacy: Clinical Response Rate
- time Frame
- During each 3-week cycle of 6 total cycles: up to 18 weeks
- description
- Time to clinical response is defined as the time from the date of first dose received to the first date of assessment of clinical response. Clinical response is defined as a response of CR or PR at any time pre-surgery. Per RECIST v1.0 for target lesions and assessed by mammogram or MRI and CBE, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions.
- measure
- Efficacy: Time to Clinical Response
- time Frame
- Up to 18 weeks
- description
- This is the percentage of participants who achieved breast conserving surgery out of the intent-to-treat population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant (pre-operative) treatment.
- measure
- Efficacy: Percentage of Participants Achieving Breast Conserving Surgery
- time Frame
- At approximately 18 weeks
- description
- Overall survival (OS) was defined as the time from randomization to the date of death from any cause. Participants who were alive or lost to follow-up were censored at the last known alive date. Participants with no post-baseline information were censored at the date of randomization plus one day.
- measure
- Efficacy: Percentage of Participants Without an Overall Survival (OS) Event
- time Frame
- From baseline to end of study up to 5 years
- description
- The DFS was defined as the time from the first date of no disease (i.e., date of surgery) to the first documentation of progressive disease (PD) or death. PD was assessed using RECIST v1.0 and MRI and CBE. It was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Any evidence of contralateral disease in situ was not considered as PD. Participants who were withdrawn from the study without documented PD were censored at the date of the last assessment when the participant was known to be disease-free.
- measure
- Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event
- time Frame
- From baseline to end of study up to 5 years
- description
- Progression-free survival was defined as the time from the date of randomization to the first documentation of PD or death from any cause, whichever occurred first. PD was assessed using RECIST v1.0 and MRI and CBE. It was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Participants who were withdrawn from the study without documented PD were censored at the date of the last assessment when the participant was known to be free from PD. Participants without post-baseline assessments but known to be alive were censored at the time of randomization plus one day.
- measure
- Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event
- time Frame
- From baseline to end of study up to 5 years
- description
- Percentage of participants with signs or symptoms of cardiac events.
- measure
- Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD)
- time Frame
- From Baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years)
- description
- Percentage of participants with LVEF events without signs or symptoms of cardiac events.
- measure
- Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events
- time Frame
- From baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years)
- description
- Maximum decrease in LVEF measures is the change from baseline at worst treatment value. LVEF is measured as percentage.
- measure
- Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures
- time Frame
- From baseline up to approximately 3.5 years
Full study description
- brief Summary
- This 3 arm study will assess the tolerability, safety and efficacy of 3 neoadjuvant treatment regimens in participants with locally advanced, inflammatory or early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Before surgery, participants will be randomized to receive either A) 6 cycles of pertuzumab plus trastuzumab (Herceptin), with 5-fluorouracil/epirubicin/cyclophosphamide (FEC) for cycles 1-3 and docetaxel for cycles 4-6, or B) FEC for cycles 1-3 followed by pertuzumab plus trastuzumab with docetaxel for cycles 4-6, or C) 6 cycles of pertuzumab plus trastuzumab with docetaxel and carboplatin. Pertuzumab will be administered at a loading dose of 840 mg intravenously (iv), then 420 mg iv 3-weekly, trastuzumab at a loading dose of 8 mg/kg iv, then 6 mg/kg iv 3-weekly, docetaxel at 75 mg/m\^2 iv, increased to 100 mg/m\^2 iv 3-weekly, and FEC and carboplatin iv 3-weekly at standard doses. Following surgery participants will receive trastuzumab 6 mg/kg iv 3-weekly for a total of 1 year, as well as adequate chemo-, radio- and hormone therapy. Anticipated time on study treatment is 4-12 months, and target sample size is 200-300.
Source references
- references
- citation
- Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortes J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35. doi: 10.1016/j.ejca.2017.10.021. Epub 2017 Dec 8.
- pmid
- 29223479
- type
- DERIVED
- citation
- Swain SM, Schneeweiss A, Gianni L, Gao JJ, Stein A, Waldron-Lynch M, Heeson S, Beattie MS, Yoo B, Cortes J, Baselga J. Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. Ann Oncol. 2017 Apr 1;28(4):761-768. doi: 10.1093/annonc/mdw695.
- pmid
- 28057664
- type
- DERIVED
- citation
- Schneeweiss A, Chia S, Hegg R, Tausch C, Deb R, Ratnayake J, McNally V, Ross G, Kiermaier A, Cortes J. Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Res. 2014 Jul 8;16(4):R73. doi: 10.1186/bcr3690.
- pmid
- 25005255
- type
- DERIVED
- citation
- Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortes J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. doi: 10.1093/annonc/mdt182. Epub 2013 May 22.
- pmid
- 23704196
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-130e27b2e4549d05257f
- requested nct id
- NCT00976989
- primary nct id
- NCT00976989
- source kind
- fda_spl_label
- source record id
- 9d068707-f189-4f0f-a74e-17bbe1f10476
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- payload sha256
- 887125987e3621709dd1da4ac1cab8b9b8723c6c73f951411cca487a1f0ffdc2
- payload
- application numbers
- BLA761170
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-130e27b2e4549d05257f
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT00976989
- occurrences
- context exact
- enous pertuzumab and intravenous trastuzumab administered in combination with chemotherapy in adults with HER2-overexpressing early breast cancer (NCT00545688, NCT00976989, NCT02132949, NCT01358877) and additional pharmacokinetic and safety data that demonstrated comparable pharmacokinetics and safety profiles between PHESGO and
- end
- 530
- exact text
- NCT00976989
- start
- 519
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00500.json
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- source json pointer
- /results/62/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 9d068707-f189-4f0f-a74e-17bbe1f10476
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 9be4f0f055936f08522f6010412aca48c496a88a6af1fc91f1af16171d45df83
- spl effective time
- 20260521
- spl set id
- 27dd5e6b-72cd-458d-a015-cf4dab5800da
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-2672550f2248a9f2f191
- requested nct id
- NCT00976989
- primary nct id
- NCT00976989
- source kind
- fda_spl_label
- source record id
- dfebfe9c-a0c5-41d8-bf11-ed643627e264
- source file sha256
- 24c521d95bd19e54a354ae592997052a3a1b19254da1496b3a98a5e9bac4ed08
- payload sha256
- 7d7b8a849a477e3e32c40d062c1d513be24f51ea9c2c179ca805b5db3787f8f4
- payload
- application numbers
- BLA125409
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-2672550f2248a9f2f191
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT00976989
- occurrences
- context exact
- up N=57 N=57 N=55 N=50 pCR , n (%) [95% CI] 17 (29.8%) [18.4, 43.4] 31 (54.4%) [40.7, 67.6] 11 (20.0%) [10.4, 33.0] 13 (26.0%) [14.6, 40.3] TRYPHAENA TRYPHAENA(NCT00976989) was a three-arm, randomized (1:1:1) study in the neoadjuvant setting conducted in 225 patients with HER2-positive locally advanced, operable, or inflammatory
- end
- 9011
- exact text
- NCT00976989
- start
- 9000
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00700.json
- source file sha256
- 24c521d95bd19e54a354ae592997052a3a1b19254da1496b3a98a5e9bac4ed08
- source json pointer
- /results/40/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- dfebfe9c-a0c5-41d8-bf11-ed643627e264
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- b02ea8f0ffd26b753cb95acefcab833ce6266219d5ab22496231848e6c8edc2d
- spl effective time
- 20260430
- spl set id
- 17f85d17-ab71-4f5b-9fe3-0b8c822f69ff
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-93fe52ce7bafec3a3fc6
- requested nct id
- NCT00976989
- primary nct id
- NCT00976989
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source file sha256
- 862f78faa9e4cbedc19f9ffcaeba97e029ba51b72bb3b81fc67aa8b6adf96904
- payload sha256
- f778f5a72104666563dcf6452375cf39f60b1025181747dfeffb388d174962f2
- payload
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-93fe52ce7bafec3a3fc6
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT00976989
- occurrences
- context exact
- s in long-term efficacy outcomes.[<a href="#cit/section_6.123">123</a>] </li></ul></div></li><li>The open-label, randomized, phase II <a href="/clinicaltrials/NCT00976989">TRYPHAENA</a> trial (NCT00976989) sought to evaluate the tolerability and activity associated with trastuzumab and pertuzumab.[<a href="#cit/section_6.124">12
- end
- 406084
- exact text
- NCT00976989
- start
- 406073
- context exact
- <a href="#cit/section_6.123">123</a>] </li></ul></div></li><li>The open-label, randomized, phase II <a href="/clinicaltrials/NCT00976989">TRYPHAENA</a> trial (NCT00976989) sought to evaluate the tolerability and activity associated with trastuzumab and pertuzumab.[<a href="#cit/section_6.124">124</a>][<a href="/Common/PopUps/pop
- end
- 406118
- exact text
- NCT00976989
- start
- 406107
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/nci/raw/29bf1e5a1d739974ed.html
- source file sha256
- 862f78faa9e4cbedc19f9ffcaeba97e029ba51b72bb3b81fc67aa8b6adf96904
- source json pointer
- Source null
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source retrieved at
- 2026-09-09T23:21:35.419733+00:00
- source string basis
- UTF-8_text_with_universal_newline_translation
- source string sha256
- 536430925e3b0008edd3fb69a869d5645bd6b6dc5c84c21ddf1b3e24f089874c
- source title
- Breast Cancer Treatment (PDQ®)–Health Professional Version
- source update dates
- context
- Updated: April 25, 2025
- datetime
- 2025-04-25T12:00:00Z
- display
- April 25, 2025
Preserved source evidence · Not medical advice