TriangleNCT00950300 · CITED IN SOURCE DOCUMENTS
A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2018-01-23
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.
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
Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery
Percentage of Participants With Pathological Complete Response (pCR)
Observed Ctrough of Trastuzumab After Surgery
Predicted Ctrough of Trastuzumab Prior to Surgery
Predicted Ctrough of Trastuzumab After Surgery
Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery
Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery
Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery
Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery
Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery
Cmax of Trastuzumab After Surgery
Tmax of Trastuzumab After Surgery
AUC21d of Trastuzumab After Surgery
Percentage of Participants With Total Pathological Complete Response (tpCR)
Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at Baseline
Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline
Percentage of Participants Who Experienced a Protocol-Defined Event
Event-Free Survival (EFS)
Percentage of Participants Who Died
Overall Survival (OS)
Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab
Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility 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 (immunohistochemical score \[IHC\] 3+ or in situ hybridization \[ISH\]-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 * Adequate organ function at Baseline 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- FEMALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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 IV 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.
- intervention Names
- Drug: 5-Fluorouracil
- Drug: Cyclophosphamide
- Drug: Docetaxel
- Drug: Epirubicin
- Drug: Herceptin IV [trastuzumab]
- label
- Herceptin IV + Chemotherapy
- type
- ACTIVE_COMPARATOR
- description
- 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 SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.
- intervention Names
- Drug: 5-Fluorouracil
- Drug: Cyclophosphamide
- Drug: Docetaxel
- Drug: Epirubicin
- Drug: Herceptin SC [trastuzumab]
- label
- Herceptin SC + Chemotherapy
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Herceptin IV + Chemotherapy
- Herceptin SC + Chemotherapy
- description
- 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.
- name
- 5-Fluorouracil
- type
- DRUG
- arm Group Labels
- Herceptin IV + Chemotherapy
- Herceptin SC + Chemotherapy
- description
- Participants will receive cyclophosphamide, 500 mg/m\^2 via IV bolus, on Day 1 of every 21-day cycle during Cycles 5 to 8.
- name
- Cyclophosphamide
- type
- DRUG
- arm Group Labels
- Herceptin IV + Chemotherapy
- Herceptin SC + Chemotherapy
- description
- Participants will receive docetaxel, 75 mg/m\^2 via IV infusion on Day 1 of every 21-day cycle during Cycles 1 to 4.
- name
- Docetaxel
- type
- DRUG
- arm Group Labels
- Herceptin IV + Chemotherapy
- Herceptin SC + Chemotherapy
- description
- 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.
- name
- Epirubicin
- type
- DRUG
- arm Group Labels
- Herceptin IV + Chemotherapy
- description
- 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.
- name
- Herceptin IV [trastuzumab]
- type
- DRUG
- arm Group Labels
- Herceptin SC + Chemotherapy
- description
- Herceptin will be administered as fixed dose 600 mg SC on Day 1 of each 21-day cycle for a total of 18 cycles.
- name
- Herceptin SC [trastuzumab]
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 596
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Pre-dose samples were obtained prior to surgery (Cycle 8). The observed Ctrough was recorded, averaged among all participants, and expressed in micrograms per milliliter (μg/mL).
- measure
- Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery
- time Frame
- Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
- description
- Participants were evaluated following eight cycles of treatment and after surgery to assess for pCR, defined as absence of neoplastic invasive cells in the breast according to pathologist examination. The percentage of participants with pCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.
- measure
- Percentage of Participants With Pathological Complete Response (pCR)
- time Frame
- After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
- secondary Outcomes
- description
- Pre-dose samples were obtained after surgery (Cycle 13). The observed Ctrough was recorded, averaged among all participants, and expressed in μg/mL.
- measure
- Observed Ctrough of Trastuzumab After Surgery
- time Frame
- Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
- description
- Predicted Ctrough at pre-dose prior to surgery (Cycle 8) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL.
- measure
- Predicted Ctrough of Trastuzumab Prior to Surgery
- time Frame
- Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
- description
- Predicted Ctrough at pre-dose after surgery (Cycle 13) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL.
- measure
- Predicted Ctrough of Trastuzumab After Surgery
- time Frame
- Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
- description
- Pre-dose samples were obtained prior to surgery (Cycle 8). The number of participants who had an observed Ctrough \>20 μg/mL was reported.
- measure
- Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery
- time Frame
- Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
- description
- Pre-dose samples were obtained after surgery (Cycle 13). The number of participants who had an observed Ctrough \>20 μg/mL was reported.
- measure
- Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery
- time Frame
- Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
- description
- PK samples were obtained prior to surgery (Cycle 7). The Cmax during Cycle 7 was recorded, averaged among all participants, and expressed in μg/mL.
- measure
- Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery
- time Frame
- Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
- description
- PK samples were obtained prior to surgery (Cycle 7). The Tmax during Cycle 7 was recorded, averaged among all participants, and expressed in days.
- measure
- Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery
- time Frame
- Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
- description
- PK samples were obtained prior to surgery (Cycle 7). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 7 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in days multiplied by micrograms per milliliters (d\*μg/mL).
- measure
- Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery
- time Frame
- Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
- description
- PK samples were obtained after surgery (Cycle 12). The Cmax during Cycle 12 was recorded, averaged among all participants, and expressed in μg/mL.
- measure
- Cmax of Trastuzumab After Surgery
- time Frame
- Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
- description
- PK samples were obtained after surgery (Cycle 12). The Tmax during Cycle 12 was recorded, averaged among all participants, and expressed in days.
- measure
- Tmax of Trastuzumab After Surgery
- time Frame
- Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
- description
- PK samples were obtained after surgery (Cycle 12). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 12 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in d\*μg/mL.
- measure
- AUC21d of Trastuzumab After Surgery
- time Frame
- Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
- description
- Participants were evaluated following eight cycles of treatment and after surgery to assess for tpCR, defined as absence of neoplastic invasive cells in the breast and axillary lymph nodes according to pathologist examination. The percentage of participants with tpCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.
- measure
- Percentage of Participants With Total Pathological Complete Response (tpCR)
- time Frame
- After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
Full study description
- brief 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.
Source references
- references
- citation
- Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs Intravenous Trastuzumab for Patients With ERBB2-Positive Early Breast Cancer: Final Analysis of the HannaH Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 May 1;5(5):e190339. doi: 10.1001/jamaoncol.2019.0339. Epub 2019 May 9.
- pmid
- 30998824
- type
- DERIVED
- citation
- Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. doi: 10.1016/S1470-2045(12)70329-7. Epub 2012 Aug 9.
- pmid
- 22884505
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice