Clinical trial NCT01875367: Phase III to Evaluate Patient´s Preference of Subcutaneous Trastuzumab vs Intravenous in HER2+ Advanced Breast Cancer
Official title: Phase III Trial to Evaluate Patient´s Preference of Subcutaneous Trastuzumab vs Intravenous (IV) Administration in HER2 Positive Advanced Breast Cancer Who Have Received IV Trastuzumab at Least 4 Months and Without Disease Progression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Subcutaneous trastuzumab
Intravenous trastuzumab
HER2 positive
Advanced Breast Cancer
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
First posted: 2013-06-11
Enrollment: 166
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients, from the randomization and before starting subcutaneous trastuzumab (SC-t), received an additional intravenous (IV-t) cycle. After receiving this cycle, patients started the treatment with the study medication, SC-t at a fixed dose of 600 mg every 3 weeks (+3 days) for 4 cycles (2 administered from the injection of a vial in a syringe and 2 with the single-use injection device \[SID\]), being randomized 1:1 in two arms of treatment without washout period:

* Arm A (1 cycle of IV-t followed by 2 cycles of SC-t with vial followed by 2 cycles of SC-t with SID)
* Arm B (1 cycle of IV-t followed by 2 cycles of SC-t with SID followed by 2 cycles of SC-t with vial)

This is not a cross-over study.
Primary purpose: TREATMENT

Brief summary: GEICAM/2012-07 is a study phase III, prospective, open, randomized, multicenter and national designed to assess patient preference for intravenous (IV) or subcutaneous (SC) of trastuzumab, and within the SC by the administration through the vial or device self-administration in patients with disseminated breast cancer HER2.

Detailed description: Approximately 195 patients will be included to receive subcutaneous trastuzumab a fixed dose of 600 mg every 3 weeks for 4 cycles (2 administered from the injection of a vial with a syringe and 2 with the injection device). Following administration of these four cycles, the patient will decide whether or not to continue with the subcutaneous formulation of trastuzumab every 3 weeks until progression (out of the study). Since the randomization in the study until the start with subcutaneous trastuzumab, patients will receive a treatment cycle of intravenous trastuzumab as usual.

Main objective: Proportion of patients indicate a preference for the use of subcutaneous vs intravenous trastuzumab.

This principal primary objective will be analyzed with the answers to questionnaire of experiences and preferences of the patients (Principal endpoint) The duration of the study has been estimated after 34 months.

Eligibility criteria: Inclusion Criteria:

* Woman, 18 years old or upper.
* Patient with advanced breast cancer with human epidermal growth factor receptor 2 (HER 2) positive histologically confirmed. The criteria for positivity HER 2 are:

  1. immuno-histochemistry (IHC) 3+ (\>10% of tumor cells with complete and intense membrane staining)
  2. IHC 2+ with fluorescent in situ hybridization (FISH) / Chromogenic in situ hybridization (CISH) / silver-enhanced in situ hybridization (SISH) + for HER 2 amplification (\*)
  3. FISH / CISH / SISH + for HER 2 amplification (\*) (\*) Defined as the ratio of copies of HER 2/neu and copies of centromere of chromosome 17 (CEP17)\> 2.2, or a number of copies of HER 2/neu\> 6, as per local laboratory criteria.
* Patient receiving trastuzumab with or without chemotherapy or hormonal therapy for at least 4 months.
* No evidence of disease progression (clinical and / or radiological) for at least 4 months before inclusion in the study and with a life expectancy of at least 3 months.
* Adequate performance status: Eastern Cooperative Oncology Group (ECOG) \<2.
* Adequate bone marrow function, liver and kidney
* Proper cardiac function (LVEF within normal limits the center, measured by echocardiography or MUGA).
* The patient must have been informed of the study and must sign and date informed consent document for entry into the trial.
* The patient must be willing and able to comply with study procedures and be available to answer the study questionnaires.

Exclusion Criteria:

* Patients with no advanced breast cancer.
* Breast cancer patients with tumors HER 2-negative.
* The patient has another active malignancy other than breast adenocarcinoma; are excluded the non-melanoma skin cancer or any other properly treated in situ neoplasia. Patients with a history of malignancy, if they bear\> 5 years without evidence of disease could be included.
* The patient has uncontrolled brain metastases.
* Concomitant administration, or in the 4 weeks prior to study entry, of other experimental treatment.
* Known hypersensitivity to trastuzumab or to any of its components.
* Patients with severe dyspnea at rest or requiring supplemental oxygen.
* Heart disease or serious medical pathological prevent trastuzumab administration: documented history of congestive cardiac insufficiency (CCI), high-risk arrhythmias uncontrolled angina requiring medication, clinically significant valvular disease, history of myocardial infarction or evidence of transmural infarction on ECG or hypertension poorly controlled.
* Presence of any concomitant serious systemic disease that is incompatible with the study (at the discretion of the investigator).
* The patient is pregnant or lactating. Women of childbearing potential should undergo pregnancy testing blood or urine within 14 days prior to inclusion as institutional rules and use a non-hormonal contraceptive suitable: intrauterine device, barrier method (condom or diaphragm) also used in conjunction with spermicidal cream, total abstinence or surgical sterilization, during treatment with the study drugs and for 6 months following the end of treatment.

Primary outcomes:
measure: Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference
timeFrame: Up to 12 weeks
measure: Percentage of Medical Staff With Intravenous vs. Subcutaneous Preference
timeFrame: Up to 12 weeks
measure: Percentage of Medical Staff Subcutaneous Device vs. Vial Preference
timeFrame: Up to 12 weeks
measure: Patient Time in Healthcare Unit and Sitting in Chair/Bed
timeFrame: An average of 4 months
measure: The Number of Participants Who Experienced Adverse Events (AE)
timeFrame: Through study treatment, an average of 12 weeks
Other outcomes:
Locations:
city: Granollers
country: Spain
facility: Hospital General Universitario de Granollers
state: Barcelona
city: Mataró
country: Spain
facility: Hospital de Mataró
state: Barcelona
city: Sant Joan Despí
country: Spain
facility: Hospital Sant Joan Despí Moises Broggi
state: Barcelona
city: Plasencia
country: Spain
facility: Hospital Virgen del Puerto de Plasencia
state: Cáceres
city: Manacor
country: Spain
facility: Hospital de Manacor
state: Illes Balears
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
state: Madrid
city: Leganés
country: Spain
facility: Hospital Universitario Severo Ochoa
state: Madrid
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Univesitario Quirón Madrid
state: Madrid
city: Cartagena
country: Spain
facility: Hospital Universitario Santa Lucía
state: Murcia
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Málaga
city: Reus
country: Spain
facility: Hospital Universitario San Joan de Reus
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Lleida
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Ávila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
Study officials:
affiliation: Hospitales Universitarios Virgen del Rocío
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Ciruelos EM, Montano A, Rodriguez CA, Gonzalez-Flores E, Lluch A, Garrigos L, Quiroga V, Anton A, Malon D, Chacon JI, Velasco M, Gonzalez-Cortijo L, Jolis L, Echarri MJ, Munoz M, Pascual T, Amigo Y, Casas M, Carrasco E, Casas A. Phase III study to evaluate patient's preference of subcutaneous versus intravenous trastuzumab in HER2-positive metastatic breast cancer patients: Results from the ChangHER study (GEICAM/2012-07). Eur J Cancer Care (Engl). 2020 Jul;29(4):e13253. doi: 10.1111/ecc.13253. Epub 2020 Jun 23.