Breast Cancer
Conditions
Keywords
Subcutaneous trastuzumab, Intravenous trastuzumab, HER2 positive, Advanced Breast Cancer
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.
Interventions
DRUGTrastuzumab Injectable Solution
Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles.
DRUGTrastuzumab Injectable Product
Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles
Powder for concentrate for solution for infusion. 1 cycle
Sponsors
Spanish Breast Cancer Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference | Up to 12 weeks | The percentage of patients who indicate a preference for the use of the intravenous vs subcutaneous administration of trastuzumab was analyzed with the answer to the questionnaire C2, question number 39 (All things considered, what method of administration do you prefer? Subcutaneous; Intravenous; No preference) of experiences and preferences of the patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | Up to 12 weeks | The percentage of patients who indicate a preference for the use of SC administration by vial or device was analyzed. This was discussed in the answer to questionaire C3, question number 28 (All things considered, what method of administration do you prefer? Subcutaneous; Intravenous; No preference) of the questionnaire of experiences and preferences of the patient. |
| Percentage of Medical Staff With Intravenous vs. Subcutaneous Preference | Up to 12 weeks | The medical staff satisfaction was analyzed with the answers to question number 33a (Considering all aspects, with what method of administration were you more satisfied? Between Intravenous vs. Subcutaneous: Intravenous; Subcutaneous; No differences) of the questionnaire of experiences and preferences of the medical staff. Health care professionals were not considered enrolled, but did contribute to this assessment. |
| Percentage of Medical Staff Subcutaneous Device vs. Vial Preference | Up to 12 weeks | The medical staff satisfaction was analyzed with the answers to question number 33b (Considering all aspects, with what method of administration were you more satisfied? Between Vial vs. Device: Preferred device; Preferred vial; No Preference) of the questionnaire of experiences and preferences of the medical staff. Health care professionals were not considered enrolled, but did contribute to this assessment. |
| Patient Time in Healthcare Unit and Sitting in Chair/Bed | An average of 4 months | Time spent by patient in the healthcare unit: Time between entrance and exit from the healthcare unit. Time spent by patient sitting in the infusion/treatment chair/bed: Time between sitting and rising from the patient treatment chair/bed The data was collected by qualified observers from site staff that measured the time spent by healthcare professional using a chronometer, and write it down in the paper questionnaires or directly or after in the electronic case report form. |
| The Number of Participants Who Experienced Adverse Events (AE) | Through study treatment, an average of 12 weeks | Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03. |
Countries
Spain
Participant flow
Recruitment details
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.
Pre-assignment details
This is not a cross-over study.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: T-IV + T-SC Vial + T-SC Device Trastuzumab intravenous (T-IV) x 1 cycle (usual dose of Trastuzumab), followed by 600mg of Trastuzumab Subcutaneous (T-SC) with vial (Injectable Solution) x 2 cycles, followed by 600mg of T-SC with single injection device (SID) x 2 cycles. | 81 |
| Arm B: T-IV + T-SC Device + T-SC Vial Trastuzumab intravenous (T-IV) x 1 cycle (usual dose of Trastuzumab), followed by 600mg of Trastuzumab Subcutaneous (T-SC) with single injection device (SID) x 2 cycles, followed by 600mg of T-SC with vial (Injectable Solution) x 2 cycles. | 85 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Not complete at least 2 questionaries | 4 | 2 |
| Overall Study | Not receive study treatment | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Arm B: T-IV + T-SC Device + T-SC Vial | Arm A: T-IV + T-SC Vial + T-SC Device |
|---|---|---|---|
| Administration route at registration Intramuscular | 10 Participants | 5 Participants | 5 Participants |
| Administration route at registration Intravenous | 52 Participants | 27 Participants | 25 Participants |
| Administration route at registration None | 41 Participants | 19 Participants | 22 Participants |
| Administration route at registration Oral | 54 Participants | 29 Participants | 25 Participants |
| Administration route at registration Subcutaneous | 9 Participants | 5 Participants | 4 Participants |
| Age, Continuous | 60 years | 58 years | 63 years |
| Bone metastases at registration No | 91 Participants | 44 Participants | 47 Participants |
| Bone metastases at registration Yes | 75 Participants | 41 Participants | 34 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG 0 | 124 Participants | 61 Participants | 63 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG 1 | 41 Participants | 24 Participants | 17 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG 2 | 1 Participants | 0 Participants | 1 Participants |
| Estrogen Receptor Negative | 60 Participants | 25 Participants | 35 Participants |
| Estrogen Receptor Positive | 106 Participants | 60 Participants | 46 Participants |
| Median of prior treatment lines at registration | 1 Treatment lines | 1 Treatment lines | 1 Treatment lines |
| Menopausal status Postmenopausal | 146 Participants | 73 Participants | 73 Participants |
| Menopausal status Premenopausal | 20 Participants | 12 Participants | 8 Participants |
| Metastases 1 at diagnosis No | 105 Participants | 52 Participants | 53 Participants |
| Metastases 1 at diagnosis Yes | 61 Participants | 33 Participants | 28 Participants |
| Other anti Human Epidermal growth factor Receptor 2 (HER-2) therapy at registration Lapatinib | 8 Participants | 5 Participants | 3 Participants |
| Other anti Human Epidermal growth factor Receptor 2 (HER-2) therapy at registration None | 139 Participants | 69 Participants | 70 Participants |
| Other anti Human Epidermal growth factor Receptor 2 (HER-2) therapy at registration Pertuzumab | 19 Participants | 11 Participants | 8 Participants |
| Prior treatment lines at registration 1 Line | 103 participants | 55 participants | 48 participants |
| Prior treatment lines at registration 2 Lines | 29 participants | 10 participants | 19 participants |
| Prior treatment lines at registration 3 Lines | 15 participants | 9 participants | 6 participants |
| Prior treatment lines at registration 4 Lines | 10 participants | 6 participants | 4 participants |
| Prior treatment lines at registration 5 Lines | 3 participants | 2 participants | 1 participants |
| Prior treatment lines at registration 6 Lines | 3 participants | 2 participants | 1 participants |
| Prior treatment lines at registration 7 Lines | 2 participants | 1 participants | 1 participants |
| Prior treatment lines at registration None Line | 1 participants | 0 participants | 1 participants |
| Progesterone Receptor Negative | 88 Participants | 38 Participants | 50 Participants |
| Progesterone Receptor Positive | 78 Participants | 47 Participants | 31 Participants |
| Race/Ethnicity, Customized Arabian | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 161 Participants | 83 Participants | 78 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 166 Participants | 85 Participants | 81 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Skin/soft tissue/lymph nodes metastases at registration No | 106 Participants | 56 Participants | 50 Participants |
| Skin/soft tissue/lymph nodes metastases at registration Yes | 60 Participants | 29 Participants | 31 Participants |
| Time with IV trastuzumab for metastasis at registration | 1.8 years | 1.78 years | 1.9 years |
| Treatment/s combined with IV-trastuzumab at registration Chemotherapy (CT) | 21 Participants | 9 Participants | 12 Participants |
| Treatment/s combined with IV-trastuzumab at registration Homonotherapy (HT) | 70 Participants | 36 Participants | 34 Participants |
| Treatment/s combined with IV-trastuzumab at registration None | 48 Participants | 24 Participants | 24 Participants |
| Treatment/s combined with IV-trastuzumab at registration Other anti-cancer therapy | 17 Participants | 10 Participants | 7 Participants |
| Treatment/s combined with IV-trastuzumab at registration Other anti-cancer therapy+CT | 6 Participants | 4 Participants | 2 Participants |
| Treatment/s combined with IV-trastuzumab at registration Other anti-cancer therapy+HT | 4 Participants | 2 Participants | 2 Participants |
| Visceral metastases at registration No | 76 Participants | 36 Participants | 40 Participants |
| Visceral metastases at registration Yes | 90 Participants | 49 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 85 |
| other Total, other adverse events | 76 / 81 | 84 / 85 |
| serious Total, serious adverse events | 2 / 81 | 10 / 85 |
Outcome results
Primary
Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference
The percentage of patients who indicate a preference for the use of the intravenous vs subcutaneous administration of trastuzumab was analyzed with the answer to the questionnaire C2, question number 39 (All things considered, what method of administration do you prefer? Subcutaneous; Intravenous; No preference) of experiences and preferences of the patient.
Time frame: Up to 12 weeks
Population: Patients were randomized 1:1 in 2 arms:~Arm A: (1 cycle IV-t followed by 2 cycles SC-t with vial followed by 2 cycles SC-t with SID) Arm B: (1 cycle IV-t followed by 2 cycles SC-t with SID followed by 2 cycles SC-t with vial)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference | Subcutaneous | 66 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference | Intravenous | 6 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference | No preference | 4 Participants |
| Arm B: T-IV + T-SC Device + T-SC Vial | Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference | Subcutaneous | 71 Participants |
| Arm B: T-IV + T-SC Device + T-SC Vial | Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference | Intravenous | 5 Participants |
| Arm B: T-IV + T-SC Device + T-SC Vial | Percentage of Participants With Subcutaneous vs. Intravenous Treatment Preference | No preference | 7 Participants |
Secondary
Patient Time in Healthcare Unit and Sitting in Chair/Bed
Time spent by patient in the healthcare unit: Time between entrance and exit from the healthcare unit. Time spent by patient sitting in the infusion/treatment chair/bed: Time between sitting and rising from the patient treatment chair/bed The data was collected by qualified observers from site staff that measured the time spent by healthcare professional using a chronometer, and write it down in the paper questionnaires or directly or after in the electronic case report form.
Time frame: An average of 4 months
Population: This analysis was considered from 87 patients of the 166 patients included into the study, on who information of observed tasks were collected. 217 observations were made from these patients: 74 about IV-t administration process, 75 about SC-SID administration process, 68 about SC-Vial administration process.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: T-IV + T-SC Vial + T-SC Device | Patient Time in Healthcare Unit and Sitting in Chair/Bed | Healthcare unit | 203 minutes | Standard Deviation 123.57 |
| Arm A: T-IV + T-SC Vial + T-SC Device | Patient Time in Healthcare Unit and Sitting in Chair/Bed | Sitting in the infusion/treatment chair/bed | 100.01 minutes | Standard Deviation 56.34 |
| Arm B: T-IV + T-SC Device + T-SC Vial | Patient Time in Healthcare Unit and Sitting in Chair/Bed | Healthcare unit | 144.84 minutes | Standard Deviation 121.99 |
| Arm B: T-IV + T-SC Device + T-SC Vial | Patient Time in Healthcare Unit and Sitting in Chair/Bed | Sitting in the infusion/treatment chair/bed | 31.6 minutes | Standard Deviation 28.74 |
| Boths Arms: Subcutaneous-Trastuzumab Device (SC-t SID) | Patient Time in Healthcare Unit and Sitting in Chair/Bed | Healthcare unit | 122.9 minutes | Standard Deviation 112.33 |
| Boths Arms: Subcutaneous-Trastuzumab Device (SC-t SID) | Patient Time in Healthcare Unit and Sitting in Chair/Bed | Sitting in the infusion/treatment chair/bed | 24.75 minutes | Standard Deviation 15.42 |
Secondary
Percentage of Medical Staff Subcutaneous Device vs. Vial Preference
The medical staff satisfaction was analyzed with the answers to question number 33b (Considering all aspects, with what method of administration were you more satisfied? Between Vial vs. Device: Preferred device; Preferred vial; No Preference) of the questionnaire of experiences and preferences of the medical staff. Health care professionals were not considered enrolled, but did contribute to this assessment.
Time frame: Up to 12 weeks
Population: Questionnaires were given to the health care professionals of both arms. Information has been analyzed per administration type, not per arm.~39 health care professional satisfaction questionnaires were completed. Health care professionals were not considered enrolled, but did contribute to this assessment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Medical Staff Subcutaneous Device vs. Vial Preference | Preferred device | 20 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Medical Staff Subcutaneous Device vs. Vial Preference | Preferred vial | 11 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Medical Staff Subcutaneous Device vs. Vial Preference | No Preference | 8 Participants |
Secondary
Percentage of Medical Staff With Intravenous vs. Subcutaneous Preference
The medical staff satisfaction was analyzed with the answers to question number 33a (Considering all aspects, with what method of administration were you more satisfied? Between Intravenous vs. Subcutaneous: Intravenous; Subcutaneous; No differences) of the questionnaire of experiences and preferences of the medical staff. Health care professionals were not considered enrolled, but did contribute to this assessment.
Time frame: Up to 12 weeks
Population: Questionnaires were given to the health care professionals of both arms. Information has been analyzed per administration type, not per arm.~39 health care professional satisfaction questionnaires were completed. Health care professionals were not considered enrolled, but did contribute to this assessment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Medical Staff With Intravenous vs. Subcutaneous Preference | Subcutaneous | 34 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Medical Staff With Intravenous vs. Subcutaneous Preference | Intravenous | 0 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Medical Staff With Intravenous vs. Subcutaneous Preference | No differences | 4 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Medical Staff With Intravenous vs. Subcutaneous Preference | Not answered | 1 Participants |
Secondary
Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference
The percentage of patients who indicate a preference for the use of SC administration by vial or device was analyzed. This was discussed in the answer to questionaire C3, question number 28 (All things considered, what method of administration do you prefer? Subcutaneous; Intravenous; No preference) of the questionnaire of experiences and preferences of the patient.
Time frame: Up to 12 weeks
Population: Patients were randomized 1:1 in 2 arms:~Arm A: (1 cycle IV-t followed by 2 cycles SC-t with vial followed by 2 cycles SC-t with SID) Arm B: (1 cycle IV-t followed by 2 cycles SC-t with SID followed by 2 cycles SC-t with vial) It has been analysed in patients from Intention To Treat (ITT) population which have completed questionnaire nº 3 (Arm A 72 patients and Arm B 80 patients).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | Vial | 20 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | Device | 46 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | No preference | 4 Participants |
| Arm A: T-IV + T-SC Vial + T-SC Device | Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | Not answered | 2 Participants |
| Arm B: T-IV + T-SC Device + T-SC Vial | Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | Not answered | 3 Participants |
| Arm B: T-IV + T-SC Device + T-SC Vial | Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | Vial | 20 Participants |
| Arm B: T-IV + T-SC Device + T-SC Vial | Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | No preference | 13 Participants |
| Arm B: T-IV + T-SC Device + T-SC Vial | Percentage of Participants With Subcutaneous Treatment (Vial vs Device Administration) Preference | Device | 44 Participants |
Secondary
The Number of Participants Who Experienced Adverse Events (AE)
Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03.
Time frame: Through study treatment, an average of 12 weeks
Population: Safety Population included all patients randomized in the study who received at least one dose of treatment, and they were analyzed according to the actual treatment received (81 patients in arm A and 85 patients in arm B).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: T-IV + T-SC Vial + T-SC Device | The Number of Participants Who Experienced Adverse Events (AE) | 76 Participants |
| Arm B: T-IV + T-SC Device + T-SC Vial | The Number of Participants Who Experienced Adverse Events (AE) | 84 Participants |