The primary objective of this study is to assess the overall safety and tolerability of subcutaneous (SC) trastuzumab using SID (Singel Injection Device) in HER2-positive eBC (early Breast Cancer) patients self-administered at home under supervision…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective
The primary objective of this study is to assess the overall safety and
tolerability of subcutaneous (SC) trastuzumab using SID in HER2-positive eBC
patients self-administered at home under supervision of trained HCP.
Secondary outcome
Secondary Objectives
The secondary objectives of this study are PK analysis of self-administration
at home, patient reported outcomes and proportion of patients choosing to
return to hospital administration.
Exploratory Objective
To assess efficacy (disease-free survival and overall survival data)
Background summary
Breast cancer is the most commonly diagnosed cancer (23% of all cancers) and
the leading cause of cancer death in women worldwide. Studies have shown that
women whose tumours exhibit either amplification of the HER2 gene or
overexpression of its encoded protein have a more aggressive form of breast
cancer that is associated with significantly shortened disease-free (DFS) and
overall survival (OS) compared with women whose tumours do not over express
HER2. Trastuzumab (Herceptin) is a humanized monoclonal antibody directed
against the extracellular domain of HER2. It is indicated for the treatment of
patients with HER2-positive MBC and EBC and HER2-positive metastatic gastric
cancer. The efficacy and safety of intravenous (IV) trastuzumab have been well
characterized. Subcutaneous administration of trastuzumab takes significantly
less time (up to 5 minutes) compared to IV infusion (30 to 90 minutes) and this
is expected to improve treatment convenience and compliance. Trastuzumab SC is
een new route of administration and might provide the oppertunity of
administration of trastuzumab outside the hospital and optimize the ease, costs
and compliace for patients in the near future.
Study objective
The primary objective of this study is to assess the overall safety and
tolerability of subcutaneous (SC) trastuzumab using SID (Singel Injection
Device) in HER2-positive eBC (early Breast Cancer) patients self-administered
at home under supervision of trained HCP (health care professional).
Study design
The study is a single arm phase IIIb, open label, local multicenter study to
assess the safety and tolerability of trastuzumab solution injected
subcutaneously with a single injection device (SID) in patients with
Her2-positive eBC, following surgery and chemotherapy (neo-adjuvant or
adjuvant).
Patients will receive a fixed dose of 600 mg trastuzumab SC throughout the
study, administered 3-weekly for up to a total of 1 year trastuzumab, unless
disease recurrence, unacceptable toxicity or patient withdrawal necessitates
earlier treatment cessation. The first three study treatment administrations
will occur in a hospital setting, following administrations will occur at home
unless patient chooses to go back to hospital administration. This choice will
be offered to patients after three administrations at home.
Patients are asked to come to the hospital for the screening / baseline visit
and then for 5 visits during the treatment period, a safety follow-up visit 4
weeks after the last study treatment and every 6 months (up to 24 months after
the safety follow up visit)
Intervention
The investigational medicinal product for this study is trastuzumab SC 600 mg,
supplied as a SID formulation.
Patients in this local study will receive a fixed dose of 600 mg trastuzumab SC
throughout the study, administered 3-weekly up to a total of 18 cycles/1 year
trastuzumab, unless disease recurrence, unacceptable toxicity or study
withdrawal necessitates earlier treatment cessation.
Trastuzumab SC via SID will be administered at hospital by a HCP for first 3
cycles, patients will be trained for self-administration.
Trastuzumab SC via SID will be administered at home for the following cycles,
once adequately trained, patient are permitted to self-administer the injection
supervised by a HCP.
Concurrent curative radiotherapy or anti-hormone therapy will be allowed as per
institutional guidelines.
SID: a ready-to-use automated injection device containing 600 mg/5 ml
trastuzumab
Study burden and risks
The following study-specific actions are extra compared to the standard
treatment as stated in the SPC text for the transtuzumab treatment: Screening:
* Pregnancytest in blood (if the patient is a woman of childbearing potential).
This test should be performed within 7 days prior to the first treatment with
trastuzumab. Additional pregnancy tests (urine) should be preformed if
clinically indicated during the study treatment and for 7 months after the last
dose of study drug. Positive urine pregnancy tests should be confirmed by serum
pregnancy test.
* Registration of demographic information, medical history and (if needed)
medication.
* Assessment of cardiac function (including ECG)
* Withdrawal of about 20ml blood for standard laboratory tests.
* ECOG.
During the period of study treatment the patient will receive up to 18
treatments (for up to 12 months): every 3 weeks 1 trastuzumab treatment is
given unless the patient has unacceptable side effects or if the cancer is
recurrent (in which case the study treatment will be discontinued) .
The following actions will take place during the treatment period:
* Monitoring of vital signs with each administration.
* Cycle 1, 5, 9, 13 and/or the last treatment cycle: ECOG, weight, physical
examination, assessment of cardiac function, discussion of health status and
medication use.
* At 1st, 9th and last cycle, additional blood samples will be taken for
standard laboratory tests (approximately 20 ml)
* At cycle 1, 3, 9, 10 or 13, blood withdrawal to determine the amount of
trastuzumab in the blood (approximately 2 ml)
* At cycle 3 and 9 a questionnaire will be completed.
The following assessments will take place during the follow-up visits:
* Monitoring of vital signs, physical examination and determination of the
weight.
* ECOG.
* Evaluation of cardiac function (including ECG and ECHO or MUGA).
* Standard follow-up for breast cancer.
* Discussion of health, including possible side effects (adverse medical
events) that may have occurred since the last trastuzumab has been
administered.
* Discussion of medication.
* Collection of blood samples for standard laboratory tests.
* Every 6 months contact for health and well-being. This follow-up takes at
least up to 24 months.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
1. Female and male patients aged * 18 years
2. Eastern Cooperative Oncology Group (ECOG) performance status 0*1
3. Hormonal therapy will be allowed as per institutional guidelines
4. Prior use of anti-HER2 therapy in combination with chemotherapy will be allowed
5. Left ventricular ejection fraction (LVEF) of * 50% measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC, or, for those who were receiving trastuzumab when beginning the study, documented results within an acceptable limit from a cardiac assessment within 3 months prior to enrolment.Except in case patient received anthracycline treatment previously then documented results within an acceptable limit from a cardiac assessment within 14 days prior to enrolment.
6. HER2-positive disease immunohistochemistry (IHC)3+ or in situ hybridization (ISH) positive as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay
7. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast
8. No evidence of residual, locally recurrent or metastatic disease after completion of surgery and chemotherapy, or during concurrent chemotherapy (neo-adjuvant or adjuvant)
9. Use of concurrent curative radiotherapy will be permitted
10. Completion of surgery and chemotherapy (if applicable) for eBC
Exclusion criteria
1. History of other malignancy which could affect compliance with the protocol or interpretation of results.
2. Patients with severe dyspnea at rest or requiring supplementary oxygen therapy
3. Patients with other concurrent serious diseases that may interfere with planned treatment
4. Serious cardiac illness or medical conditions that would preclude the use of trastuzumab
5. Pregnant or lactating women.
6. Women of childbearing potential (premenopausal or less than 12 months of amenorrhea post-menopause, unless surgically sterile), and male patients with partners of childbearing potential who are unable or unwilling to use adequate contraceptive measures during study treatment. In this study, menopause is defined as a minimum of 12 consecutive months of amenorrhea during which time no other biological or physiological cause had been identified as a potential cause of this state. Examples of adequate contraceptive measures are intrauterine device, barrier method (condoms, diaphragm) also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not acceptable
7. Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment
8. Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin® including hyaluronidase, or the adhesive of the SC device, or a history of severe allergic or immunological reactions
9.Patients assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
10. Impaired hepatic function
11. Inadequate renal function
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000829-31-NL |
| CCMO | NL44120.056.13 |
| Other | wordt geregistreerd op www.clinicaltrials.gov |