A randomized, 3 arm, multicentre, phase III study to evaluate the efficacy and the safety of T-DM1 combined with pertuzumab or T-DM1 combined with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab plus taxane, as first line treatment in HER2- positive progressive or recurrent locally advanced or metastatic breast cancer (MBC). - ND

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2009-017905-13-IT
• Date of registration: 16/07/2010
• Prospective Registration: No
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A randomized, 3 arm, multicentre, phase III study to evaluate the efficacy and the safety of T-DM1 combined with pertuzumab or T-DM1 combined with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab plus taxane, as first line treatment in HER2- positive progressive or recurrent locally advanced or metastatic breast cancer (MBC). - ND
• Scientific title: A randomized, 3 arm, multicentre, phase III study to evaluate the efficacy and the safety of T-DM1 combined with pertuzumab or T-DM1 combined with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab plus taxane, as first line treatment in HER2- positive progressive or recurrent locally advanced or metastatic breast cancer (MBC). - ND
• Date of first enrolment: 06/07/2010
• Target sample size: 1092
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017905-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
a) Disease specific inclusion criteria: 1. HER2-positive breast cancer as defined by IHC 3+ and /or ISH positive, prospectively confirmed by a Sponsor designated central laboratory prior to enrollment. Archival tumor samples obtained from primary or metastatic sites are acceptable. 2. Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and be a candidate for chemotherapy. Patients with locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent.Patients with standard curative options available to them will be excluded from the trial. 3. Patients may have measurable and/or non-measurable disease which must be evaluable per RECIST 1.1. b) General inclusion criteria: 4. Signed written informed consent approved by the institution’s Independent Ethical Committee (IEC). 5. Age = 18 years. 6. ECOG Performance Status 0 or 1. 7. Adequate organ function as determined by the following laboratory results, within approximately 14 days prior to randomization: • Absolute neutrophil count > 1500 cells/mm3 • Platelet count > 100,000 cells/mm3 • Hemoglobin > 9.0 g/dL; patients may receive red blood cell transfusions to obtain this level • Total bilirubin = 1.5x upper limit of normal (ULN) unless the patient has documented Gilbert’s syndrome • SGOT (AST), SGPT (ALT), and alkaline phosphatase = 2.5 x ULN, except for patients with bone metastases: alkaline phosphatase = 5 x ULN • Serum creatinine = 1.5x upper limit of normal (ULN) • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) < 1.5 x ULN (unless on therapeutic anti-coagulation) 8. For women of childbearing potential and men with partners of childbearing potential, agreement to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner and to continue its use for the duration of study treatment and for 6 months after the last dose of study treatment. Male patients whose partners are pregnant must use condoms for the duration of the study treatment and for 6 months after the last dose of study treatment. Specific country and/or local requirements for contraception will be followed. 9. A negative pregnancy test must be available for premenopausal women and for women less than 12 months after the onset of menopause.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Disease related Exclusion Criteria:
History of systemic anti-cancer therapy after the diagnosis of
MBC cancer.
1. An interval of < 6 months from the last dose of vincaalkaloid or taxane cytotoxic chemotherapy in the neoadjuvant or adjuvant setting until the time of metastatic diagnosis.
2. Hormone therapy < 7 days prior to randomization.
3. Trastuzumab (neoadjuvant/adjuvant setting) < 21 days prior to randomization.
4. Prior T-DM1 or pertuzumab therapy.
5. Treatment with any anti-cancer investigational drug within
28 days prior to commencing study treatment.
6. History of other malignancy within the last 5 years except for
appropriately treated carcinoma in situ of the cervix, nonmelanoma
skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome.
7. Brain metastases that are either untreated, progressive or require any type of therapy (e.g., radiation, surgery, or steroids) to control symptoms from brain metastases within
60 days prior to the first study treatment dose.
8. Radiotherapy for the treatment of locally advanced disease or for metastatic sites of disease performed within 14 days prior to study enrollment, and/or radiation of > 30% of marrowbearing bone.
9. Symptomatic hypercalcemia requiring use of bisphosphonate therapy within 21 days prior to the first study treatment. Patients who receive bisphosphonate therapy specifically to
prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
10. Current peripheral neuropathy Grade = 2 per NCI-CTCAE version 4.0.
11. History of exposure to the following cumulative doses of anthracyclines as specified below.
o Doxorubicin > 500 mg/m2 o Liposomal doxorubicin > 900 mg/m2 o Epirubucin > 720 mg/m2 o Mitoxantrone > 120 mg/m2
o Idarubicin > 90 mg/m2 If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.
13. Cardiopulmonary dysfunction as defined by: - Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic > 100 mm Hg)
- Inadequately controlled angina or serious cardiac arrhythmia not controlled by adequate medication
o Inadequate left ventricular ejection function (LVEF) at baseline, as defined as LVEF <50% by either
echocardiogram or MUGA o History of symptomatic congestive heart failure (CHF – Grade = 3 per NCI CTCAE version 4.0 or Class = II New York Health Association (NYHA criteria o History of a decrease in LVEF to <40% or symptomatic CHF with prior trastuzumab treatment o Myocardial infarction within 6 months prior to randomization
o Current dyspnoea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
General exclusion criteria:
14. Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary or metabolic disease; wound healing disorders; ulcers; bone fractures).
15. Current pregnancy and lactation.
16. Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment. Et al.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients who have HER2 -positive (IHC 3+ and /or ISH+) progressive or recurrent locally advanced or previously untreated metastatic breast cancer.
MedDRA version: 9.1 Level: LLT Classification code 10027475
MedDRA version: 9.1 Level: LLT Classification code 10065430
MedDRA version: 9.1 Level: LLT Classification code 10006198

Intervention(s)

Product Name: T-DM1
Product Code: Ro 530-4020
Pharmaceutical Form: Powder for infusion*
CAS Number: 1018448-65-1
Current Sponsor code: Ro 530-4020
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-

Trade Name: Herceptin
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Trastuzumab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Name: Pertuzumab
Product Code: Ro 436-8451/F01
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 380610-27-5
Current Sponsor code: Ro 436-8451
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 420-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: Docetaxel
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Pharmaceutical Form: Powder and solvent for solution for infusion
INN or P

Primary Outcome(s)

Primary end point(s): • Progression Free Survival (PFS): to compare the efficacy of he combination of T-DM1 plus pertuzumab and/or
T-DM1 plus pertuzumab-placebo versus trastuzumab plus
docetaxel/paclitaxel in patients with HER2 positive progressive or recurrent locally advanced breast cancer or
previously untreated metastatic breast cancer patients, based on tumor assessments reviewed by an independent
review facility (IRF).
• To compare the safety of the combination of T-DM1 plus pertuzumab and T-DM1 plus pertuzumab-placebo
versus trastuzumab plus docetaxel or paclitaxel in the
aforementioned patient population.

Secondary Objective: The secondary objectives for this study are to compare the combination of T-DM1 plus pertuzumab and T-DM1 plus pertuzumab-placebo versus trastuzumab plus docetaxel/paclitaxel with respect to the following parameters: - Overall Response Rate (ORR) by IRF assessment - Overall Survival Rate (OS) - 1-year Survival Rate - PFS and ORR based on investigator tumor assessment - Clinical Benefit Rate (CBR: CR+PR + [SD = 6 months]) based on IRF and investigator tumor assessment - Time to Treatment Failure (TTF) by IRF assessment - Duration of Response (DR) based on IRF assessment - Safety and tolerability based on the frequency of grade 3 /4 AEs, ICU visits, SAEs and adverse events of special interest - Quality of Life (QoL), Productivity and Health Resource - Et al.

Main Objective: • Progression Free Survival (PFS): to compare the efficacy of the combination of T-DM1 plus pertuzumab and/or T-DM1 plus pertuzumab-placebo versus trastuzumab plus docetaxel/paclitaxel in patients with HER2 positive progressive or recurrent locally advanced breast cancer or previously untreated metastatic breast cancer patients, based on tumor assessments reviewed by an independent review facility (IRF). • To compare the safety of the combination of T-DM1 plus pertuzumab and T-DM1 plus pertuzumab-placebo versus trastuzumab plus docetaxel or paclitaxel in the aforementioned patient population.

Secondary ID(s)

BO22589

2009-017905-13-AT

Ethics review

Status: Approved
Approval date: 06/07/2010
Contact:

Results

• Results available: Yes
• Date Posted: 07/01/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017905-13/results