Phase II, multicenter, open-label, clinical trial of Trabectedin (Yondelis®) in Metastatic Breast Cancer Patients with triple negative profile (ER-, PR-, HER2-), HER2 overexpressing tumors and BRCA1 or BRCA2 mutation carriers

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-000794-31-PL
• Date of registration: 16/11/2007
• Prospective Registration: Yes
• Primary sponsor: Pharma Mar, S.A.
• Public title: Phase II, multicenter, open-label, clinical trial of Trabectedin (Yondelis®) in Metastatic Breast Cancer Patients with triple negative profile (ER-, PR-, HER2-), HER2 overexpressing tumors and BRCA1 or BRCA2 mutation carriers
• Scientific title: Phase II, multicenter, open-label, clinical trial of Trabectedin (Yondelis®) in Metastatic Breast Cancer Patients with triple negative profile (ER-, PR-, HER2-), HER2 overexpressing tumors and BRCA1 or BRCA2 mutation carriers
• Date of first enrolment: 29/01/2008
• Target sample size: 321
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000794-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

France, Italy, Poland

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient´s written informed consent before any clinical trial-specific procedure.

2. Woman 18 years-of-age or older.
3. Histologically proven diagnosis of progressive metastatic breast cancer either in
documented:

• Group A: triple negative phenotype [Estrogen Receptor, Progesterone Receptor
and HER-2 negative status (surrogate of basal-like type)]. Patients will
be eligible if they had received prior therapy with an anthracycline and taxanes, including adjuvant or neoadjuvant therapy, but no more than three
prior chemotherapy regimens for metastatic disease. NOTE: re-treatment with
the same regimen or its components after a progression-free interval of 6 months
or longer will be considered a second regimen. This arm is closed for recruitment.

• Group B: HER-2 overexpressing breast cancer. Patients will be eligible if they
have progressive metastatic disease following treatment with trastuzumab-based
regimens or other HER-2 targeted therapy containing regimens, but no more than three prior regimens that contain HER-2 directed therapy and chemotherapy for metastatic disease are allowed. NOTE: re-treatment with the same regimen or its components after a progression-free interval of 6 months or longer will be considered as second regimen.

• Group C: Familial BRCA1 or BRCA2 mutation carriers. Patients will be eligible if
they have developed progressive metastatic disease after at least one prior
chemotherapy regimen in the adjuvant or metastatic setting. There is no limit to the
maximal number of prior therapies allowed

4. Measurable disease as defined by the radiological (CT-scan and MRI) Response
Evaluation Criteria in Solid Tumors (RECIST) Guidelines. If the only indicator lesion
is in a previously irradiated area, the recurrence must be biopsy proven.

5. Patients with bone metastases currently receiving biphosphonates for palliation
will be eligible if other sites of measurable disease are present.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

7. Hematologic variables:
• Hemoglobin =9 g/dL
• Absolute neutrophil count (ANC) =1,500/µL, and
• Platelet count =100,000/µL.

8. Serum creatinine = 1.5 mg/dL or creatinine clearance = 30 mL/min

9. Creatinine phosphokinase (CPK) = 2.5 ULN.

10. Hepatic function variables
• Total bilirubin = ULN.
• Total alkaline phosphatase = 2.5 ULN, or if > 2.5 ULN consider alkaline
phosphatase liver fraction or GGT or 5’ nucleotidase must be = ULN, if the
elevation could be osseous in origin.
• AST (serum aspartate transaminase [SGOT]) and ALT (serum alanine
transaminase [SGPT]) must be =2.5 x ULN.

11. Albumin = 25 g/l.

12. Complete recovered from the acute toxicity of any prior treatment. The presence
of alopecia or NCI-CTC grade 1 symptomatic peripheral neuropathy is allowed.

13. Patients may have CNS metastases if stable (no evidence of progression) for at
least 3 months after local therapy.
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:
1. Prior exposure to trabectedin.

2. Known hypersensitivity to any of the components of the trabectedin i.v.
formulation or dexamethasone.

3. More than three prior chemotherapy regimens for metastatic disease for group A
and B. NOTE:re-treatment with the same regimen or its components after a
progression-free interval of 6 months or more is considered a second regimen.

4. Pregnant or lactating women or any women of childbearing potential who is not
employing adequate contraception. Acceptable methods of contraception include;
IUD, and double barrier (condom with a contraceptive sponge or contraceptive
suppository). Use of hormonal contraception is not acceptable during this clinical
trial.

5. Completion of prior therapy: less than 2 weeks from radiation therapy (radiated
lesions may not serve as measurable disease) or last dose of hormonal therapy, less
than 3 weeks from prior chemotherapy or biological therapy (all acute toxicities must
be adequately recovered as per inclusion criteria # 12), less than 4 weeks with any
investigational agent.

6. History of another neoplastic disease (except basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ adequately treated) unless in remission for 5 years or longer.Group C patients can be enrolled with less than 5 years remission from another neoplastic disease; however, appropriate biopsy confirming current metastasic breast cancer is mandatory.

7. Patients with known leptomeningeal disease.

8. Other serious illnesses, such as:
• Congestive heart failure or angina pectoris; myocardial infarction within 1 year
before enrollment; uncontrolled arterial hypertension or arrhythmias
• Psychiatric disorder that prevents compliance with protocol
• Active viral hepatitis; or chronic liver disease
• Active infection
• Any other unstable medical conditions

9. Patients with a life expectancy < 3 months.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Progressive metastatic breast cancer previously treated in the following subpopulation of patients: Group A: Triple negative phenotype: Estrogen Receptor, Progesterone Receptor and HER-2 negative status (surrogate of basal-like type) Group B: HER-2 overexpressing tumors. Group C: Familial BRCA1 or BRCA2 mutation carriers
MedDRA version: 9.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic

Intervention(s)

Trade Name: YONDELIS®
Product Name: YONDELIS® (Trabectedin)
Product Code: ET-743
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: trabectedin
CAS Number: 114899-77-3
Current Sponsor code: ET-743
Other descriptive name: Ecteinascidin 743
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.-25

Trade Name: YONDELIS®
Product Name: YONDELIS® (Trabectedin)
Product Code: ET-743
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: trabectedin
CAS Number: 114899-77-3
Current Sponsor code: ET-743
Other descriptive name: Ecteinascidin 743
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.-0

Primary Outcome(s)

Main Objective: Primary Objective: to determine the objective response rate by RECIST (Complete and Partial Response [CR + PR]) with trabectedin in patients with the following metastatic
breast cancer subtypes:
Group A: triple negative profile (ER-,PR-,HER-2-)
Group B: human epidermal growth factor receptor-2 overexpressing tumors (HER-2+)
Group C: familial BRCA1 or BRCA2 mutation carriers

Secondary Objective: To assess in each group:
• Duration of response
• Progression-free survival
• Exploratory evaluation of changes in tumor volume (three dimensional
analysis) and changes in tumoral radiological density
• Safety profile in this patient population
• Exploratory, hypothesis-generating pharmacogenomic analyses to correlate
molecular parameters in patient samples with clinical outcomes (objective
response and PFS) within and across patient strata.

Primary end point(s): Confirmed objective tumor response (CR or PR) rate (RECIST) in each group.
Each patient will be assigned one of the following categories:
Complete response (CR)
Partial response (PR)
Stable disease (SD)
Progressive disease (PD)

Reasons for non-evaluability will be subdivided into the following categories:
1) ‘early toxicity’ (as reason for withdrawal without on-/end-oftreatment
tumor assessment available)
2) ‘never treated’ (no on-/end-of-treatment tumor assessment available)
3) ‘other’ (e.g., no baseline tumor assessment, technical
reasons, absence of on-/end-of-treatment tumor assessment for other reasons than ‘death’, ‘early toxicity’ or ‘never treated’, consent withdrawal before evaluation,)

To be assigned a status of PR or CR, changes in tumor measurements must be
confirmed by repeated assessments that should be performed no less than 4 weeks after the criteria for response are first met.

Secondary ID(s)

2007-000794-31-FR

ET-B-027-06