A clinical trial for patients with breast cancer

• Register: EUCTR
• Last refreshed on: 29 August 2016
• Main ID: EUCTR2013-004679-11-HU
• Date of registration: 17/06/2014
• Prospective Registration: No
• Primary sponsor: Pfizer Inc
• Public title: A clinical trial for patients with breast cancer
• Scientific title: A Randomized, Double-blind Pharmacokinetic Study of PF-05280014 Plus Taxotere and Carboplatin Versus Herceptin Plus Taxotere And Carboplatin For The Neoadjuvant Treatment Of Patients With Operable HER2-Positive Breast Cancer - REFLECTION B327-04
• Date of first enrolment: 16/06/2014
• Target sample size: 220
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004679-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Herceptin Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Czech Republic, Hungary, Italy, Poland, Russian Federation, Serbia, Slovakia, Ukraine, United States

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female patients aged 18 years or older.
2. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study.
3. Histologically confirmed HER2 overexpressing invasive breast cancer.
4. Plan for definitive surgical resection of breast tumor (ie, lumpectomy or mastectomy, and sentinel node (SN) biopsy or axillary lymph node dissection (ALND).
5. Plan for neoadjuvant chemotherapy.
6. Documentation of HER2 gene amplification or overexpression by one of the following: •Gene amplification by fluorescent in-situ hybridization (FISH) chromogenic in-situ hybridization (CISH); or dual in-situ hybridization (DISH) (as defined by the manufacturer's kit instruction); OR •Overexpression by immunohistochemistry (IHC) categorized as IHC3+; OR •Overexpression by immunohistochemistry categorized as IHC2+ with FISH, CISH, or DISH confirmation. Determination of HER2 positive status using one of the Sponsor approved analytical test methods listed in the Case Record Form If HER2 status is unavailable or was determined using a test other than a Sponsor-approved assay listed in Appendix 1 of the Protocol, eligibility must be documented prior to randomization: a. Confirmed by the Sponsor-provided central laboratory;b. HER2 local testing using both an IHC and an in-situ hybridization analytical test neither of which are considered Sponsor approved. The results from both assays must be unequivocal (ie, IHC result must be categorized as IHC3+).7. Measurable disease in the breast after diagnostic biopsy, defined as longest diameter = 2.0 cm.
8. Known Estrogen Receptor (ER) and Progesterone Receptor (PR) hormone status at study entry.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. Left ventricular ejection fraction (LVEF) of = 55% by 2D echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA).
11. Normal bone marrow function as defined by:
•absolute neutrophil count (ANC) > 1.5 x 109 g/dL (1,500/µL);
•platelets > 100 x 109 g/dL (100,000/µL);
•hemoglobin > 10.0 g/dL.
12. Normal hepatic function as defined by:
•total bilirubin = 1.5 x upper limit of normal (ULN) (<3 ULN if Gilberts disease);
•aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 2.5 x upper limit of normal (ULN) (= 5x ULN if liver metastases are present).
13. Patients with an elevated unconjugated bilirubin (Gilbert's syndrome) will be eligible if hepatic enzymes and function are otherwise within normal limits (ie, AST, ALT, and Alkaline Phosphatase are within normal limits), and there is no evidence of hemolysis.
14. Serum creatinine = 1.5 × ULN or estimated creatinine clearance (CrCl) = 50 mL/min calculated by the Cockcroft-Gault.
15. Patients of childbearing potential must agree to use a highly effective methods of contraception as described in Section 4.4 Life Style Guidelines of the Protocol, throughout the study and for 12 months after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active.
16. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

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
Exclusion criteria:
1. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.
2. Bilateral breast cancer.
3. Inflammatory breast cancer.
4. Presence of known distant metastases (determined by principal investigator).
5. Received prior treatment, including chemotherapy, endocrine therapy, biologic therapy, radiation or surgery with the exception of diagnostic biopsy for primary breast cancer.
6. Other concomitant active malignancy or history of malignancy in the past 5 years except treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
7. Pre-existing clinically significant (= grade 2) peripheral neuropathy.
8. Any history of documented or current congestive heart failure, current high-risk uncontrolled arrhythmias, current angina pectoris requiring a medicinal product, current clinically significant valvular disease, current evidence of transmural infarction on electrocardiogram (ECG), or current poorly controlled hypertension.
9. Severe dyspnea at rest requiring supplementary oxygen therapy.
10. Known or demonstrated viral infection as listed below. Testing to demonstrate eligibility is required only in countries where regulations mandate testing. In all other countries, testing should be considered if a patient is at risk for having undiagnosed infection (for
example due to history of injection drug use or due to geographic location).
a.Seropositivity for human immunodeficiency virus (HIV);
b.Hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen [HbsAg] or antibody to hepatitis C virus [anti HCV] with confirmatory testing).
11. Recent infection requiring a course of systemic anti-infectives that were completed = 14 days before enrollment (with the exception of uncomplicated urinary tract infection).
12. Participation in other studies involving investigational drug(s) (Phases 1-4) within = 4 weeks before randomization and/or during study participation. Patients participating in observational studies not involving an investigational drug(s) and/or long-term follow up of studies involving an investigational drug(s) in which treatment was completed 4 weeks before randomization are not excluded.
13. History of severe hypersensitivity reaction to platinum-coordination compounds, taxanes, trastuzumab, murine proteins, or excipients in their formulations.
14. Clinical contraindication to treatment with steroids preventing use as part of Taxotere® premedication.
15. Pregnant females; breastfeeding females; females of childbearing potential who are unwilling or unable to use two highly effective methods of contraception as outlined in this protocol for the duration of the study and for 12 months after last dose of investigational product.
16. History of another cancer diagnosis (including contralateral breast cancer) within 5 years prior to screening for this study, with the exception of adequately treated ductal carcinoma in situ, cervical carcinoma in situ, or basal or squamous cell skin cancer.
17. Other severe acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product admi

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

Health Condition(s) or Problem(s) studied

HER2-Positive Breast Cancer (Early Stage)
MedDRA version: 17.1 Level: LLT Classification code 10006194 Term: Breast cancer NOS stage I System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Trastuzumab-Pfizer
Product Code: PF-05280014
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Herceptin®
Product Name: Herceptin®
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: trastuzumab-EI
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): Percent of patients with Cycle 5 Ctrough (Cycle 6 pre-dose) >20 µg/mL.

Main Objective: To compare the percentage of patients with steady state (Cycle 5) Ctrough >20 µg/mL between trastuzumab-Pfizer versus Herceptin® in patients with operable HER2-positive breast cancer who receive therapy together with Taxotere® and carboplatin in the neoadjuvant setting.

Secondary Objective: •To evaluate measures of tumor control for trastuzumab-Pfizer versus Herceptin®, when administered with combination with Taxotere® and carboplatin in the neoadjuvant setting;
•To evaluate the safety of trastuzumab-Pfizer versus Herceptin®, administered in combination with Taxotere® and carboplatin;
•To evaluate the immunogenicity of trastuzumab-Pfizer versus Herceptin®;
•To evaluate the Pharmacokinetics (PK) of trastuzumab-Pfizer and Herceptin®;
•To explore the relationship between drug exposure and pathologic complete response (pCR) for trastuzumab-Pfizer versus Herceptin®, administered in combination with Taxotere® and carboplatin.

Timepoint(s) of evaluation of this end point: Cycle 6 pre-dose - day 105

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See study flow chart pgs. 8-10 of the protocol

Secondary end point(s): - Pathologic Complete Response (pCR) defined as the absence of invasive neoplastic cells in the breast and lymph nodes.
- Safety characterized by type, incidence, severity, timing, seriousness, and relationship to study therapy of adverse events and laboratory abnormalities.
- Incidence of anti-trastuzumab antibodies (ADA), including neutralizing antibodies (NAb).
- Trough trastuzumab-Pfizer and Herceptin® (trastuzumab-EU) concentrations at selected cycles. - Objective Response Rate (ORR) defined as the percentage of subjects having Complete or Partial Response at EOT, based on radiographic assessments of the tumor.

Secondary ID(s)

B3271004

2013-004679-11-IT

Source(s) of Monetary Support

Pfizer Inc, 235 East 42nd Street, New York, NY 10017