Phase II Study With Trastuzumab + Paclitaxel in Locally Advanced HER2+ Tumors or Epirubicin + Taxotere in HER2- Tumors

December 1, 2014 updated by: Centro di Riferimento Oncologico - Aviano

Antitumor Immune Responses in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: a Phase II Study With Trastuzumab and Concomitant Weekly Paclitaxel in Patients With HER2+ Tumors or Epirubicin + Taxotere in HER2- Tumors.

Prospective, monoinstitutional, phase II study. Patients with HER 2 positive locally advanced breast cancer will be treated with 3 initial cycles (12 weeks) of trastuzumab plus paclitaxel and then if responding further 12 weeks and then with surgical resection, patients with HER2 negative breast carcinoma will be treated with 4 cycles (12 weeks) of epirubicin and taxotere. If responding 4 more cycles (12 weeks). Patients progressing will be treated depending on physician's and patient's preference

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Primary Objective: to determine the pathological complete response (pCR) and correlation with immune response.

Secondary Objectives:

  • to determine the progression free survival (PFS) and overall survival (OS);
  • to evaluate the safety of the treatment with particular attention to cardiac safety.

Inclusion Criteria:

  • Histologically proven breast carcinoma evaluated for HER 2 status and immune status
  • Locally advanced carcinoma (UICC stage II-III)
  • Age < 70 years
  • measurable lesions
  • ECOG Performance Status 0-2
  • Life expectancy > 3 months
  • Adequate bone marrow and hepatic functions
  • Creatinine Clearance > 40 ml/min
  • Written informed consent
  • Patients must be accessible for treatment and follow up

Exclusion criteria:

  • Prior chemotherapy or hormonal treatments
  • Brain metastases.
  • Past or current history of neoplasm other than curatively treated.
  • Concurrent treatment with other experimental drugs.
  • Left Ventricular Ejection Fraction (LVEF) <50 %
  • History of significant neurological or psychiatric disorders.

Treatment HER2 positive (defined as 3+ at Herceptest or FISH/CISH positive) Herceptin 4mg/kg first time, then 2 mg/kg weekly with concomitant paclitaxel 80 mg/mq weekly (one cycle corresponding to 4 weeks) for 12 weeks (3 cycles). Clinical and instrumental evaluation, in responding patients continue for additional 12 weeks (total 6 cycles), then surgical excision

HER2 negative:

Epirubicin 90 mg/mq and docetaxel 75 mg/mq every 3 weeks for 4 cycles. Clinical and instrumental evaluation, in responding patients continue for additional 12 weeks (total 8 cycles), then surgical excision.

Main Parameters of Activity:

  • Complete Remission (CR): complete disappearance of all previously detectable disease for a period of at least 28 days, and no new lesions.
  • Partial Remission (PR): more than 30% reduction in the longest diameter of target lesions, and no new lesions.
  • Stable Disease (SD): less than 30% reduction and less than 20% increase in the longest diameter of target lesions and no new lesions.
  • Progressive Disease (PD): an increase in size of more than 20% of at least one lesion of previously documented disease. Or the appearance of disease at any site.
  • Progression Free Survival (PFS) will be measured from the first day of the treatment until the first observation of disease progression or death due to any cause or the last date the patient was known to be progression free and alive.
  • Overall Survival (OS) will be computed as the time between the first day of treatment and the date of death or the last date the patient was known to be alive.

Main Parameters of Safety:

  • Adverse events, laboratory parameters.
  • All toxicity will be graded using the NCI common toxicity criteria (Appendix II). Cardiac events (CHF) will be graded according to NYHA

Study procedure:

  • At Baseline:
  • Complete medical history, ECOG PS, physical examination (including a neurological examination, height, weight,),
  • ECG
  • Left ventricular ejection fraction evaluation (LVEF, evaluated by echocardiography).
  • Blood chemistry (fasting blood sugar, transaminases, serum alkaline phosphatase, total bilirubin, total protein, albumin, creatinine, PT, fìbrinogen)
  • Complete blood count and differential
  • Calculated Creatinine Clearance/24 h
  • Chest X- ray
  • Abdomen computer tomography (CT) or ultrasound
  • Bone scan and X-ray (if appropriate)
  • Written informed consent.
  • During Treatment - Every Cycle:
  • Blood chemistry
  • Complete blood count and differential
  • Toxicity evaluation
  • Physical examination
  • During Treatment - Every 12 weeks (3-4 cycles):
  • Breast ultrasound
  • Surgical and medical evaluation
  • Left ventricular ejection fraction evaluation (LVEF) evaluated by echocardiography
  • ECOG PS
  • Before surgery:
  • Mammography, Ultrasound and Magnetic resonance
  • Long term Follow up - Every 3 months for the first 2 years, every 6 months years 3-5 then yearly
  • Survival

Statistical Considerations:

The aim of this phase II clinical trial is to detect 20% improvement in the pCR (i.e., from 25% to 54%). Simon's methods will be used to calculate sample size. Accrual of 46 patients has been planned considering a 80% of power to detect a 20% difference (two-sided type I error =0.05). The Chi-square test and Fisher's exact test will be used for qualitative parameters.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
46

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Pordenone
      • Aviano, Pordenone, Italy, 33081
        • Centro di Riferimento Oncologico

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologically proven breast carcinoma evaluated for HER 2 status and immune status
  • Locally advanced carcinoma (UICC stage II-III)
  • Age < 70 years
  • measurable lesions
  • ECOG Performance Status 0-2
  • Life expectancy > 3 months
  • Adequate bone marrow and hepatic functions
  • Creatinine Clearance > 40 ml/min
  • Written informed consent
  • Patients must be accessible for treatment and follow up.

Exclusion Criteria:

  • Prior chemotherapy or hormonal treatments
  • Brain metastases.
  • Past or current history of neoplasm other than curatively treated.
  • Concurrent treatment with other experimental drugs.
  • Left Ventricular Ejection Fraction (LVEF) <50 %
  • History of significant neurological or psychiatric disorders.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Locally advanced HER2+ breast cancer pts

HER2 positive (defined as 3+ at Herceptest or FISH/CISH positive):

treatment with Trastuzumab 4mg/kg first time, then 2 mg/kg weekly with concomitant paclitaxel 80 mg/mq weekly (one cycle corresponding to 4 weeks) for 12 weeks (3 cycles). Clinical and instrumental evaluation, in responding patients continue for additional 12 weeks (total 6 cycles), then surgical excision
Drug: Paclitaxel
Drug: Trastuzumab
Experimental: Locally advanced HER2- breast cancer pts

HER2 negative:

treatment with Epirubicin 90 mg/mq and docetaxel 75 mg/mq every 3 weeks for 4 cycles. Clinical and instrumental evaluation, in responding patients continue for additional 12 weeks (total 8 cycles), then surgical excision.
Drug: Docetaxel
Drug: Epirubicin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathological complete response (pCR)
Time Frame: 60 months
pCR was defined as no evidence of microscopic residual invasive cancer, both in breast and ipsilateral axillary lymph nodes, or residual carcinoma in situ in the absence of invasive breast cancer
60 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 60 months
From the first day of treatment to progression or death due to any cause or last contact patient was to be known progression free or alive
60 months
Overall survival
Time Frame: 60 months
Time between the date of first day of treatment and the date of death from any cause or the last date the patient was known to be alive.
60 months
Cardiac safety
Time Frame: 60 months
Number of patients with adverse cardiac events. The intensity of clinical adverse events will be graded according to the NCI Common Toxicity Criteria grading system in the toxicity categories that have recommended gradings
60 months
Host immune response
Time Frame: 60 months
Multiple parameters were investigated: T-cell responses against 13 immunogenic HLA-A*0201-restricted nonamer (9-mer) peptides; Immune cells subsets (CD3+ T cells, CD19+ B cells, CD3-CD16+CD56+ NK cells, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3+CD4+CD25+CD127-/lowFoxP3+ Treg cells, CD3+CD4+IL17+ Th17 cells. Among CD3+CD4+ and CD3+CD8+ T cells, CCR7+CD45RA+ naïve T cells , CCR7+CD45RA- Central Memory T cells, CCR7-CD45RA- Effector Memory T cells , CCR7-CD45RA+ Terminally Differentiated T cells, trastuzumab-dependent ADCC in the HER-2+ arm. Measure of immunologic parameters: changes from baseline recorded at 12 and 24 weeks of treatment
60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centro di Riferimento Oncologico - Aviano

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Riccardo Dolcetti, MD, Centro di Riferimento Oncologico - Aviano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 26, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 4, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 4, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CRO-18-2006

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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