Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Disseminated Tumor Cells

NCT01779050 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201309084
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the efficacy of trastuzumab treatment in breast cancer patients with stage II-III human epidermal growth factor receptor 2 (HER2)-negative tumors and HER2-expressing bone marrow disseminated tumor cells (DTCs). Administering targeted trastuzumab therapy to these patients may result in the elimination of HER2 expressing disseminated tumor cells and improved disease free survival.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Disease Recurrence

  -Disease recurrence is defined as the documented appearance of local (breast, chest wall, axillary, supraclavicular nodes) or distant disease.

  Up to 3 years after completion of treatment (estimated to be 4 years)

• Death Rate

  Up to 3 years after completion of treatment (estimated to be 4 years)

Secondary Outcomes (1)

• Elimination of ERBB2 Overexpressing Bone Marrow DTCs

  Before treatment and after treatment (estimated to be 6-18 months)

Study Arms (2)

Arm I (definitive therapy)

ACTIVE COMPARATOR

Patients receive definitive surgery and best practice standard chemotherapy according to NCCN guidelines. The 5 chemo backbone options are: * doxorubicin or epirubicin plus cyclophosphamide followed by paclitaxel or docetaxel * docetaxel plus cyclophosphamide * single-agent paclitaxel * docetaxel plus carboplatin * fluorouracil plus epirubicin plus cyclophosphamide followed by paclitaxel or docetaxel

Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Epirubicin; Drug: Docetaxel; Drug: Fluorouracil

Arm II (definitive therapy, trastuzumab)

EXPERIMENTAL

Patients receive definitive surgery and best practice standard chemotherapy according to NCCN guidelines. The 5 chemo backbone options are: * doxorubicin or epirubicin plus cyclophosphamide followed by paclitaxel or docetaxel * docetaxel plus cyclophosphamide * single-agent paclitaxel * docetaxel plus carboplatin * fluorouracil plus epirubicin plus cyclophosphamide followed by paclitaxel or docetaxel Patients will also receive trastuzumab IV over 30-90 minutes for 52 weeks starting such that there is a minimum of 8 weeks of overlap with the standard of care chemotherapy. Trastuzumab may be given weekly, every 2 weeks, or every 3 weeks while overlapping with standard of care chemotherapy. Trastuzumab will be given every 3 weeks after all standard of care chemotherapy has concluded. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: Doxorubicin; Biological: Trastuzumab; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Epirubicin; Drug: Docetaxel; Drug: Carboplatin; Drug: Fluorouracil

Interventions

Doxorubicin DRUG

Also known as: Adriamycin®, Rubex®, Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin Hydrochloride

Arm I (definitive therapy); Arm II (definitive therapy, trastuzumab)

Trastuzumab BIOLOGICAL

Also known as: •Herceptin®

Arm II (definitive therapy, trastuzumab)

Cyclophosphamide DRUG

Also known as: Cytoxan®, CPM, CTX, CYT

Arm I (definitive therapy); Arm II (definitive therapy, trastuzumab)

Paclitaxel DRUG

Also known as: Abraxane®, Onxol®

Arm I (definitive therapy); Arm II (definitive therapy, trastuzumab)

Epirubicin DRUG

Also known as: Ellence, Pharmorubicin, Epirubicin ebewe

Arm I (definitive therapy); Arm II (definitive therapy, trastuzumab)

Docetaxel DRUG

Also known as: Taxotere, Docefrez

Arm I (definitive therapy); Arm II (definitive therapy, trastuzumab)

Carboplatin DRUG

Also known as: cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II), Paraplatin, Paraplatin-AQ

Arm II (definitive therapy, trastuzumab)

Fluorouracil DRUG

Also known as: 5-FU, Adrucil

Arm I (definitive therapy); Arm II (definitive therapy, trastuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed HER2-negative primary invasive ductal or invasive lobular breast carcinoma. For patients enrolling for neoadjuvant treatment, diagnosis must be clinical stage II or III; for patients enrolling for adjuvant treatment, diagnosis must be pathologic stage IIA to IIIC. Standard HER2 testing will be performed in the surgical specimen at Washington University according to the standard of care in the Department of Pathology. A HER2-negative primary breast cancer sample from a patient eligible for randomization should have a HER2 IHC score of 0 or 1+ Those patients with IHC score of 2+ should be HER2 FISH-negative in standard testing. Patient will have undergone staging studies including a CT of the chest/abdomen/pelvis and bone scan and/or PET scan either prior to the initiation of treatment or prior to entry into the trial. In addition, patients with non-metastatic, HER2-negative, recurrent tumors who need chemotherapy are eligible.
• Planning to receive best practice adjuvant or neoadjuvant chemotherapy according to institutional guidelines. Adjuvant tamoxifen or aromatase inhibitors treatment will be allowed for hormone receptor-positive patients. Patients who have failed neoadjuvant endocrine therapy will also be eligible.
• At least 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Patient (or legally authorized representative) must be able to understand and willing to sign a written informed consent document.

You may not qualify if:

• Prior chemotherapy for this cancer (excluding initiation of best practice chemotherapy to be given as standard of care as described in this protocol, which may be initiated after the pre-registration bone marrow collection but before final confirmation of eligibility and randomization).
• Previous treatment with trastuzumab or any other Her2 targeted therapy.
• Presence of an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Presence of bone marrow ERBB2 overexpressing DTCs at the time of diagnosis; bone marrow aspiration will be performed in consented patients to evaluate DTCs following pre-registration provided patients meet all eligibility criteria as described in this section.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Adequate cardiac function as demonstrated by LVEF of \>55% performed no more than 4 weeks prior to randomization.
• Normal organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• hemoglobin ≥ 10 g/dL
• total bilirubin within institutional upper limits of normal unless related to primary disease
• AST(SGOT)/ALT(SGPT) ≤2.0 X institutional upper limit of normal
• Creatinine ≤ 1.5 institutional upper limits of normal OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• If a woman of childbearing potential, patient must use two forms of effective contraception for a minimum of 6 months following trastuzumab. Effective methods of birth control include use of established oral, injected, or implanted hormonal methods of birth control, IUD, IUS, and condoms.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• Siddappa CM, Watson MA, Pillai SG, Trinkaus K, Fleming T, Aft R. Detection of disseminated tumor cells in the bone marrow of breast cancer patients using multiplex gene expression measurements identifies new therapeutic targets in patients at high risk for the development of metastatic disease. Breast Cancer Res Treat. 2013 Jan;137(1):45-56. doi: 10.1007/s10549-012-2279-y. Epub 2012 Nov 6.

  PMID: 23129172 BACKGROUND

• Rack B, Juckstock J, Gunthner-Biller M, Andergassen U, Neugebauer J, Hepp P, Schoberth A, Mayr D, Zwingers T, Schindlbeck C, Friese K, Janni W. Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients. Arch Gynecol Obstet. 2012 Feb;285(2):485-92. doi: 10.1007/s00404-011-1954-2. Epub 2011 Jun 30.

  PMID: 21717141 BACKGROUND

• Vincent-Salomon A, Pierga JY, Couturier J, d'Enghien CD, Nos C, Sigal-Zafrani B, Lae M, Freneaux P, Dieras V, Thiery JP, Sastre-Garau X. HER2 status of bone marrow micrometastasis and their corresponding primary tumours in a pilot study of 27 cases: a possible tool for anti-HER2 therapy management? Br J Cancer. 2007 Feb 26;96(4):654-9. doi: 10.1038/sj.bjc.6603584. Epub 2007 Jan 30.

  PMID: 17262082 BACKGROUND

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Trastuzumab; Cyclophosphamide; carboxypeptidase M; Paclitaxel; Albumin-Bound Paclitaxel; Epirubicin; Docetaxel; Carboplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Albumins; Coordination Complexes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Rebecca Aft, M.D., Ph.D.
• Organization: Washington University School of Medicine

aftr@wustl.edu

314-747-0063

Study Officials

• Rebecca Aft, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: January 29, 2013
• Study Start: December 19, 2013
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: November 1, 2022
• Results First Posted: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)