Clinical Trials /

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

NCT01779050

Description:

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. Administering targeted trastuzumab therapy to these patients may result in the elimination of HER2 expressing disseminated tumor cells and improved disease free survival.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Disseminated Tumor Cells
  • Official Title: A Phase II Randomized Trial Evaluating the Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Bone Marrow Disseminated Tumor Cells

Clinical Trial IDs

  • ORG STUDY ID: 201309084
  • NCT ID: NCT01779050

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
DoxorubicinAdriamycin®, Rubex®, Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin HydrochlorideArm I (definitive therapy)
TrastuzumabHerceptin®Arm II (definitive therapy, trastuzumab)
CyclophosphamideCytoxan®, CPM, CTX, CYTArm I (definitive therapy)
PaclitaxelAbraxane®, Onxol®Arm I (definitive therapy)
EpirubicinEllence, Pharmorubicin, Epirubicin ebeweArm I (definitive therapy)
DocetaxelTaxotere, DocefrezArm I (definitive therapy)
Carboplatincis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II), Paraplatin, Paraplatin-AQArm II (definitive therapy, trastuzumab)
Fluorouracil5-FU, AdrucilArm I (definitive therapy)

Purpose

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. Administering targeted trastuzumab therapy to these patients may result in the elimination of HER2 expressing disseminated tumor cells and improved disease free survival.

Trial Arms

NameTypeDescriptionInterventions
Arm I (definitive therapy)Active ComparatorPatients 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
  • Doxorubicin
  • Cyclophosphamide
  • Paclitaxel
  • Epirubicin
  • Docetaxel
  • Fluorouracil
Arm II (definitive therapy, trastuzumab)ExperimentalPatients 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.
  • Doxorubicin
  • Cyclophosphamide
  • Paclitaxel
  • Epirubicin
  • Docetaxel
  • Carboplatin
  • Fluorouracil

Eligibility Criteria

        Pre-Registration Inclusion Criteria:

          -  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.

        Pre-Registration Exclusion Criteria:

          -  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.

        Registration Inclusion Criteria

          -  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.

        Registration Exclusion Criteria

          -  Evidence of distant metastasis present by CT scan, bone scan, or physical exam.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to trastuzumab.

          -  Prior chemotherapy for this cancer (excluding initiation of best practice chemotherapy
             to be given as standard of care described in this protocol, which may be initiated
             after the pre-registration bone marrow collection but before final confirmation of
             eligibility and randomization).

          -  History of other malignancy ≤ 5 years previous with the exception of basal cell or
             squamous cell carcinoma of the skin which were treated with local resection only or
             carcinoma in situ of the cervix.

          -  Pregnant or breastfeeding. Patient must have a negative serum pregnancy test ≤ 7 days
             from date of registration (if a woman of childbearing potential).

          -  Clinically important history of active liver disease, including viral or other
             hepatitis or cirrhosis.

          -  Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as
             less than the lower limit of normal for the institution despite adequate electrolyte
             supplementation.

          -  Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
             resulting in dyspnea at rest.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recurrence Rate at 3 years
Time Frame:3 years after completion of standard chemotherapy and surgery
Safety Issue:
Description:Rate for patients receiving trastuzumab in addition to standard chemotherapy and for patients receiving standard chemotherapy alone; calculated using Cox proportional hazards models

Secondary Outcome Measures

Measure:Elimination of ERBB2 overexpressing bone marrow DTCs
Time Frame:6-18 months
Safety Issue:
Description:Bone marrow samples collected at baseline and 6-18 months later; Fisher's exact test will be used to compare the proportion of patients who eliminate ERBB2-positive DTCs from BM in the two study arms.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

January 31, 2018