Clinical Trials /

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery

NCT01147016

Description:

RATIONALE: Neoadjuvant chemotherapy for women with stage II-III Her negative breast cancer followed by Her2Bi armed activated T cells (ATCs) may significantly improve the pathologic complete response (pCR) rate at the time of surgery. Arming ex vivo expanded T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Giving combination neoadjuvant chemotherapy followed by laboratory-treated T cells before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II clinical trial is studying how well giving laboratory-treated T cells after neoadjuvant chemotherapy works in treating women with stage II or stage III breast cancer undergoing surgery.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery
  • Official Title: A Phase II Study of Anti-CD3 x Anti-HER2/Neu (Her2Bi) Armed Activated T Cells (ATC) After Neoadjuvant Chemotherapy in Women With HER2/Neu (0-2+), Hormone Receptor (HR) Negative Stage II-III Breast Cancers

Clinical Trial IDs

  • ORG STUDY ID: CDR0000675211
  • SECONDARY ID: P30CA022453
  • SECONDARY ID: WSU-2010-056
  • NCT ID: NCT01147016
  • NCT ALIAS: NCT01658969

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
HER2Bi-armed activated T cellsHER2Bi-armed activated T cells + Neoadjuvant Chemotherapy
cyclophosphamideCytoxan®HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy
doxorubicin hydrochlorideAdriamycin®, Rubex®HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy
paclitaxelAbraxane®, Onxol®, TaxolHER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

Purpose

RATIONALE: Neoadjuvant chemotherapy for women with stage II-III Her negative breast cancer followed by Her2Bi armed activated T cells (ATCs) may significantly improve the pathologic complete response (pCR) rate at the time of surgery. Arming ex vivo expanded T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Giving combination neoadjuvant chemotherapy followed by laboratory-treated T cells before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II clinical trial is studying how well giving laboratory-treated T cells after neoadjuvant chemotherapy works in treating women with stage II or stage III breast cancer undergoing surgery.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate progression-free survival (PFS) in women with stage II-III triple-negative
      breast cancer without a complete pathologic response (cPR) who receive a regimen of
      neoadjuvant chemotherapy (chemoT), surgery, and/or irradiation followed by 8 infusions of
      ~10-15 x 10^9 Her2Bi-armed activated T cells (ATC) (aATC) given twice per week for 4 weeks in
      combination with IL-2 (aldesleukin) (300,000 IU/m^2/day) and GM-CSF (sargramostim) (250
      μg/m^2/twice per week) beginning 3 days before the 1st infusion and ending 1 week after the
      last infusion (defined as immunotherapy).

      II. To estimate the change from baseline (pre immunotherapy [IT]) to post-IT in specific
      cytotoxicity and interferon gamma (IFN-γ) enzyme-linked immunosorbent spots (Elispots) of
      lymphocytes in the blood directed at breast cancer cells.

      III. To investigate if pathologic response and the changes in numbers and proportion of
      infiltrating cells and cancer stem cells in the tumor at the time of surgery are associated
      with progressive disease.

      OUTLINE:

      NEOADJUVANT CHEMOTHERAPY: Patients receive dose-dense AC-T regimen comprising doxorubicin
      hydrochloride intravenously (IV) and cyclophosphamide IV once every 2 weeks for 4 courses
      followed by paclitaxel IV once every 2 weeks for 4 courses or paclitaxel IV once weekly for
      12 weeks. Or, patients receive TAC regimen comprising docetaxel IV, doxorubicin hydrochloride
      IV, and cyclophosphamide IV once every 3 weeks for 6 courses. Treatment continues in the
      absence of disease progression or unacceptable toxicity.

      IMMUNOTHERAPY: Beginning 3 weeks after the last dose of chemotherapy, patients receive
      Her2Bi-armed activated T cells IV over 5-30 minutes twice weekly for 4 weeks. Patients also
      receive aldesleukin subcutaneously (SC) daily beginning 3 days before the first T cell
      infusion and ending 1 week after the last infusion.

      SURGERY: Patients then undergo surgical resection of the breast 2 weeks later.

      After completion of study treatment, patients may be followed up at 1, 3, 6, and 12 months.
    

Trial Arms

NameTypeDescriptionInterventions
HER2Bi-armed activated T cells + Neoadjuvant ChemotherapyExperimentalHER2Bi-armed activated T cells - Total of 4 of the T cell infusions IV over a period of 1 month Cyclophosphamide, doxorubicin hydrochloride, paclitaxel -As prescribed by physician, standard of care.
  • cyclophosphamide
  • doxorubicin hydrochloride
  • paclitaxel

Eligibility Criteria

        Inclusion Criteria

          -  Signed and dated institutional review board (IRB)-approved consent form

          -  Women of reproductive potential must agree to use an effective nonhormonal method of
             contraception during therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and/or
             Karnofsky PS of >= 70%

          -  Diagnosis of invasive adenocarcinoma of the breast made by core needle biopsy

          -  Palpable primary breast tumor measuring >= 2.0 cm on physical exam or imaging prior to
             neoadjuvant chemotherapy

          -  Patients with stage II-IIIB breast cancer that is HER2-negative by
             immunohistochemistry (IHC) (0-2+) and fluorescence in situ hybridization (FISH)
             (HER2/chromosome enumeration probe [CEP]17 amplification ratio < 2.0) who have
             completed "third generation" neoadjuvant chemoT and planned local treatment (surgery
             and radiation if indicated); estrogen receptor (ER) or progesterone receptor (PR)
             status should be negative

          -  Patients may have lymph node positive or negative disease, as long as they have
             clinical/pathologic stage II or IIIB breast cancer; patients may have the lymph nodes
             assessed by any method deemed appropriate by the treating physicians, including
             pre-neoadjuvant therapy sentinel lymph node biopsy

          -  Presence of residual disease measuring at least 5mm (as single foci or in aggregate)
             on final pathology following surgery

          -  Patients must discontinue sex hormone therapy prior to registration, e.g. birth
             control pills, hormonal replacement therapy

          -  Absolute neutrophil count (ANC) must be >= 1000/mm^3

          -  Platelet count must be >= 100,000/mm^3

          -  Hemoglobin must be >= 9.0 mg/dL

          -  Total bilirubin must be =< the upper limit of normal (ULN) for the lab unless the
             patient has a grade 1 bilirubin elevation (> ULN to 1.5 x ULN) resulting from
             Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and

          -  Alkaline phosphatase must be =< 2.5 x ULN for the lab

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) must be =< 1.5 x ULN
             for the lab

          -  Alkaline phosphatase and AST/ALT may not both be > the ULN; for example, if the
             alkaline phosphatase is > the ULN but =< 2.5 x ULN, then the AST/ALT must be =< the
             ULN; if the AST/ALT is > the ULN but =< 1.5 x ULN, then the alkaline phosphatase must
             be =< ULN

          -  Patients with either skeletal pain or alkaline phosphatase that is > ULN must have a
             bone scan showing they do not have metastatic disease; suspicious findings on bone
             scan must be confirmed as benign by x-ray, magnetic resonance imaging (MRI), or biopsy

          -  Patients with AST/ALT or alkaline phosphatase > ULN must have liver imaging that does
             not demonstrate metastatic disease

          -  Patients with AST/ALT > ULN must have negative hepatitis studies

          -  Patients with stage II disease and clinical suspicion for metastatic disease based on
             reported symptoms, physical examination findings, or laboratory abnormalities must
             have staging studies demonstrating no evidence of metastatic disease (with exception
             of axillary lymph nodes or mammary nodes); patients with stage IIIA disease must have
             staging studies demonstrating no evidence of metastatic disease (with exception of
             axillary lymph nodes or mammary nodes), even if asymptomatic with normal physical
             examination and laboratory values; such staging studies must include: chest imaging
             (chest X-ray, computed tomography [CT], or MRI), abdominal/pelvis imaging (CT or MRI),
             and bone imaging (bone scan or positron emission tomography [PET]-scan); abnormalities
             that are indeterminate and too small to biopsy should be followed with further
             imaging, as appropriate, but do not exclude patients from the study; abnormalities
             that are suspicious and large enough to biopsy exclude patients from the study, unless
             a biopsy is performed and is negative for metastatic disease

          -  Serum creatinine =< 1.5 x ULN for the lab

          -  Pre-entry core biopsy with sufficient material for correlative studies

          -  Left Ventricular Ejection Fraction (LVEF) >= 45 % (by multigated acquisition scan
             [MUGA] or echocardiography)

        Exclusion Criteria

          -  Tumor determined to be HER2-positive by immunohistochemistry (3+) or by fluorescent in
             situ hybridization (HER2/CEP17 amplification ratio >= 2.0)

          -  Tumors clinically staged as anyT with N3 disease or unresectable disease

          -  Evidence of disease progression on neoadjuvant chemo T

          -  Definitive evidence of metastatic disease with exception of axillary lymph nodes or
             mammary nodes

          -  Synchronous bilateral breast cancer (invasive or ductal carcinoma in situ [DCIS])

          -  Treatment with biotherapy, and/or hormonal therapy for the currently diagnosed breast
             cancer prior to study entry

          -  Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement
             therapy, etc. within 2 weeks prior to the collection of cells

          -  Prior history of invasive breast cancer (patients with a history of DCIS or lobular
             carcinoma in situ [LCIS] are eligible)

          -  Other malignancies unless the patient is considered to be disease-free for 5 or more
             years prior to randomization and is deemed by the physician to be at low risk for
             recurrence; patients with the following cancers are eligible if diagnosed and treated
             within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the
             colon, melanoma in situ, and basal cell or squamous cell carcinoma of the skin

          -  Known cardiac disease which precludes their ability to receive planned treatments:

               -  Angina pectoris that requires the use of anti-anginal medication

               -  History of documented congestive heart failure

               -  Serious cardiac arrhythmia requiring medication

               -  Severe conduction abnormality

               -  Valvular disease with documented cardiac function compromise; and

               -  Uncontrolled hypertension defined as blood pressure (BP) that is consistently >
                  150/90 on antihypertensive therapy at the time of registration (Patients with
                  hypertension that is well controlled on medication are eligible)

          -  History of myocardial infarction (MI) documented by elevated cardiac enzymes with
             persistent regional wall motion abnormality on assessment of left ventricular (LV)
             function (patients with history of MI must have an echo instead of/in addition to a
             MUGA to evaluate LV wall motion)

          -  Symptomatic peripheral vascular disease

          -  Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would
             preclude treatment with any of the treatment regimens or would prevent required
             follow-up

          -  Chronic ongoing oral steroid use at the time of registration for any condition (such
             as asthma, rheumatoid arthritis, etc)

          -  Administration of any investigational agents within 30 days before study entry

          -  Pregnancy or lactation at the time of registration

          -  Psychiatric or addictive disorders or other conditions that in the opinion of the
             investigators would preclude the patient from complying with the study protocol
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response
Time Frame:Every 8 weeks or as indicated
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Every 3 months for the first year, and then every 6 months for one more year.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Barbara Ann Karmanos Cancer Institute

Trial Keywords

  • estrogen receptor-negative breast cancer
  • HER2-negative breast cancer
  • male breast cancer
  • progesterone receptor-negative breast cancer
  • recurrent breast cancer
  • stage IIA breast cancer
  • stage IIB breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • triple-negative breast cancer

Last Updated

December 5, 2016