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Breast CancerPhase 2NCT01147016

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

A Phase 2 study testing HER2Bi-armed activated T cells, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Breast Cancer
What is being tested?
HER2Bi-armed activated T cells, cyclophosphamide and doxorubicin hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
Jul 2010to 26 Jul 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

Conditions
Breast Cancer
Being tested
HER2Bi-armed activated T cells, cyclophosphamide, doxorubicin hydrochloride, paclitaxel, laboratory biomarker analysis
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
Medical subject headings
Breast Neoplasms, Breast Neoplasms, Male, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HER2Bi-armed activated T cellsBiological

    Total of 4 of the T cell infusions intravenously over a period of 1 month.

  • cyclophosphamideDrug

    Also called Cytoxan®

    As prescribed by physician, standard of care.

  • doxorubicin hydrochlorideDrug

    Also called Adriamycin®, Rubex®

    As prescribed by physician, standard of care.

  • paclitaxelDrug

    Also called Abraxane®, Onxol®, Taxol

    As prescribed by physician, standard of care.

  • laboratory biomarker analysisOther

    Immune studies will be done pre-immunotherapy, prior to the third infusion of activated T-cells, at the time of surgery, and 1 month after immunotherapy. If there are positive findings, additional optional studies will be done at 3, 6, and 12 months, if the immune studies show changes worthy of follow-up studies.

  • neoadjuvant therapyProcedure or surgery

    As prescribed by physician, standard of care.

  • therapeutic conventional surgeryProcedure or surgery

    As recommended by physician, post immunotherapy.

Study groups in NCT01147016
Study groupRoleWhat they receive
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.
Receives: Biological: HER2Bi-armed activated T cells; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Other: laboratory biomarker analysis; Procedure: neoadjuvant therapy; Procedure: therapeutic conventional surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 years..

Secondary outcomes (1)

  1. Overall Deaths

    Total number of deaths

    Measured: From date of randomization until date of death from any cause or end of study, whichever came first, assessed up to 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2010 (estimated)
  2. Study startJul 2010
  3. Primary completion1 Jul 2017
  4. Study completion26 Jul 2017

Why it stopped: Primary co-investigator leaving the institution \& funding transfer.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01147016
Sponsor's protocol ID
2010-056(b)
Other IDs
P30CA022453, WSU-2010-056
Status last verified
Apr 2023
First submitted
17 Jun 2010
Last updated
27 Apr 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HER2Bi-armed activated T cells, cyclophosphamide and doxorubicin hydrochloride in people with Breast Cancer, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 years..). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01147016.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2023.

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