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

NCT01147016 | Terminated Phase 2 Results DMC

• 3 other identifiers: 2010-056(b)P30CA022453WSU-2010-056
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Breast Cancer

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

Outcome Measures

Primary Outcomes (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

  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)

• Overall Deaths

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

Study Arms (1)

HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

EXPERIMENTAL

HER2Bi-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.

Biological: HER2Bi-armed activated T cells; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: paclitaxel; Other: laboratory biomarker analysis; Procedure: neoadjuvant therapy; Procedure: therapeutic conventional surgery

Interventions

HER2Bi-armed activated T cells BIOLOGICAL

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

HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

cyclophosphamide DRUG

As prescribed by physician, standard of care.

Also known as: Cytoxan®

HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

doxorubicin hydrochloride DRUG

As prescribed by physician, standard of care.

Also known as: Adriamycin®, Rubex®

HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

paclitaxel DRUG

As prescribed by physician, standard of care.

Also known as: Abraxane®, Onxol®, Taxol

HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

laboratory biomarker analysis OTHER

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.

HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

neoadjuvant therapy PROCEDURE

As prescribed by physician, standard of care.

HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

therapeutic conventional surgery PROCEDURE

As recommended by physician, post immunotherapy.

HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male; Triple Negative Breast Neoplasms

Interventions

Cyclophosphamide; Doxorubicin; Paclitaxel; Albumin-Bound Paclitaxel; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Combined Modality Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Amy Weise
• Organization: Barbara Ann Karmanos Cancer Institute

aweise3@hfhs.org

248-344-6688

Study Officials

• Amy Weise, M.D.

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: June 22, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2017
• Study Completion: July 26, 2017
• Last Updated: April 27, 2023
• Results First Posted: April 27, 2023

Record last verified: 2023-04

Locations

US (1)