Laboratory-Treated T Cells After Second-Line Chemotherapy in Treating Patients With HER2/Neu-Negative Metastatic Breast Cancer

NCT01022138 | Terminated Phase 2 Results DMC

• 3 other identifiers: 2009-085P30CA022453WSU-2009-085
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Treating a patient's T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Giving laboratory-treated T cells after chemotherapy may be an effective treatment for breast cancer. PURPOSE: This phase II trial is studying how well giving laboratory-treated T cells after second-line chemotherapy works in treating patients with HER2/neu-negative metastatic breast cancer.

Conditions

Breast Cancer

Keywords

HER2-negative breast cancer; stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participant Who Were Alive Without Progression at 4 Months

  26 evaluable patients will be accrued in this study. A single-arm, single-stage phase II design will be used. If ≥9 out of 26 patients have not progressed by the 4-month follow-up, we will declare that the treatment is effective on TTP.

  At the 4-month follow-up

Secondary Outcomes (2)

• Overall Survival

  Followed until death or last observation (assessed up to 5 years), whichever occurs first

• Overall Response Rate

  Following chemotherapy, up to 4 months

Study Arms (1)

HER2Bi-armed activated T cells/Cyclophosphamide/biomarker

EXPERIMENTAL

HER2Bi-armed activated T cells Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them. Cyclophosphamide After recovering from the last cycle of chemotherapy (approx. two-four weeks) patients will be re-staged. If there are no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide Laboratory biomarker analysis The association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.

Biological: HER2Bi-armed activated T cells; Drug: Cyclophosphamide; Other: Laboratory biomarker analysis

Interventions

HER2Bi-armed activated T cells BIOLOGICAL

Immediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them.

HER2Bi-armed activated T cells/Cyclophosphamide/biomarker

Cyclophosphamide DRUG

After recovering from the last cycle of chemotherapy (approx. two-four weeks) patients will be re-staged. If there are no residual chemotherapy related toxicities, they will be given lymphodepleting chemotherapy consisting of one dose of Cyclophosphamide 1.0 gm/m2 on day -7. Appropriate anti-emetics will be given as pre-medications before the dose of Cyclophosphamide

HER2Bi-armed activated T cells/Cyclophosphamide/biomarker

Laboratory biomarker analysis OTHER

The association between the \[18F\]-FDG PET/CT assessments (percent changes from baseline in SUVpeak) and immunologic biomarker changes as well as tumor response will be explored.

HER2Bi-armed activated T cells/Cyclophosphamide/biomarker

Eligibility Criteria

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

You may qualify if:

• Metastatic Breast Cancer. Histologically confirmed breast cancer with evidence of metastatic disease (need not be biopsy proven) or locally, advanced unresectable disease.
• Patients with 0-2+ HER2 expression as determined by immunohistochemistry staining and/or FISH ratio \<2.0, with the above pathologic criteria will be eligible.
• Hormone Therapy. Patients on prior hormonal therapy are eligible. Hormonal therapy will be stopped 2 weeks prior to leukopheresis. Hormone therapy may be restarted after leukopheresis
• Patients may have received any number of prior lines of chemotherapy providing Leukopheresis is done when the lymphocyte count has recovered to ≥500 cells/mm3 and there are no residual chemotoxicities that would prevent leukopheresis.
• Patients who have received Radiotherapy are eligible providing Leukopheresis is done at least 4 weeks after radiation to the axial skeleton.
• Patients who have received prior biological agents are eligible.
• Patients with measurable and non-measurable disease are eligible.
• Age \> or = to 18 years
• ECOG 0-1 or Karnofsky \> or = to 70%
• Life expectancy \> or = to 3 months
• Patients with treated brain metastases are eligible
• Required Laboratory Data Granulocytes \> 1,200/mm3 Platelet count \> 50,000/μl Hemoglobin ≥ 8 gm/dl BUN \< 1.5 times normal Serum creatinine \< 1.8 mg/dl Creatinine Cl ≥50 ml/mm (can be calculated utilizing the Cockcroft \& Gault equation: Creatinine Clearance (mL/min) = {(140 - Age)} x Wt \[kg\] (x 0.85 if Female}/ {72 x SCr \[mg/dL\]} Bilirubin \< 1.5 times normal ALT, AST and alkaline phosphatase \< 5 times upper normal Negative HIV Negaitve Hepatitis B surface antigen Negative Hepatitis C serology LVEF ≥ 45% at rest (MUGA or ECHO) PFT-FEV1, DLCO, and FVC ≥ 50% of predicted
• Negative serum test for pregnancy, unless male, prior hysterectomy, tubal ligation, or postmenopausal. (Note: postmenopausal is defined as age\>55 with amenorrhea for \>1 year or age \<55 years with amenorrhea for 2 years and FSH level within postmenopausal range of institutional parameters; patients requiring FSH level to determine menopausal status need not have this performed and may choose to proceed with serum pregnancy testing.)

You may not qualify if:

• Patients with HER2 overexpression by immunohistochemistry (IHC) or overamplification by FISH are not eligible and are defined as follows: IHC staining of 3+ (uniform, intense membrane staining of \> 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.0.
• Patients with a history of another malignancy within 5 years of study entry are not eligible (except basal cell skin carcinoma and carcinoma-in-situ of the cervix).
• No serious medical or psychiatric illness which prevents informed consent or intensive treatment is allowed.
• Patients will be ineligible for treatment on this protocol if (prior to protocol entry):
• There is a history of a recent myocardial infarction (within one year)
• There is a history of a past myocardial infarction (more than one year ago) along with current coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF \< 45% by MUGA or ECHO)
• There is a current history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF \< 45% by MUGA or ECHO)
• There is clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA or ECHO results)
• Patients will be ineligible if there is recurrent pleural effusion or ascites requiring drainage (through thoracentesis, paracentesis, or indwelling device) more often than once every 4 weeks.
• Patients with clinical evidence of active CNS metastases are ineligible for therapy on this protocol.

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

Interventions

Cyclophosphamide

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

Results Point of Contact

• Title: Dr. Abhinav Deol
• Organization: Karmanos Cancer Institute

deola@karmanos.org

313-576-8093

Study Officials

• Abhinav Deol, 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: November 26, 2009
• First Posted: December 1, 2009
• Study Start: March 8, 2010
• Primary Completion: November 6, 2015
• Study Completion: February 19, 2019
• Last Updated: December 23, 2022
• Results First Posted: December 23, 2022

Record last verified: 2022-11

Locations

US (1)