Breast CancerPhase 2NCT01022138
Laboratory-Treated T Cells After Second-Line Chemotherapy in Treating Patients With HER2/Neu-Negative Metastatic Breast Cancer
A Phase 2 study testing HER2Bi-armed activated T cells, Cyclophosphamide and Laboratory biomarker analysis in people with Breast Cancer, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.
Trial 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. 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 Laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 2010to 19 Feb 2019
- 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
- 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.
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- 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.)
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201-1379
About this study
Official title: A Phase II Study of Anti-CD3 x Anti-HER2/Neu Armed Activated T Cells for Patients With HER2/Neu (0, 1+ or 2+) Metastatic Breast Cancers.
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.
Read the detailed description
OBJECTIVES:
- To determine in a phase II trial whether Her2Bi armed ATC infused after ChemoT for patients with HER2 0-2+ MBC or locally advanced, unresectable breast cancer would improve median PFS by 2 months beyond the median PFS of 2 months estimated from published trials in a one stage design.
- To determine the overall survival (OS) of patients with HER2 0-2+ MBC and locally advanced, unresectable breast cancer who receive aATC infusion after ChemoT.
- To confirm the toxicity profile for Her2Bi armed ATC given after ChemoT for patients with HER2 0-2+ MBC.
- To measure functional and phenotypic changes in immune cell populations (blood and tumor sites, if accessible) as a consequence of armed ATC (tumor biopsies done at KCI only). Cytokine responses, phenotypic markers of differentiation, and anti-tumor cytotoxicity will be examined.
- OUTLINE: Patients receive second-line chemotherapy for 4 courses or 4 months. Beginning as early as 1.5 weeks and as late as 4 weeks after chemotherapy, the patients will receive the first infusion of anti-CD3 x anti-HER2/neu bispecific antibody-armed activated T-cells (ATC) IV over 30-60 minutes once a week for 3 weeks. Low dose granulocyte-macrophage colony stimulating factor (250 µg/m2/twice per week) will start 3 days before the first aATC infusion and end with the last dose of aATC. Patients who are already on the protocol will be given a choice to add GM-CSF to their treatment regimen (after reconsenting) or continue to their treatment without GM-CSF. Patients then receive a boost of anti-CD3 x anti-HER2/neu bispecific antibody-armed ATC at 12 weeks after the 3rd ATC infusion.
Blood and tumor tissue samples may be collected periodically for biomarker and other analyses.
After completion of study therapy, patients are followed up periodically for ≥ 2 years.
- Conditions
- Breast Cancer
- Being tested
- HER2Bi-armed activated T cells, Cyclophosphamide, Laboratory biomarker analysis
- Keywords
- HER2-negative breast cancer, stage IV breast cancer, recurrent breast cancer
- Medical subject headings
- 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
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.
CyclophosphamideDrug
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 analysisOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: HER2Bi-armed activated T cells; Drug: Cyclophosphamide; Other: Laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At the 4-month follow-up
Secondary outcomes (2)
Overall Survival
Overall survival (OS) was defined as the time duration from the first infusion until death or last observation.
Measured: Followed until death or last observation (assessed up to 5 years), whichever occurs first
Overall Response Rate
Complete and partial responses; Responses will be evaluated using standard RECIST 1.1 criteria.
Measured: Following chemotherapy, up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2009 (estimated)
- Study start8 Mar 2010
- Primary completion6 Nov 2015
- Study completion19 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Ann Karmanos Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Abhinav Deol, Barbara Ann Karmanos Cancer Institute
- Investigators
- Abhinav Deol, M.D., Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01022138
- Sponsor's protocol ID
- 2009-085
- Other IDs
- P30CA022453, WSU-2009-085
- Status last verified
- Nov 2022
- First submitted
- 26 Nov 2009
- Last updated
- 23 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Anti-CD3 x Anti-HER2/Neu Armed Activated T Cells for Patients With HER2/Neu (0, 1+ or 2+) Metastatic Breast Cancers.
- ClinicalTrials.gov ID
- NCT01022138
- Acronym / sponsor ID
- 2009-085
- Conditions
- Breast Cancer
- Keywords
- HER2-negative breast cancer, stage IV breast cancer, recurrent breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 8 Mar 2010 (actual)
- Primary completion
- 6 Nov 2015 (actual)
- Study completion
- 19 Feb 2019 (actual)
- First posted
- 1 Dec 2009 (estimated)
- Results
- Posted 23 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
- To determine in a phase II trial whether Her2Bi armed ATC infused after ChemoT for patients with HER2 0-2+ MBC or locally advanced, unresectable breast cancer would improve median PFS by 2 months beyond the median PFS of 2 months estimated from published trials in a one stage design.
- To determine the overall survival (OS) of patients with HER2 0-2+ MBC and locally advanced, unresectable breast cancer who receive aATC infusion after ChemoT.
- To confirm the toxicity profile for Her2Bi armed ATC given after ChemoT for patients with HER2 0-2+ MBC.
- To measure functional and phenotypic changes in immune cell populations (blood and tumor sites, if accessible) as a consequence of armed ATC (tumor biopsies done at KCI only). Cytokine responses, phenotypic markers of differentiation, and anti-tumor cytotoxicity will be examined.
- OUTLINE: Patients receive second-line chemotherapy for 4 courses or 4 months. Beginning as early as 1.5 weeks and as late as 4 weeks after chemotherapy, the patients will receive the first infusion of anti-CD3 x anti-HER2/neu bispecific antibody-armed activated T-cells (ATC) IV over 30-60 minutes once a week for 3 weeks. Low dose granulocyte-macrophage colony stimulating factor (250 µg/m2/twice per week) will start 3 days before the first aATC infusion and end with the last dose of aATC. Patients who are already on the protocol will be given a choice to add GM-CSF to their treatment regimen (after reconsenting) or continue to their treatment without GM-CSF. Patients then receive a boost of anti-CD3 x anti-HER2/neu bispecific antibody-armed ATC at 12 weeks after the 3rd ATC infusion.
Blood and tumor tissue samples may be collected periodically for biomarker and other analyses.
After completion of study therapy, patients are followed up periodically for ≥ 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HER2Bi-armed activated T cells/Cyclophosphamide/biomarker | Experimental | Biological: HER2Bi-armed activated T cells, Drug: Cyclophosphamide, Other: Laboratory biomarker analysisHER2Bi-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. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (10 listed)
- 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):
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HER2Bi-armed activated T cellsImmediately after pheresis, the lymphocytes are activated with soluble monoclonal anti-CD3 antibody, which cross-links the CD3 receptors on T cells and activates them. | Biological | HER2Bi-armed activated T cells/Cyclophosphamide/biomarker |
| CyclophosphamideAfter 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 | Drug | HER2Bi-armed activated T cells/Cyclophosphamide/biomarker |
| Laboratory biomarker analysisThe 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. | Other | HER2Bi-armed activated T cells/Cyclophosphamide/biomarker |
Primary outcome
Number of Participant Who Were Alive Without Progression at 4 Months
Time frame: At the 4-month follow-up
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.
2 secondary outcomes
Overall Survival
Time frame: Followed until death or last observation (assessed up to 5 years), whichever occurs first
Overall Response Rate
Time frame: Following chemotherapy, up to 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abhinav Deol, M.D. principal investigator
Barbara Ann Karmanos Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HER2Bi-armed activated T cells, Cyclophosphamide and Laboratory biomarker analysis 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 13 inclusion and 10 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 23 Dec 2022. 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 23 Dec 2022). 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?
Number of Participant Who Were Alive Without Progression at 4 Months (time frame: At the 4-month follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Dec 2022.