Breast CancerPhase 2NCT00020722
Chemotherapy Followed by Peripheral Stem Cell Transplantation Plus Biological Therapy in Treating Women With Stage IV Breast Cancer
A Phase 2 study testing therapeutic autologous lymphocytes, Ifosfamide, carboplatin, and etoposide (ICE) regimen and Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC) 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 use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation plus biological therapy may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- therapeutic autologous lymphocytes, Ifosfamide, carboplatin, and etoposide (ICE) regimen and Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Mar 2013
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Women with histologically documented metastatic carcinoma of the breast
- Bilateral disease allowed
- Concurrent intraductal or lobular carcinoma in situ allowed
- Measurable or evaluable recurrent metastatic disease (stage IV) documented by radiograph, CT scan, nuclear medicine scan, or physical exam
- Biopsy of recurrent site(s) recommended but not required
- Nonmeasurable disease allowed if tumor or metastatic disease has been previously removed or successfully treated
- 0 to 3+ HER2 amplification, as determined by FISH
- No clinical evidence of active brain metastases
- Patients with treated brain metastases (i.e., those who have received definitive radiation, chemotherapy, and/or underwent surgery) and are stable are eligible
- Hormone receptor status:
- Estrogen or progesterone receptor positive or negative
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- Karnofsky performance status 70-100% OR ECOG performance status 0-2
- Life expectancy at least 3 months
- Granulocyte count at least 1,500/mm^3
- Platelet count at least 50,000/mm^3
- Hemoglobin greater than 8 g/dL
- Bilirubin less than 1.5 times normal
- AST, ALT, and alkaline phosphatase < 5 times upper normal
- Creatinine less than 1.8 mg/dL
- Creatinine clearance at least 60 mL/min
- BUN less than 1.5 times normal
- No myocardial infarction (MI) within the past year
- No history of MI (> 1 year ago) with current coronary symptoms requiring medication
- No current history of angina/coronary symptoms requiring medication
- No clinical evidence of congestive heart failure requiring medical management
- No significant congestive heart failure
- No other uncontrolled or significant cardiovascular disease
- Ejection fraction at least 45% at rest by MUGA
- Systolic BP < 130 mm Hg and diastolic BP < 80 mm Hg
- BP must be controlled to meet the standard by anti-hypertensive medications for at least 7 days prior to the first infusion
- PFT-FEV_1 at least 50% predicted
- DLCO2 at least 50% predicted
- FVC at least 50% predicted
- No other malignancy within the past 3 years
- No other serious medical or psychiatric illness that would preclude study participation
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior chemotherapy regimens allowed, including prior treatment on protocol WSU-2006-130
- Prior vaccine therapy on protocol WSU-2006-130 allowed
- More than 4 weeks to leukapheresis since prior hormonal therapy
- No radiation to the axial skeleton within 4 weeks of leukapheresis
- No concurrent hormonal therapy for breast cancer
- Hormones administered for non-disease-related condition (e.g. insulin for diabetes) allowed
- Concurrent steroids for adrenal failure, septic shock, or pulmonary toxicity allowed
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: Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation plus biological therapy may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: This phase II trial is studying how well chemotherapy followed by peripheral stem cell transplantation plus biological therapy works in treating women with stage IV breast cancer.
Read the detailed description
OBJECTIVES:
- Determine whether the use of autologous peripheral blood stem cell transplantation followed by immunotherapy with activated T cells in women with stage IV breast cancer improves progression-free survival (PFS) compared to a reported mean PFS in patients treated with second-line chemotherapy with matching inclusion criteria by published trials.
- Determine if this regimen improves clinical response and overall survival.
- Perform sequential immune monitoring studies, including phenotyping, cytotoxic assays, EliSpots for IFNγ, selected T-cell repertoire (Vβ analysis), HER2/new tetramer analysis, and serum tumor markers.
- Test correlations between immune function tests and clinical endpoints.
OUTLINE: Patients are stratified according to tumor classification (chemosensitive vs chemoresistant).
Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days followed by peripheral blood mononuclear cell (PBMC) collection for PBSCT and generation of activated T cells (ATC). The PBMC are treated ex vivo with monoclonal antibody OKT3 to form ATC. The ATC are expanded for 12-14 days in interleukin-2 (IL-2).
Patients then receive high-dose chemotherapy. Patients with chemosensitive disease receive cyclophosphamide IV over 1 hour, thiotepa IV over 1 hour, and carboplatin IV over 1 hour on days -4, -3, and -2. Patients with chemoresistant disease receive ifosfamide IV over 1 hour, etoposide IV twice daily, and carboplatin IV over 1 hour on days -8 to -3. Patients undergo autologous PBSC transplantation on day 0 or on both day 0 and day 1.
Patients then receive ATC IV over 15-20 minutes three times per week starting approximately on day +1 for three weeks and then once weekly for at least 6 doses.
After completion of study therapy, patients are followed periodically for up to 2 years after PBSC.
- Conditions
- Breast Cancer
- Being tested
- therapeutic autologous lymphocytes, Ifosfamide, carboplatin, and etoposide (ICE) regimen, Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC), Leukapheresis, peripheral blood stem cell transplantation (PBSCT)
- Keywords
- 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.
therapeutic autologous lymphocytesBiological
Immediately after pheresis, the lymphocytes will be activated with soluble monoclonal anti-CD3 antibody (OKT3) which cross-links the CD3 receptors on T cells and activates T cells.
The time for ATC infusions will vary from patient to patient, but the infusion rate will be based on the rate calculated from the endotoxin level in the cell product. All patients will be observed for at least 1 hr after an infusion.
Ifosfamide, carboplatin, and etoposide (ICE) regimenDrug
Also called Ifex®, Paraplatin ®, Toposar®, VePesid®
Ifosfamide 2,500 mg/m2 given IV daily on day -8, -7, -6, -5, -4, and -3 prior to PBSCT. Ifosfamide 2,500 mg/m2 infused IV over 1 hour (hour 0-1) on days -8 to -3 for a total dose of 15,000 mg/m2.
Mesna will be administered per BMT Standard of Care Guideline at a dose of 25% of the total Ifosfamide dose 30 minutes prior to and then 3, 6, and 9 hours after ifosfamide daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 2500 mg/m2.
Carboplatin at a dose of 250 mg/m2 will be given daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 1500 mg/m2.
VP-16 (etoposide) at a dose of 200 mg/m2 will be given IV on days -8, -7, -6, -5, -4 and -3. The total dose of VP-16 given prior to PBSCT will be 2,400 mg/m2. VP-16 will be given 200 mg/m2
Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC)Drug
Also called Cytoxan®, Neosar®, Paraplatin ®
Cyclophosphamide will be given at a dose of 2000 mg/m2 in NS IV over one hour daily on days -4, -3, and -2 (total = 6000 mg/m2).
Thiotepa will be given at a dose of 167 mg/m2 in NS IV over one hour daily on days -4, -3, -2 (total = 500 mg/m2) as the preparative regimen followed by PBSCT on day 0.
Carboplatin will be given at a dose of 267 mg/m2 in D5W IV over one hour daily on days -4, -3, and -2.
Mesna will be administered per BMT Standard of Care Guidelines at a dose of 25% of the total cyclophosphamide dose 30 minutes prior to and then 3, 6, and 9 hours after cyclophosphamide daily on days -4, -3, and -2 prior to PBSCT for a total of 2000mg/m2.
LeukapheresisProcedure or surgery
Peripheral blood mononuclear cells (PBMC) will be collected by leukapheresis (for generation of ATC) prior to or post G-CSF (16 ug/kg/day) priming for collecting stem cells.
peripheral blood stem cell transplantation (PBSCT)Procedure or surgery
Will be collected either before or after peripheral blood stem cell collection for stem cell transplant.
| Study group | Role | What they receive |
|---|---|---|
| therapeutic autologous lymphocytes | Experimental | Not described Receives: Biological: therapeutic autologous lymphocytes; Drug: Ifosfamide, carboplatin, and etoposide (ICE) regimen; Drug: Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC); Procedure: Leukapheresis; Procedure: peripheral blood stem cell transplantation (PBSCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free Survival
Measured: Length of time from day of transplant until recurrence or relapse.
Secondary outcomes (1)
Overall Survival
Measured: Length of time from day of transplant until death.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startAug 2007
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: Lack of funding to continue study.
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
- 7 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, Lawrence Lum, Barbara Ann Karmanos Cancer Institute
- Investigators
- Lawrence G. Lum, MD, DSc, Study chair, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00020722
- Sponsor's protocol ID
- CDR0000068707
- Other IDs
- P30CA022453, WSU-2007-033, RWMC-0634246
- Status last verified
- Feb 2016
- First submitted
- 11 Jul 2001
- Last updated
- 17 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II)
- ClinicalTrials.gov ID
- NCT00020722
- Acronym / sponsor ID
- CDR0000068707
- Conditions
- Breast Cancer
- Keywords
- stage IV breast cancer, recurrent breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding to continue study.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2007
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 30 Mar 2015
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 use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation plus biological therapy may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: This phase II trial is studying how well chemotherapy followed by peripheral stem cell transplantation plus biological therapy works in treating women with stage IV breast cancer.
Detailed description
OBJECTIVES:
- Determine whether the use of autologous peripheral blood stem cell transplantation followed by immunotherapy with activated T cells in women with stage IV breast cancer improves progression-free survival (PFS) compared to a reported mean PFS in patients treated with second-line chemotherapy with matching inclusion criteria by published trials.
- Determine if this regimen improves clinical response and overall survival.
- Perform sequential immune monitoring studies, including phenotyping, cytotoxic assays, EliSpots for IFNγ, selected T-cell repertoire (Vβ analysis), HER2/new tetramer analysis, and serum tumor markers.
- Test correlations between immune function tests and clinical endpoints.
OUTLINE: Patients are stratified according to tumor classification (chemosensitive vs chemoresistant).
Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days followed by peripheral blood mononuclear cell (PBMC) collection for PBSCT and generation of activated T cells (ATC). The PBMC are treated ex vivo with monoclonal antibody OKT3 to form ATC. The ATC are expanded for 12-14 days in interleukin-2 (IL-2).
Patients then receive high-dose chemotherapy. Patients with chemosensitive disease receive cyclophosphamide IV over 1 hour, thiotepa IV over 1 hour, and carboplatin IV over 1 hour on days -4, -3, and -2. Patients with chemoresistant disease receive ifosfamide IV over 1 hour, etoposide IV twice daily, and carboplatin IV over 1 hour on days -8 to -3. Patients undergo autologous PBSC transplantation on day 0 or on both day 0 and day 1.
Patients then receive ATC IV over 15-20 minutes three times per week starting approximately on day +1 for three weeks and then once weekly for at least 6 doses.
After completion of study therapy, patients are followed periodically for up to 2 years after PBSC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| therapeutic autologous lymphocytes | Experimental | Biological: therapeutic autologous lymphocytes, Drug: Ifosfamide, carboplatin, and etoposide (ICE) regimen, Drug: Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC), Procedure: Leukapheresis, Procedure: peripheral blood stem cell transplantation (PBSCT) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| therapeutic autologous lymphocytesImmediately after pheresis, the lymphocytes will be activated with soluble monoclonal anti-CD3 antibody (OKT3) which cross-links the CD3 receptors on T cells and activates T cells. The time for ATC infusions will vary from patient to patient, but the infusion rate will be based on the rate calculated from the endotoxin level in the cell product. All patients will be observed for at least 1 hr after an infusion. | Biological | therapeutic autologous lymphocytes |
| Ifosfamide, carboplatin, and etoposide (ICE) regimenAlso: Ifex®, Paraplatin ®, Toposar®, VePesid®Ifosfamide 2,500 mg/m2 given IV daily on day -8, -7, -6, -5, -4, and -3 prior to PBSCT. Ifosfamide 2,500 mg/m2 infused IV over 1 hour (hour 0-1) on days -8 to -3 for a total dose of 15,000 mg/m2. Mesna will be administered per BMT Standard of Care Guideline at a dose of 25% of the total Ifosfamide dose 30 minutes prior to and then 3, 6, and 9 hours after ifosfamide daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 2500 mg/m2. Carboplatin at a dose of 250 mg/m2 will be given daily on days -8, -7, -6, -5, -4, and -3 prior to PBSCT for a total dose of 1500 mg/m2. VP-16 (etoposide) at a dose of 200 mg/m2 will be given IV on days -8, -7, -6, -5, -4 and -3. The total dose of VP-16 given prior to PBSCT will be 2,400 mg/m2. VP-16 will be given 200 mg/m2 | Drug | therapeutic autologous lymphocytes |
| Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC)Also: Cytoxan®, Neosar®, Paraplatin ®Cyclophosphamide will be given at a dose of 2000 mg/m2 in NS IV over one hour daily on days -4, -3, and -2 (total = 6000 mg/m2). Thiotepa will be given at a dose of 167 mg/m2 in NS IV over one hour daily on days -4, -3, -2 (total = 500 mg/m2) as the preparative regimen followed by PBSCT on day 0. Carboplatin will be given at a dose of 267 mg/m2 in D5W IV over one hour daily on days -4, -3, and -2. Mesna will be administered per BMT Standard of Care Guidelines at a dose of 25% of the total cyclophosphamide dose 30 minutes prior to and then 3, 6, and 9 hours after cyclophosphamide daily on days -4, -3, and -2 prior to PBSCT for a total of 2000mg/m2. | Drug | therapeutic autologous lymphocytes |
| LeukapheresisPeripheral blood mononuclear cells (PBMC) will be collected by leukapheresis (for generation of ATC) prior to or post G-CSF (16 ug/kg/day) priming for collecting stem cells. | Procedure or surgery | therapeutic autologous lymphocytes |
| peripheral blood stem cell transplantation (PBSCT)Will be collected either before or after peripheral blood stem cell collection for stem cell transplant. | Procedure or surgery | therapeutic autologous lymphocytes |
Primary outcome
Disease-free Survival
Time frame: Length of time from day of transplant until recurrence or relapse.
1 secondary outcome
Overall Survival
Time frame: Length of time from day of transplant until death.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
- 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.
Lawrence G. Lum, MD, DSc study chair
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 therapeutic autologous lymphocytes, Ifosfamide, carboplatin, and etoposide (ICE) regimen and Cyclophosphamide, Thiotepa, Carboplatin (CTC) or STAMP V (CTC) 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?
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 17 Feb 2016. 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 30 Mar 2015). 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?
Disease-free Survival (time frame: Length of time from day of transplant until recurrence or relapse.). 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 17 Feb 2016.