Male Breast CancerPhase 1/2NCT00425672
ONTAK® in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment
A Phase 1/2 study testing ONTAK, flow cytometry and immunohistochemistry staining method in people with Male Breast Cancer and Recurrent Breast Cancer, run by University of Washington at 1 site in United States.
Trial summary
RATIONALE: ONTAK may be able to help reduce the type of cells that prevent other types of immune cells from attacking the breast cancer cells. PURPOSE: This phase I/II trial is studying the safety of ONTAK and its possible side effects to see how well it works in treating patients with advanced breast cancer that did… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Male Breast Cancer, Recurrent Breast Cancer, Stage IIIA Breast Cancer
- What is being tested?
- ONTAK, flow cytometry and immunohistochemistry staining method
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Apr 2010
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with advanced stage refractory breast cancer
- Progressive or relapsed disease following standard therapy
- Patients must have measurable disease that can include, but is not limited to bone; specifically, patients must have measurable extraskeletal disease that can be accurately measured in at least one dimension as >= 20 mm with conventional CT techniques or >= 10 mm with spiral CT scan; measurable (bi-dimensional) chest wall disease will also be allowed
- Patients must be at least 14 days out from last cytotoxic chemotherapy; patients on bisphosphonates are eligible
- White blood cell count (WBC) > 3.0 THOU/ul
- ANC > 1.0 THOU/ul
Show all 14Show fewer
- Platelets >= 100 THOU/ul
- Serum creatinine =< 2.0 mg/dL or creatinine clearance (calculated) >= 60 ml/min
- ALT/AST =< 2.0 x upper limit of normal
- Total bilirubin =< 1.5 x upper limit of normal
- Albumin >= 3.0 g/dL
- Subjects must have a Performance Status Score (ECOG Scale) =< 2
- Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment
- Men and women of reproductive ability must agree to contraceptive use during the study and for 1month after ONTAK treatment is discontinued
Who cannot join
- Prior treatment with ONTAK (DAB389 IL-2) or DAB486 IL-2
- Known history of hypersensitivity to diphtheria toxin or IL-2
- Active autoimmune disease
- Known history of pulmonary disease except controlled asthma
- History of or pre-existing, cardiovascular disease as defined by New York Heart Association (NYHA) Class III-IV categorization
- Pregnant or breast-feeding women
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Phase I-II Study of Denileukin Diftitox (ONTAK®) in Patients With Advanced Refractory Breast Cancer
RATIONALE: ONTAK may be able to help reduce the type of cells that prevent other types of immune cells from attacking the breast cancer cells.
PURPOSE: This phase I/II trial is studying the safety of ONTAK and its possible side effects to see how well it works in treating patients with advanced breast cancer that did not respond to previous treatment.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety of ONTAK infusion in patients with advanced refractory breast cancer.
II. To evaluate the effect of ONTAK administration on peripheral blood T-regulatory cells.
SECONDARY OBJECTIVES:
- To evaluate the incidence of IL-2R expression in tumor samples and investigate the correlation of tumor IL-2R expression and tumor response to ONTAK therapy.
II. To evaluate levels of circulating sIL-2R before and after ONTAK therapy. III. To evaluate the effect of ONTAK on endogenous tumor specific immunity. IV. To evaluate the potential anti-tumor effects of ONTAK in patients with advanced refractory breast cancer.
OUTLINE:
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
- Conditions
- Male Breast Cancer, Recurrent Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer
- Being tested
- ONTAK, flow cytometry, immunohistochemistry staining method, enzyme-linked immunosorbent assay, laboratory biomarker analysis
- Medical subject headings
- Breast Neoplasms, Male, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONTAKBiological
Also called DAB389 interleukin-2, DAB389 interleukin-2 immunotoxin, DAB389-IL2, DAB389IL-2
Given IV
flow cytometryOther
Correlative studies
immunohistochemistry staining methodOther
Also called immunohistochemistry
Correlative studies
enzyme-linked immunosorbent assayOther
Also called ELISA
Correlative studies
laboratory biomarker analysisOther
Correlative studies
protein expression analysisGenetic
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: ONTAK; Other: flow cytometry; Other: immunohistochemistry staining method; Other: enzyme-linked immunosorbent assay; Other: laboratory biomarker analysis; Genetic: protein expression analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0
Subjects are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, serum albumin, complete blood counts, symptom assessment, and physical exams performed at every cycle until 3 weeks after the final dose of ONTAK. All adverse events for all systems are graded on a scale of 1-5 using CTCAE v3.0.
Measured: 7 Days after last dose of ONTAK
Efficacy of ONTAK in Depleting T-regulatory Cells as a Decrease in Peripheral Blood Tregs Using Flow Cytometry
The efficacy of ONTAK in depleting Tregs will be defined as a decrease in peripheral blood Tregs by 25% of each individual subject's baseline. All subjects will undergo blood draws at baseline and post ONTAK infusions at designated time points. Tregs from the peripheral blood will be quantitated using flow cytometry.
Measured: 21 days after cycle 6
Secondary outcomes (4)
Incidence of Interleukin-2 (IL-2) and IL-2 Receptor (IL-2R) Expression in Tumor Samples by Immunohistochemical (IHC) Analysis
The incidence of IL-2 expression and its receptor complex, IL-2R in tumor samples will be evaluated by IHC analysis. Tumor sections will be interpreted as either positive or negative.
Measured: 21 days after cycle 6
Presence of Circulating sIL-2R in the Peripheral Blood
Evaluate levels of circulating sIL-2R (pg/ml) in the peripheral blood assessed before and after ONTAK therapy. Changes from baseline will be tabulated.
Measured: 21 days after cycle 6
Presence of Endogenous Tumor-specific Immunity
Evaluate the effect of ONTAK on endogenous tumor specific immunity
Measured: 21 days after cycle 6
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
Anti-tumor effects of ONTAK will be determined by evaluating tumor response and progression per RECIST. An objective response to ONTAK will be defined as achieving a CR or PR. Analysis of the data will include determination of complete (CR) and partial response (PR) rates, as well as stable (SD) and progressive disease (PD).
Measured: 21 days after cycle 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2007 (estimated)
- Study startSep 2005
- Primary completionApr 2010
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 Male Breast CancerStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Mary (Nora) Disis, University of Washington
- Investigators
- Lupe Salazar, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00425672
- Sponsor's protocol ID
- 6308 (FH/UWCC ID)
- Other IDs
- NCI-2010-00800, 127
- Status last verified
- Nov 2018
- First submitted
- 19 Jan 2007
- Last updated
- 5 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Study of Denileukin Diftitox (ONTAK®) in Patients With Advanced Refractory Breast Cancer
- ClinicalTrials.gov ID
- NCT00425672
- Acronym / sponsor ID
- 6308 (FH/UWCC ID)
- Conditions
- Male Breast Cancer, Recurrent Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2005 (actual)
- Primary completion
- Apr 2010 (actual)
- First posted
- 23 Jan 2007 (estimated)
- Results
- Posted 4 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: ONTAK may be able to help reduce the type of cells that prevent other types of immune cells from attacking the breast cancer cells.
PURPOSE: This phase I/II trial is studying the safety of ONTAK and its possible side effects to see how well it works in treating patients with advanced breast cancer that did not respond to previous treatment.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety of ONTAK infusion in patients with advanced refractory breast cancer.
II. To evaluate the effect of ONTAK administration on peripheral blood T-regulatory cells.
SECONDARY OBJECTIVES:
- To evaluate the incidence of IL-2R expression in tumor samples and investigate the correlation of tumor IL-2R expression and tumor response to ONTAK therapy.
II. To evaluate levels of circulating sIL-2R before and after ONTAK therapy. III. To evaluate the effect of ONTAK on endogenous tumor specific immunity. IV. To evaluate the potential anti-tumor effects of ONTAK in patients with advanced refractory breast cancer.
OUTLINE:
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: ONTAK, Other: flow cytometry, Other: immunohistochemistry staining method, Other: enzyme-linked immunosorbent assay, Other: laboratory biomarker analysis, Genetic: protein expression analysisPatients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with advanced stage refractory breast cancer
- Progressive or relapsed disease following standard therapy
- Patients must have measurable disease that can include, but is not limited to bone; specifically, patients must have measurable extraskeletal disease that can be accurately measured in at least one dimension as >= 20 mm with conventional CT techniques or >= 10 mm with spiral CT scan; measurable (bi-dimensional) chest wall disease will also be allowed
- Patients must be at least 14 days out from last cytotoxic chemotherapy; patients on bisphosphonates are eligible
- White blood cell count (WBC) > 3.0 THOU/ul
Key exclusion criteria (6 listed)
- Prior treatment with ONTAK (DAB389 IL-2) or DAB486 IL-2
- Known history of hypersensitivity to diphtheria toxin or IL-2
- Active autoimmune disease
- Known history of pulmonary disease except controlled asthma
- History of or pre-existing, cardiovascular disease as defined by New York Heart Association (NYHA) Class III-IV categorization
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 |
|---|---|---|
| ONTAKAlso: DAB389 interleukin-2, DAB389 interleukin-2 immunotoxin, DAB389-IL2, DAB389IL-2Given IV | Biological | Arm I |
| flow cytometryCorrelative studies | Other | Arm I |
| immunohistochemistry staining methodAlso: immunohistochemistryCorrelative studies | Other | Arm I |
| enzyme-linked immunosorbent assayAlso: ELISACorrelative studies | Other | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
| protein expression analysisCorrelative studies | Genetic | Arm I |
Primary outcome
Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0
Time frame: 7 Days after last dose of ONTAK
Subjects are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, serum albumin, complete blood counts, symptom assessment, and physical exams performed at every cycle until 3 weeks after the final dose of ONTAK. All adverse events for all systems are graded on a scale of 1-5 using CTCAE v3.0.
Efficacy of ONTAK in Depleting T-regulatory Cells as a Decrease in Peripheral Blood Tregs Using Flow Cytometry
Time frame: 21 days after cycle 6
The efficacy of ONTAK in depleting Tregs will be defined as a decrease in peripheral blood Tregs by 25% of each individual subject's baseline. All subjects will undergo blood draws at baseline and post ONTAK infusions at designated time points. Tregs from the peripheral blood will be quantitated using flow cytometry.
4 secondary outcomes
Incidence of Interleukin-2 (IL-2) and IL-2 Receptor (IL-2R) Expression in Tumor Samples by Immunohistochemical (IHC) Analysis
Time frame: 21 days after cycle 6
Presence of Circulating sIL-2R in the Peripheral Blood
Time frame: 21 days after cycle 6
Presence of Endogenous Tumor-specific Immunity
Time frame: 21 days after cycle 6
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
Time frame: 21 days after cycle 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2018.
- 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.
Lupe Salazar principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ONTAK, flow cytometry and immunohistochemistry staining method in people with Male Breast Cancer and Recurrent Breast Cancer, run by University of Washington 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 14 inclusion and 6 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: finished, as of the sponsor's last update on 5 Dec 2018. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 4 Aug 2017). 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?
Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0 (time frame: 7 Days after last dose of ONTAK). The study lists 2 primary outcomes in all. 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 5 Dec 2018.