Breast CancerPhase 2NCT00824733
Agatolimod and Trastuzumab in Treating Patients With Locally Advanced or Metastatic Breast Cancer
A Phase 2 study testing Trastuzumab, PF03512676 and Correlative Studies in people with Breast Cancer, run by Bhuvaneswari Ramaswamy at 1 site in United States.
Trial summary
RATIONALE: Biological therapies, such as agatolimod, may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Trastuzumab, PF03512676 and Correlative Studies
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Apr 2014
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed breast cancer
- Locally advanced or metastatic disease
- HER2-overexpressing tumor, defined as 3+ overexpression by IHC and/or HER2 amplified by FISH
- Non-measurable disease allowed
- Achieved partial response, complete response, or stable disease (i.e., no disease progression for ≥ 12 weeks) while on trastuzumab (Herceptin®) and chemotherapy, hormonal therapy alone, or trastuzumab alone
- Last dose of trastuzumab must have been administered within the past 16 weeks
- No unstable brain metastases
- Patients with brain metastases are eligible provided they have been stable for ≥ 1 month after surgery or radiotherapy/radiosurgery AND off corticosteroids and anticonvulsants for ≥ 4 weeks
- Hormone receptor status unspecified
PATIENT CHARACTERISTICS:
- ECOG(Eastern Cooperative Oncology Group)performance status (PS) 0-2 (Karnofsky PS 70-100%)
- Absolute neutrophil count ≥ 1,500/mm³
- Hemoglobin > 8 g/dL (transfusion/epoetin alfa allowed)
- Platelet count ≥ 100,000/mm³
- Total bilirubin < 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if known liver metastases)
- Creatinine < 2 mg/mL
- Ejection fraction ≥ 50% by echocardiogram or MUGA
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception before, during, and for ≥ 3 months after completion of study treatment
- No ongoing or active infection requiring oral or IV antibiotics
- No known autoimmune disorders or antibody-mediated disorders
- No known HIV positivity
- No known history of hepatitis B or C (active and/or previously treated)
- No other malignancies within the past 5 years except nonmelanoma skin cancer or cervical cancer in situ
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 12 weeks since prior chloroquine
- More than 4 weeks since prior growth factors
- More than 4 weeks since prior systemic corticosteroids
- More than 4 weeks since prior chemotherapy, radiotherapy, or monoclonal antibody therapy (except trastuzumab)
- No prior agatolimod sodium
- No prior allogeneic stem cell transplantation
- No prior continuous treatment with single-agent trastuzumab for > 6 months
- No more than 3 prior chemotherapy regimens for metastatic breast cancer
- Any number of prior hormonal therapies allowed
- No other concurrent investigational agents or monoclonal antibodies
- No other concurrent anticancer agents or therapies
- Concurrent bisphosphonates for skeletal metastasis allowed
Trial locations and contacts
1 site in 1 country.
United States1 site
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
About this study
Official title: A Phase II Open-label Study of Subcutaneous CPG ODN (PF03512676) in Combination With Trastuzumab in Patients With Metastatic Breast Cancer
RATIONALE: Biological therapies, such as agatolimod, may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving agatolimod together with trastuzumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving agatolimod together with trastuzumab works in treating patients with locally advanced or metastatic breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate the progression-free survival of patients with HER2-overexpressing locally advanced or metastatic breast cancer treated with trastuzumab (Herceptin®) and agatolimod sodium.
Secondary
- To determine if agatolimod sodium augments antibody-mediated cytoxicity (ADCC) against trastuzumab-coated target cells by evaluating the ability of patient immune-effector cells to conduct ADCC and produce interferon gamma.
OUTLINE: This is a multicenter study.
Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Patients also receive agatolimod sodium subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for correlative laboratory studies. Samples are analyzed for antibody-mediated cytotoxicity (ADCC) by chromium-release assay; IFN-γ production and quantification by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR); and levels of cytokines (IFN-γ and TNF-α) by ELISA.
After completion of study therapy, patients are followed periodically.
- Conditions
- Breast Cancer
- Being tested
- Trastuzumab, PF03512676, Correlative Studies
- Keywords
- recurrent breast cancer, stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, HER2-positive breast cancer, male breast cancer
- Medical subject headings
- Breast Neoplasms, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin
IV at 2 mg/kg over 30 minutes on day 1 of each weekly cycle. Patients who have not received trastuzumab for 4 weeks or more will receive a loading dose of 4 mg/kg over 90 minutes day 1 of the first cycle. The dose of trastuzumab will be based on the patient's actual weight at the start of each 4 week treatment cycle.
PF03512676Drug
Also called agatolimod sodium
Patients also receive PF03512676 subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses.
Correlative StudiesOther
Blood for performing the correlative studies will be drawn on week 1, 2, 6, 12 and 18.
| Study group | Role | What they receive |
|---|---|---|
| Arm I: Treatment (PF03512676 in combination with Trastuzumab) | Experimental | 12 weekly treatments. Week 1-12 patients will receive Trastuzumab 2mg/kg IV(intervenous infusion). Patients who have not been treated wih Trastuzumab within 4 weeks will receive a loading dose of 4 mg/kg on week 1 and PF-03512676-0.16 mg/kg subcutaneous injection.Correlative studies will be drawn on week 1, 2, 6, 12 and 18. Receives: Drug: Trastuzumab; Drug: PF03512676; Other: Correlative Studies |
What is being measured
The primary outcome is the main question the study is designed to answer.
PF-03512676 Augments Antibody Mediated Cytoxicity (ADCC)Against Trastuzumab-coated Target Cells in Metastatic HER2 Overexpressing Breast Cancer.
Measured: up to 18 weeks
Secondary outcomes (2)
Progression-free Survival for Patients With Metastatic Breast Cancer That Are Receiving Trastuzumab Plus PF-03512676
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 lesions
Measured: up to 18 weeks
Combination of PF-03512676 and Trastuzumab Induces MIP-1 (Macrophage Inflammatory Protein 1), MCP-1 (Monocyte Chemoattract Protein 1) and RANTES.
Measured: up to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2009 (estimated)
- Study startFeb 2009
- Primary completionFeb 2013
- Study completionApr 2014
Why it stopped: Inaccurate patient accrual for trial
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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bhuvaneswari Ramaswamy
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor-investigator, Bhuvaneswari Ramaswamy, Ohio State University Comprehensive Cancer Center
- Investigators
- Bhuvaneswari Ramaswamy, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00824733
- Sponsor's protocol ID
- OSU-08153
- Other IDs
- NCI-2011-03157
- Status last verified
- Dec 2015
- First submitted
- 16 Jan 2009
- Last updated
- 14 Jan 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 14 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-label Study of Subcutaneous CPG ODN (PF03512676) in Combination With Trastuzumab in Patients With Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00824733
- Acronym / sponsor ID
- OSU-08153
- Conditions
- Breast Cancer
- Keywords
- recurrent breast cancer, stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, HER2-positive breast cancer, male breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inaccurate patient accrual for trial
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Bhuvaneswari RamaswamyUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Feb 2009
- Primary completion
- Feb 2013 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 19 Jan 2009 (estimated)
- Results
- Posted 14 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Biological therapies, such as agatolimod, may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving agatolimod together with trastuzumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving agatolimod together with trastuzumab works in treating patients with locally advanced or metastatic breast cancer.
Detailed description
OBJECTIVES:
Primary
- To evaluate the progression-free survival of patients with HER2-overexpressing locally advanced or metastatic breast cancer treated with trastuzumab (Herceptin®) and agatolimod sodium.
Secondary
- To determine if agatolimod sodium augments antibody-mediated cytoxicity (ADCC) against trastuzumab-coated target cells by evaluating the ability of patient immune-effector cells to conduct ADCC and produce interferon gamma.
OUTLINE: This is a multicenter study.
Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Patients also receive agatolimod sodium subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for correlative laboratory studies. Samples are analyzed for antibody-mediated cytotoxicity (ADCC) by chromium-release assay; IFN-γ production and quantification by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR); and levels of cytokines (IFN-γ and TNF-α) by ELISA.
After completion of study therapy, patients are followed periodically.
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: Treatment (PF03512676 in combination with Trastuzumab) | Experimental | Drug: Trastuzumab, Drug: PF03512676, Other: Correlative Studies12 weekly treatments. Week 1-12 patients will receive Trastuzumab 2mg/kg IV(intervenous infusion). Patients who have not been treated wih Trastuzumab within 4 weeks will receive a loading dose of 4 mg/kg on week 1 and PF-03512676-0.16 mg/kg subcutaneous injection.Correlative studies will be drawn on week 1, 2, 6, 12 and 18. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- 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 |
|---|---|---|
| TrastuzumabAlso: HerceptinIV at 2 mg/kg over 30 minutes on day 1 of each weekly cycle. Patients who have not received trastuzumab for 4 weeks or more will receive a loading dose of 4 mg/kg over 90 minutes day 1 of the first cycle. The dose of trastuzumab will be based on the patient's actual weight at the start of each 4 week treatment cycle. | Drug | Arm I: Treatment (PF03512676 in combination with Trastuzumab) |
| PF03512676Also: agatolimod sodiumPatients also receive PF03512676 subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses. | Drug | Arm I: Treatment (PF03512676 in combination with Trastuzumab) |
| Correlative StudiesBlood for performing the correlative studies will be drawn on week 1, 2, 6, 12 and 18. | Other | Arm I: Treatment (PF03512676 in combination with Trastuzumab) |
Primary outcome
PF-03512676 Augments Antibody Mediated Cytoxicity (ADCC)Against Trastuzumab-coated Target Cells in Metastatic HER2 Overexpressing Breast Cancer.
Time frame: up to 18 weeks
2 secondary outcomes
Progression-free Survival for Patients With Metastatic Breast Cancer That Are Receiving Trastuzumab Plus PF-03512676
Time frame: up to 18 weeks
Combination of PF-03512676 and Trastuzumab Induces MIP-1 (Macrophage Inflammatory Protein 1), MCP-1 (Monocyte Chemoattract Protein 1) and RANTES.
Time frame: up to 18 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- JameslineLink provided by the sponsor.
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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.
Bhuvaneswari Ramaswamy, MD principal investigator
Ohio State University Comprehensive Cancer Center
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 Trastuzumab, PF03512676 and Correlative Studies in people with Breast Cancer, run by Bhuvaneswari Ramaswamy 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 14 Jan 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 14 Jan 2016). 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?
PF-03512676 Augments Antibody Mediated Cytoxicity (ADCC)Against Trastuzumab-coated Target Cells in Metastatic HER2 Overexpressing Breast Cancer. (time frame: up to 18 weeks). 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 14 Jan 2016.