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Breast CancerPhase 1NCT03285607

MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer

A Phase 1 study testing MCS110, Doxorubicin and Cyclophosphamide in people with Breast Cancer and Cancer of Breast, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

In patients with locally advanced hormone receptor positive (HR+)/HER2- breast cancer, neoadjuvant chemotherapy produces a pathologic complete response rate (pCR) of only 9-15%, and late recurrences often occur despite neoadjuvant chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Cancer of Breast
What is being tested?
MCS110, Doxorubicin and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Sep 2018to 28 Feb 2021
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically or cytologically confirmed ER+ HER2- breast cancer. ER-positivity is to follow local guidelines. If IHC HER2 is 2+, a negative FISH test is required.
  • Clinical stage II or stage III (by AJCC 7th edition) breast cancer eligible for neoadjuvant chemotherapy with complete surgical excision of the breast cancer after neoadjuvant therapy as the treatment goal.
  • Clinically positive axillary lymph nodes.
  • At least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Normal bone marrow and organ function as defined below:
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  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Creatinine ≤ 1.5 x IULN
  • PT/INR ≤ 1.5 x IULN (for participants on anticoagulation therapy, ≤ 1.5 x baseline value)
  • aPTT ≤ 1.5 x IULN (for participants on anticoagulation therapy, ≤ 1.5 x baseline value)
  • Adequate cardiac function as defined below:
  • LVEF ≥ 50%
  • QTC ≤ 470 msec for females and ≤ 450 msec for males
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose of MCS110. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 month after completion of MCS110 administration.
  • Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • Presence of metastatic disease.
  • Therapy for underlying malignancy within 2 weeks prior to start of study treatment.
  • A history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  • Bilateral or inflammatory breast cancer.
  • Currently receiving any other investigational agents.
  • Receiving immunosuppressive agents or > 10 mg daily prednisone or equivalent of corticosteroids.
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  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MCS110, doxorubicin, cyclophosphamide, paclitaxel, or other agents used in the study.
  • Known hypersensitivity to monoclonal antibodies.
  • Personal or family history of long QT syndrome.
  • Evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment / central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration.
  • Diagnosis of any type of muscle disease that may result in CK elevation.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Clinically significant cardiovascular disease within 6 months of screening.
  • Presence of any Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater toxicity.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
  • Known history of human immunodeficiency virus or infection with hepatitis requiring antiviral therapy.

About this study

Official title: Phase I Study of MCS110 Combined With Neoadjuvant Dose-Dense Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer

In patients with locally advanced hormone receptor positive (HR+)/HER2- breast cancer, neoadjuvant chemotherapy produces a pathologic complete response rate (pCR) of only 9-15%, and late recurrences often occur despite neoadjuvant chemotherapy. Therefore, there is an unmet clinical need to improve the outcomes of these patients. Tumor-associated macrophages (TAM) infiltration leads to poor outcomes in breast cancer patients by promoting angiogenesis, activating epithelial-mesenchymal transition, degrading the extracellular matrix, and suppressing the anti-tumor immune response. Pre-clinical studies, as summarized above, have shown that the breast cancer immune microenvironment may be reprogrammed by targeting colony-stimulating factor-1 (CSF-1) to decrease TAM infiltration and increase CD8+ TIL infiltration, in order to foster antitumor immunity and improve response to therapy.

Here, the investigators propose a phase I dose-escalation study in patients with locally advanced HR+/HER2- breast cancer to determine the feasibility of adding MCS110, a CSF-1 inhibitor, to the standard neoadjuvant chemotherapy regimen of dose-dense doxorubicin, cyclophosphamide followed by paclitaxel. The investigators will also include a dose expansion cohort for preliminary efficacy analysis and correlative studies. The investigators propose that if they can decrease the TAM-induced immunosuppression and TAM-induced chemoresistance observed in breast cancer patients, then the patients' own immune system could find and destroy the dormant and resistant tumor cells, and combined with enhanced chemotherapy efficacy, the investigators will see durable remissions and long term cures.

Being tested
MCS110, Doxorubicin, Cyclophosphamide, Paclitaxel, Bone marrow aspirate
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MCS110Biological

    -MCS110 is an IgG1/κ humanized monoclonal antibody directed against human macrophage colony stimulating factor

  • DoxorubicinDrug

    Also called Adriamycin®

    -Standard of care

  • CyclophosphamideDrug

    Also called Cytoxan, CPM, CTX, CYT

    -Standard of care

  • PaclitaxelDrug

    Also called Taxol

    -Standard of care

  • Bone marrow aspirateProcedure or surgery

    -Time of enrollment and at time of surgery

  • Peripheral blood samplesProcedure or surgery

    -Time of enrollment and at time of surgery

  • Tumor tissueProcedure or surgery

    -Time of enrollment and at time of surgery

Study groups in NCT03285607
Study groupRoleWhat they receive
Dose Level 1:MCS110/Doxorubicin/Cyclophosphamide/PaclitaxelExperimental* MCS110 will be administered intravenously over 60 minutes (up to 120 minutes permitted) on a 28-day cycle. The dose of MCS110 given will depend on the dose level to which a given patient is enrolled. * The standard neoadjuvant chemotherapy regimen of dose-dense doxorubicin/ cyclophosphamide followed by weekly paclitaxel consists of: * doxorubicin 60 mg/m^2 IV Q2W during Weeks 1 through 8 (total of 4 doses) * cyclophosphamide 600 mg/m^2 Q2W during Weeks 1 through 8 (total of 4 doses) * paclitaxel 80 mg/m^2 IV QW during Weeks 9 through 20 (total of 12 doses) * Surgery will be performed approximately 4-6 weeks after the end of the last cycle of treatment (Week 20-22). It is outside the scope of this study as part of each patient's standard of care. Both types of surgery (lumpectomy or mastectomy) are allowed. The decision on surgical approach and timing will be at the discretion of the treating surgeon.
Receives: Biological: MCS110; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Procedure: Bone marrow aspirate; Procedure: Peripheral blood samples; Procedure: Tumor tissue
Dose Level 2:MCS110/Doxorubicin/Cyclophosphamide/PaclitaxelExperimental* MCS110 will be administered intravenously over 60 minutes (up to 120 minutes permitted) on a 28-day cycle. The dose of MCS110 given will depend on the dose level to which a given patient is enrolled. * The standard neoadjuvant chemotherapy regimen of dose-dense doxorubicin/ cyclophosphamide followed by weekly paclitaxel consists of: * doxorubicin 60 mg/m^2 IV Q2W during Weeks 1 through 8 (total of 4 doses) * cyclophosphamide 600 mg/m^2 Q2W during Weeks 1 through 8 (total of 4 doses) * paclitaxel 80 mg/m^2 IV QW during Weeks 9 through 20 (total of 12 doses) * Surgery will be performed approximately 4-6 weeks after the end of the last cycle of treatment (Week 20-22). It is outside the scope of this study as part of each patient's standard of care. Both types of surgery (lumpectomy or mastectomy) are allowed. The decision on surgical approach and timing will be at the discretion of the treating surgeon.
Receives: Biological: MCS110; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Procedure: Bone marrow aspirate; Procedure: Peripheral blood samples; Procedure: Tumor tissue
Dose Expansion:MCS110/Doxorubicin/Cyclophosphamide/PaclitaxelExperimental* MCS110 will be administered intravenously over 60 minutes (up to 120 minutes permitted) on a 28-day cycle. The dose of MCS110 given will depend on the dose level to which a given patient is enrolled. * The standard neoadjuvant chemotherapy regimen of dose-dense doxorubicin/ cyclophosphamide followed by weekly paclitaxel consists of: * doxorubicin 60 mg/m^2 IV Q2W during Weeks 1 through 8 (total of 4 doses) * cyclophosphamide 600 mg/m^2 Q2W during Weeks 1 through 8 (total of 4 doses) * paclitaxel 80 mg/m^2 IV QW during Weeks 9 through 20 (total of 12 doses) * Surgery will be performed approximately 4-6 weeks after the end of the last cycle of treatment (Week 20-22). It is outside the scope of this study as part of each patient's standard of care. Both types of surgery (lumpectomy or mastectomy) are allowed. The decision on surgical approach and timing will be at the discretion of the treating surgeon.
Receives: Biological: MCS110; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Procedure: Bone marrow aspirate; Procedure: Peripheral blood samples; Procedure: Tumor tissue

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD) of regimen

    • The maximum tolerated dose (MTD) is defined as the dose level at which <1 patients of a cohort (of 3 to 6 patients) experience dose-limiting toxicity during the first cycle.
    • A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of CTCAE Grade ≥ 3 assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle of treatment with the combination treatment and meets any of the criteria outlined.

    Measured: Completion of cycle 1 (28 days) for all patients

Secondary outcomes (4)

  1. Safety and tolerability of regimen as measured by grade and number of adverse events experienced per participant

    -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

    Measured: 30 days after completion of treatment (approximately 24 weeks)

  2. Pathologic complete response-rate (pCR)

    -Pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes. All eligible patients who have completed neoadjuvant therapy and have subsequently undergone surgery are included in the analysis of pCR.

    Measured: At the time of surgery (approximately 20 weeks)

  3. Residual invasive tumor size (RITS)

    -Residual invasive tumor size (RITS) is histopathologically assessed by the largest dimension of the dominant invasive tumor focus from the surgical specimen. In cases in which there was no residual invasive tumor, the RITS will be 0 mm. In cases in which multifocal pathology is present, the largest dimension of the residual invasive tumor focus will be recorded.

    Measured: At the time of surgery (approximately 20 weeks)

  4. Number of positive axillary lymph nodes

    -Number of positive axillary lymph nodes is defined as number of resected lymph nodes with axillary nodal micrometastases (>0.2-<2 mm) or overt metastases (⩾2 mm).

    Measured: At the time of surgery (approximately 20 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2017
  2. Study start30 Sep 2018 (estimated)
  3. Primary completion31 Oct 2019 (estimated)
  4. Study completion28 Feb 2021 (estimated)

Why it stopped: Drug provider decided not to move forward with the study.

Resources

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03285607
Sponsor's protocol ID
201711073
Other IDs
MCS110ZUS02T
Status last verified
Aug 2018
First submitted
14 Sep 2017
Last updated
16 Aug 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MCS110, Doxorubicin and Cyclophosphamide in people with Breast Cancer and Cancer of Breast, run by Washington University School of Medicine.

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 19 inclusion and 15 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: withdrawn, as of the sponsor's last update on 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Maximum tolerated dose (MTD) of regimen (time frame: Completion of cycle 1 (28 days) for all patients). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03285607.

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 16 Aug 2018; AzTrials last refreshed its copy on 6 Nov 2026.

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