A Phase 1 interventional study of MCS110 and Doxorubicin in Breast Cancer and Cancer of Breast, sponsored by Washington University School of Medicine. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-08-16.
Sponsored by Washington University School of Medicine · Phase 1, Interventional, and Treatment
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.
Normal bone marrow and organ function as defined below:
Adequate cardiac function as defined below:
Exclusion Criteria:
* 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.
Biological: MCS110 · Drug: Doxorubicin · Drug: Cyclophosphamide · Drug: Paclitaxel · Procedure: Bone marrow aspirate · Procedure: Peripheral blood samples · Procedure: Tumor tissue
* 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.
Biological: MCS110 · Drug: Doxorubicin · Drug: Cyclophosphamide · Drug: Paclitaxel · Procedure: Bone marrow aspirate · Procedure: Peripheral blood samples · Procedure: Tumor tissue
* 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.
Biological: MCS110 · Drug: Doxorubicin · Drug: Cyclophosphamide · Drug: Paclitaxel · Procedure: Bone marrow aspirate · Procedure: Peripheral blood samples · Procedure: Tumor tissue
-MCS110 is an IgG1/κ humanized monoclonal antibody directed against human macrophage colony stimulating factor
-Standard of care
Also known as: Adriamycin®
-Standard of care
Also known as: Cytoxan, CPM, CTX, CYT
-Standard of care
Also known as: Taxol
-Time of enrollment and at time of surgery
-Time of enrollment and at time of surgery
-Time of enrollment and at time of surgery
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.
Time frame: Completion of cycle 1 (28 days) for all patients
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.
Time frame: 30 days after completion of treatment (approximately 24 weeks)
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.
Time frame: At the time of surgery (approximately 20 weeks)
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.
Time frame: At the time of surgery (approximately 20 weeks)
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).
Time frame: At the time of surgery (approximately 20 weeks)
No study locations are listed for this record.
Plan to share: No
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Washington University School of Medicine