- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03473691
Pilot Study of Glembatumumab Vedotin Following Doxorubicin and Cytoxan as Neo-adjuvant Therapy in Gp-NMB-expressing High Risk Triple Negative Breast Cancer (Breast50)
Pilot Study of the Antibody-drug Conjugate Glembatumumab Vedotin (CDX-011) Following Doxorubicin (Adriamycin) and Cytoxan as Neo-adjuvant Therapy in Glycoprotein NMB-expressing High Risk Triple Negative Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Phase
- Early Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator.
- Patients diagnosed with triple negative breast cancer, (stages II-III, or high risk T1c disease) found to have gpNMB expression at or above 25%), and who are appropriate candidates for neo-adjuvant therapy. Patients must be willing to undergo lumpectomy (with radiation therapy) or mastectomy following neo-adjuvant therapy.
- Subjects may be female or male.
- ECOG Performance Status of 0-2.
- Age ≥ 18 years.
- Subject must have a life expectancy ≥ 6 months.
- Absolute neutrophil count ≥ 1,500 cells/mm3
- Platelets ≥ 100,000 cells/mm3
- Hemoglobin ≥ 9g/dl (Note: The use of transfusion to achieve Hemoglobin ≥ 9 g/dl is acceptable)
- Serum creatinine OR GFR ≤ 1.5 x institutional upper limit normal (IULN)
- Bilirubin ≤ 1.5 x IULN OR Direct Bilirubin ≤ULN for patients with total bilirubin levels >1.5×ULN
- ALT and AST ≤ 2.5 IULN
- Alkaline phosphatase ≤ 2.5 IULN
Women of childbearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for at least 1 year following last dose of study drug.
a. WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL]
i. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and for at least 1 year following participation and the potential risk factors for an unintentional pregnancy
ii. The following birth control methods are allowed during the study: Barrier methods (Intra-uterine device (IUD), Diaphragm with spermicide, Cervical cap with spermicide, Condom with spermicide) or Abstinence (no heterosexual activity)
b. Non-vasectomized males must agree to use adequate contraception for at least 120 days after the last dose of study drug
i.The following birth control methods are allowed during the study: Partner is not WOCBP or is taking hormonal contraceptives, Barrier methods (Intra-uterine device (IUD), Diaphragm with spermicide, Cervical cap with spermicide, Condom with spermicide) or Abstinence (no heterosexual activity)
ii. Males must also abstain from sperm donations for at least 120 days after the last dose of study drug
Exclusion Criteria:
- Patients that have received more than one cycle of neo-adjuvant doxorubicin and cyclophosphamide prior to enrolling on the study.*
- Prior radiation therapy for this breast cancer. Prior radiation for other malignancy must have been completed >12 weeks prior to on-study date.
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible.
- Subjects who are receiving any investigational agents or have had any investigational agent within the 30 days prior to on-study date
- Subjects who are unable or unwilling to discontinue use of prohibited medications including long-term use of systemic corticosteroids (equivalent to ≥ 10 mg prednisone for ≥1 month within 1 month of study enrollment).
- Subject is unable or unwilling to participate in a study related procedure
- Pregnant and breastfeeding women. See Pre-Study Assessments section for more information on pregnancy tests.
- Subject is a prisoner
- Subjects with known acute hepatitis, human immunodeficiency virus (HIV) or active infections that require parenteral antibiotics.
- Significant history of uncontrolled cardiac disease defined as uncontrolled hypertension, unstable angina, or myocardial infarction within the last 4 months, and uncontrolled congestive heart failure.
- A serious uncontrolled medical disorder that in the opinion of the Investigator would impair the ability of the subject to receive protocol therapy.
- Subjects with history of or evidence upon physical examination of central nervous system disease including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within six months of study entry.
- Baseline neuropathy > grade 2
- Subjects with a known history of immunogenic response or allergic reactions attributed to compounds of similar chemical composition to dolastatin or auristatin
- Abnormal cardiac function, defined as a left ventricular ejection fraction (LVEF) < 50% by echocardiogram (ECHO) or multigated acquisition scan (MUGA) * If a patient has undergone one cycle of chemotherapy, he or she must have recovered from all adverse events to ≤ grade 1 to meet the above inclusion criteria. Labs collected prior to initiation of AC treatment may be used for eligibility, as long as they are collected in the required 28 day window. Patients that have received one cycle of AC prior to enrollment will receive 3 additional cycles of AC to complete a total of 4 cycles prior to starting GV.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Glembatumumab vedotin (GV)
|
Standard neo-adjuvant dose-dense doxorubicin 60 mg/m2 and Cytoxan 600 mg/m2 IV every 14 days for 4 cycles followed by GV 1.9 mg/kg IV every 21 days for 4 cycles.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events (AEs)
Time Frame: Adverse events will be assessed from the time of consent through 30 days after participants complete GV treatment (unless study treatment is stopped for safety or investigator or participant decision, study treatment will last 25-28 weeks)
|
Adverse events will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
|
Adverse events will be assessed from the time of consent through 30 days after participants complete GV treatment (unless study treatment is stopped for safety or investigator or participant decision, study treatment will last 25-28 weeks)
|
Proportion of patients who complete the 4 cycles of GV within 15 weeks of the first dose of GV (without dose limiting adverse events).
Time Frame: Within 4 months of the last patient enrollment
|
To assess feasibility, the proportion of patients who receive the intended dose within 15 weeks of the first dose will be estimated with an 80% confidence interval.
|
Within 4 months of the last patient enrollment
|
Number of discontinuations due to AEs
Time Frame: During each participant's study treatment. Unless study treatment is stopped for safety or investigator or participant decision, study treatment will last about 22 weeks.
|
Adverse events will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Participants that discontinue study treatment because of AEs based on protocol-defined stopping rules will be included.
|
During each participant's study treatment. Unless study treatment is stopped for safety or investigator or participant decision, study treatment will last about 22 weeks.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy
Time Frame: 3-6 weeks after last GV infusion for each patient
|
Rates of pathologic complete response (pCR) following GV therapy
|
3-6 weeks after last GV infusion for each patient
|
Growth Differentiation Factor-11 (GDF11) expression in the tumor
Time Frame: Prior to therapy (in the 28 days prior to starting study treatment) and 3-6 weeks after last GV infusion for each patient.
|
GDF11 expression by immunohistochemistry prior to and following doxorubicin/cyclophosphamide and GV therapy
|
Prior to therapy (in the 28 days prior to starting study treatment) and 3-6 weeks after last GV infusion for each patient.
|
Glycoprotein-NMB (gpNMB) expression in the tumor
Time Frame: Prior to therapy (in the 28 days prior to starting study treatment) and 3-6 weeks after last GV infusion for each patient
|
gpNMB expression by immunohistochemistry prior to and following doxorubicin/cyclophosphamide and GV therapy
|
Prior to therapy (in the 28 days prior to starting study treatment) and 3-6 weeks after last GV infusion for each patient
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Peripheral circulating CD8 and CD4 T cell ratio
Time Frame: Prior to therapy (in the 28 days prior to starting study treatment) and at the last treatment with GV (about 22 weeks after starting study treatment).
|
Blood will be collected in order to assess the proportions of CD8 and CD4 t cells.
|
Prior to therapy (in the 28 days prior to starting study treatment) and at the last treatment with GV (about 22 weeks after starting study treatment).
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TBDBreast50
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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