Pilot Study of Glembatumumab Vedotin Following Doxorubicin and Cytoxan as Neo-adjuvant Therapy in Gp-NMB-expressing High Risk Triple Negative Breast Cancer

NCT03473691 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: TBDBreast50
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single arm, pilot study assessing safety/feasibility and efficacy of neo-adjuvant glembatumumab vedotin (GV) in patients with high risk triple negative breast cancer (TNBC) with glycoprotein-NMB (gpNMB) expression ≥ 25%. Primary endpoints will be safety/feasibility, and secondary endpoints will be rates of pathologic complete response (pCR), and measurements of growth differentiation factor-11 (GDF11) and glycoprotein NMB (gpNMB) expression.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Incidence of Adverse Events (AEs)

  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).

  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

  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 Outcomes (3)

• Efficacy

  3-6 weeks after last GV infusion for each patient

• Growth Differentiation Factor-11 (GDF11) expression in the tumor

  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

  Prior to therapy (in the 28 days prior to starting study treatment) and 3-6 weeks after last GV infusion for each patient

Other Outcomes (1)

• Peripheral circulating CD8 and CD4 T cell ratio

  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).

Study Arms (1)

Glembatumumab vedotin (GV)

EXPERIMENTAL

Drug: Glembatumumab Vedotin

Interventions

Glembatumumab Vedotin DRUG

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.

Also known as: CDX-011

Glembatumumab vedotin (GV)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL\]

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead
• Celldex Therapeutics: collaborator

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

glembatumumab vedotin

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Patrick Dillon, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: March 22, 2018
• Study Start: May 1, 2018
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: December 9, 2024

Record last verified: 2024-12