Overview

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

Status:
Withdrawn
Trial end date:
2018-05-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Early Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Virginia
Collaborator:
Celldex Therapeutics
Treatments:
Antibodies, Monoclonal
Cyclophosphamide
Doxorubicin
Glembatumumab vedotin
Liposomal doxorubicin
Criteria
Inclusion Criteria:

1. Willingness and ability to provide written informed consent and to comply with the
study protocol as judged by the investigator.

2. 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.

3. Subjects may be female or male.

4. ECOG Performance Status of 0-2.

5. Age ≥ 18 years.

6. Subject must have a life expectancy ≥ 6 months.

7. Absolute neutrophil count ≥ 1,500 cells/mm3

8. Platelets ≥ 100,000 cells/mm3

9. Hemoglobin ≥ 9g/dl (Note: The use of transfusion to achieve Hemoglobin ≥ 9 g/dl is
acceptable)

10. Serum creatinine OR GFR ≤ 1.5 x institutional upper limit normal (IULN)

11. Bilirubin ≤ 1.5 x IULN OR Direct Bilirubin ≤ULN for patients with total bilirubin
levels >1.5×ULN

12. ALT and AST ≤ 2.5 IULN

13. Alkaline phosphatase ≤ 2.5 IULN

14. 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:

1. Patients that have received more than one cycle of neo-adjuvant doxorubicin and
cyclophosphamide prior to enrolling on the study.*

2. Prior radiation therapy for this breast cancer. Prior radiation for other malignancy
must have been completed >12 weeks prior to on-study date.

3. 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.

4. Subjects who are receiving any investigational agents or have had any investigational
agent within the 30 days prior to on-study date

5. 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).

6. Subject is unable or unwilling to participate in a study related procedure

7. Pregnant and breastfeeding women. See Pre-Study Assessments section for more
information on pregnancy tests.

8. Subject is a prisoner

9. Subjects with known acute hepatitis, human immunodeficiency virus (HIV) or active
infections that require parenteral antibiotics.

10. 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.

11. A serious uncontrolled medical disorder that in the opinion of the Investigator would
impair the ability of the subject to receive protocol therapy.

12. 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.

13. Baseline neuropathy > grade 2

14. Subjects with a known history of immunogenic response or allergic reactions attributed
to compounds of similar chemical composition to dolastatin or auristatin

15. 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.