Triple Negative Breast CancerEarly Phase 1Breast50NCT03473691

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

A Early Phase 1 study testing Glembatumumab Vedotin in people with Triple Negative Breast Cancer, run by University of Virginia.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Triple Negative Breast Cancer
What is being tested?: Glembatumumab Vedotin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: 1 May 2018to 1 May 2018
Phase: Early 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

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.

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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.
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]
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
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)
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)
Males must also abstain from sperm donations for at least 120 days after the last dose of study drug

Who cannot join

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

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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.

About this study

Official title: 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

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.

Read the detailed description

Patients will receive neo-adjuvant dose-dense (DD) doxorubicin (Adriamycin)/cyclophosphamide (AC) followed by GV. After completion of neo-adjuvant therapy, all patients will undergo lumpectomy (with radiation therapy) or mastectomy, and tissue will be assessed for residual disease to determine rates of pCR. Tumor tissue will be obtained by core needle biopsy and at the time of surgery for use in the correlative studies.

Conditions: Triple Negative Breast Cancer
Being tested: Glembatumumab Vedotin
Medical subject headings: Triple Negative Breast Neoplasms

What participants receive

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

Glembatumumab VedotinDrug
Also called CDX-011
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.

Study groups in NCT03473691
Study group	Role	What they receive
Glembatumumab vedotin (GV)	Experimental	Not described Receives: Drug: Glembatumumab Vedotin

What is being measured

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

Incidence of Adverse Events (AEs)
Adverse events will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Measured: 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.
Measured: 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.
Measured: 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
Rates of pathologic complete response (pCR) following GV therapy
Measured: 3-6 weeks after last GV infusion for each patient
Growth Differentiation Factor-11 (GDF11) expression in the tumor
GDF11 expression by immunohistochemistry prior to and following doxorubicin/cyclophosphamide and GV therapy
Measured: 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
gpNMB expression by immunohistochemistry prior to and following doxorubicin/cyclophosphamide and GV therapy
Measured: Prior to therapy (in the 28 days prior to starting study treatment) and 3-6 weeks after last GV infusion for each patient

Timeline

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

1 May 20181 May 2018

First posted22 Mar 2018
Study start1 May 2018
Primary completion1 May 2018 (estimated)
Study completion1 May 2018

Why it stopped: Pharmaceutical company decided to withdraw funding and not provide drug.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
More trials run by University of VirginiaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03473691
Sponsor's protocol ID: TBDBreast50
Acronym: Breast50
Status last verified: Dec 2024
First submitted: 14 Feb 2018
Last updated: 9 Dec 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03473691
Acronym / sponsor ID: Breast50 / TBDBreast50
Conditions: Triple Negative Breast Cancer
Phase: Early Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Pharmaceutical company decided to withdraw funding and not provide drug.
Enrolment: 0 participants (actual)
Lead sponsor: University of VirginiaUniversity, hospital or other
Collaborators: Celldex Therapeutics
Study start: 1 May 2018 (actual)
Primary completion: 1 May 2018 (estimated)
Study completion: 1 May 2018 (actual)
First posted: 22 Mar 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Glembatumumab vedotin (GV)	Experimental	Drug: Glembatumumab Vedotin

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (20 listed)

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.

Key exclusion criteria (15 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Glembatumumab VedotinAlso: CDX-011Standard 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.	Drug	Glembatumumab vedotin (GV)

Primary outcome

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
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.
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.

3 secondary outcomes

Efficacy
Time frame: 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.
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

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Patrick Dillon, MD principal investigator

University of Virginia

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Glembatumumab Vedotin in people with Triple Negative Breast Cancer, run by University of Virginia.

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 20 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 9 Dec 2024. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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?

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)). The study lists 3 primary outcomes in all. 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 NCT03473691.

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 9 Dec 2024.