Post-op T-DM1 in HER-2+ Salivary Gland Carcinomas

NCT ID: NCT04620187

Last Updated: 2025-02-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-24

Study Completion Date

2027-02-01

Brief Summary

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This research is being done to see how safe and effective the use of the study drug Ado-trastuzumab (T) emtansine (DM1), T-DM1, and standard of care chemoradiation are when used together in treating HER2-positive salivary gland cancer. It will also examine the effectiveness of study drug Ado-trastuzumab (T) emtansine (DM1) on cancer recurrence.

Detailed Description

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This is a phase II, open-label, non-randomized, multi-institutional study investigating postoperative or adjuvant human epidermal growth factor receptor (HER2)-directed therapy with adjuvant ado-trastuzumab emtansine (T-DM1) in HER2-positive salivary gland carcinomas (SGC).

This research study is:

* Studying the use of T-DM1 in combination with radiation and chemotherapy; and the use of maintenance T-DM1 alone for up to a year after surgery
* Evaluating the effectiveness, safety, and toxicity of T-DM1

T-DM1 is a specialized antibody targeting HER-2 (a protein that is expressed in some breast and salivary gland cancers). The drug is a HER-2 antibody that is bound to a chemotherapy agent (DM1) and delivered intravenously. T-DM1 then binds cancer cells that express HER-2 and is taken up into the cell to allow DM1 to kill cancer cells in a more targeted way. This allows the use of a targeted treatment along with chemoradiation to treat HER-2 expressing salivary cancers.

The U.S. Food and Drug Administration (FDA) has not approved T-DM1 for HER2-positive salivary gland cancer but it has been approved for other uses (for breast cancers that express HER2 protein).

The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits.

This research study involves radiation, chemotherapy, and targeted therapy given after surgery for up to 1-year, and participants will be followed for 3 years.

It is expected that about 55 people will take part in this research study.

Genentech is supporting this research study by providing the research study drug, T-DM1.

Conditions

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Salivary Gland Cancer HER2 Gene Mutation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard of Care + T-DM1 in HER2-Positive Salivary Gland Cancer

Participants will undergo standard of care surgery followed by standard of care radiation and chemotherapy with the addition of T-DM1.

Study cycles are 21 days (3 weeks):

* Participants will be given the study treatment T-DM1 at a predetermined dose (3.6 mg/kg) intravenously once (1x) every 3 weeks for up to 52 weeks (or about 1 year).
* Participants will be given standard of care radiation and chemotherapy

* Radiation will be given on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, and Cycle 3 Day 1
* Chemotherapy (cisplatin 40 mg/m2 intravenously or carboplatin AUC 2 intravenously) will be given on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, and Cycle 3 Day 1

Participants will be followed for 3 years.

Group Type EXPERIMENTAL

Ado-trastuzumab (T) emtansine (T-DM1)

Intervention Type DRUG

Intravenous infusion ever 21 days (3weeks) for 1 year (52 weeks)

Standard of Care Radiotherapy

Intervention Type RADIATION

Radiotherapy to shrink or kill tumors

Standard of Care Chemotherapy

Intervention Type DRUG

Intravenous injection

Interventions

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Ado-trastuzumab (T) emtansine (T-DM1)

Intravenous infusion ever 21 days (3weeks) for 1 year (52 weeks)

Intervention Type DRUG

Standard of Care Radiotherapy

Radiotherapy to shrink or kill tumors

Intervention Type RADIATION

Standard of Care Chemotherapy

Intravenous injection

Intervention Type DRUG

Other Intervention Names

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Kadcyla Radiation Cisplatin carboplatin

Eligibility Criteria

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Inclusion Criteria

* Subject must have histologically or cytologically confirmed, resectable stage II (with positive margins), III, IVA, or IVB locoregionally advanced salivary gland carcinoma (including any histologic subtype), as defined by 2017 American Joint Committee on Cancer (AJCC), 8th edition.
* Willing to provide tissue from a diagnostic biopsy or at the time of cancer resection, and blood samples before, during, and after treatment.
* HER2 positive disease as defined by any of the following:

* Tumor HER2 expression staining intensity of 2 or 3+ by IHC (from either a preoperative biopsy or resection specimen at the time of oncologic surgery)
* HER2 amplification as determined by FISH (HER2/CEP 17 ratio greater than or equal to 2.0 or HER2 mean copy number greater than or equal to 4.0)
* HER2 or ERBB2 mutated on tumor genomic sequencing assay (see Section 9.1 for permitted HER2 mutations)
* Age 18 years or older
* ECOG performance status ≤ 1 (Karnofsky ≥ 60%, see Appendix A)
* Participant must have normal organ and marrow function as defined below within 14 days prior to study registration:

* leukocytes ≥ 3,000/mcL
* absolute neutrophil count ≥ 1,000/mcL
* hemoglobin ≥ 9.0 g/dL
* platelets ≥ 100,000/mcL
* total bilirubin ≤ 2.0 g/dL
* AST(SGOT)/ALT(SGPT) ≤ 2.5× institutional upper limit of normal
* creatinine within normal institutional limits OR
* creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
* Serum calcium (corrected for albumin value), magnesium, and potassium levels within normal limits per institutional standards.
* Assessment of cardiac function either by an echocardiogram or a multi-gated acquisition (MUGA) scan prior to the therapy initiation, with a baseline left systolic ventricular ejection fraction (LVEF) ≥ 50% within 1 month prior to study registration.
* Ability to understand and the willingness to sign a written informed consent document.
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of T-DM1. "Women of childbearing potential (WOCBP)" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
* Men who are sexually active with WOCBP must agree to use any contraceptive method with a failure rate of less than 1% per year. Men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 6 months after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. See Appendix B for further guidance on contraception.

Exclusion Criteria

* Patient with AJCC 2017 8th edition stage I or stage IVC (metastatic) disease, or unresectable disease.
* Subject who has had prior radiation and/or chemotherapy for head and neck cancer.
* Any history of prior HER2 directed therapy.
* Active or uncontrolled infection.
* Pregnant or lactating women.
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Has a known additional malignancy that is progressing or requires active treatment.

Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and low risk prostate adenocarcinoma being managed with active surveillance. A history of another separate malignancy in remission without evidence of active disease in the last 2 years is permitted.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Glenn J. Hanna

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Glenn J Hanna, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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University of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status RECRUITING

University of Washington Medical Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Glenn J Hanna, MD

Role: CONTACT

617-632-3090

Facility Contacts

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Alexander T Pearson, MD, PhD

Role: primary

855-702-8222

Cancer Clinical Trials Office

Role: backup

855-702-8222

Glenn J Hanna, MD

Role: primary

617-632-3090

Glenn J. Hanna, MD

Role: primary

617-632-3090

Alan L Ho, MD, PhD

Role: primary

833-637-1274

Alan L Ho, MD, PhD

Role: primary

844-665-7394

Alan L Ho, MD, PhD

Role: primary

551-751-1007

Alan L Ho, MD, PhD

Role: primary

833-637-1274

Alan L Ho, MD, PhD

Role: primary

914-893-4461

Alan L Ho, MD, PhD

Role: primary

833-637-1274

Alan L Ho, MD, PhD

Role: primary

646-733-4430

Alan L Ho, MD, PhD

Role: primary

516-564-2022

Jay Liao, MD

Role: primary

Other Identifiers

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20-432

Identifier Type: -

Identifier Source: org_study_id

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