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.
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.
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.
