Testing the Use of Ado-Trastuzumab Emtansine Compared to the Usual Treatment (Chemotherapy With Docetaxel Plus Trastuzumab) or Trastuzumab Deruxtecan for Recurrent, Metastatic, or Unresectable HER2-Expressing Salivary Gland Cancers
A Phase II Trial of HER2-Targeted Therapies for Recurrent, Metastatic, or Unresectable HER2-Expressing Salivary Gland Cancers
3 other identifiers
interventional
146
1 country
150
Brief Summary
This phase II trial compares the effect of usual treatment of docetaxel chemotherapy plus trastuzumab, to ado-emtansine (T-DM1) in patients with HER2-postive salivary gland cancer that has come back (recurrent), that has spread from where it first started (primary site) to other places in the body, or cannot be removed by surgery (unresectable). This trial is also testing how well trastuzumab deruxtecan works in treating patients with HER2-low recurrent or metastatic salivary gland cancer. Trastuzumab is a form of targeted therapy because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by body's immune system. Trastuzumab emtansine contains trastuzumab, linked to a chemotherapy drug called emtansine. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers emtansine to kill them. Trastuzumab deruxtecan is a monoclonal antibody called traztuzumab, linked to a chemotherapy drug called deruxtecan. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors and delivers deruxtecan to kill them. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Trastuzumab emtansine may work better compared to usual treatment of chemotherapy with docetaxel and trastuzumab or trastuzumab deruxtecan in treating patients with recurrent, metastatic or unresectable salivary gland cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2023
Longer than P75 for phase_2
150 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 2, 2022
CompletedFirst Posted
Study publicly available on registry
June 7, 2022
CompletedStudy Start
First participant enrolled
March 3, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2028
May 4, 2026
April 1, 2026
5.4 years
June 2, 2022
April 28, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Progression free survival (PFS) (HER2-Positive Cohort)
Kaplan-Meier method will be used to estimate PFS rates. A log-rank test will be used to assess whether trastuzumab emtansine (T-DM1) shows a signal of better PFS than the control arm. Cox proportional hazards models, including the stratification factors and with/out other key covariates (e.g., Zubrod performance status), will be used to estimate the treatment effect hazard ratio along with 80% and 95% confidence intervals.
From randomization to disease progression or death due to any cause, whichever occurs first, assessed up to 5 years
Objective response rate (ORR) (HER2-Low Expressing Cohort)
Overall tumor response in patients will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Defined as the proportion of subjects who achieved the best overall response (BOR) of complete response (CR) or partial response (PR). NOTE: For an individual patient, BOR is the best response (in the order of CR, PR, stable disease \[SD\], and progressive disease \[PD\]). Summary statistics of the ORR posterior distribution and 95% credible intervals will also be provided.
From the start of treatment up to a year or until the progression of disease, unacceptable toxicity, physician discretion to discontinue treatment, or patient withdrawal of consent, whichever occurs first.), assessed up to 5 yeats
Secondary Outcomes (9)
ORR (HER2-Positive Cohort)
Up to 5 years
Duration of response (DOR) (HER2-Positive Cohort)
From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Overall survival (OS) (HER2-Positive Cohort)
Up to 5 years
Incidence of adverse events (HER2-Positive Cohort)
Up to 30 days from last study treatment dose
Treatment discontinuations due to AEs (HER2-Positive Cohort)
Up to 5 years
- +4 more secondary outcomes
Other Outcomes (1)
Objective Response Rate (ORR) for patients who receive crossover treatment to T-DM1/TH following disease progression on the TH/T-DM1 arm
Up to 5 years
Study Arms (3)
Arm I (docetaxel, trastuzumab)
ACTIVE COMPARATORPatients receive docetaxel IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive trastuzumab IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients on Arm I (TH) can cross over to Arm II (T-DM1) after first progression. Patients undergo a CT scan or MRI throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening.
Arm II (trastuzumab emtansine)
EXPERIMENTALPatients receive trastuzumab emtansine IV over 90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients on Arm II (T-DM1) can cross over to Arm I (TH) after first progression. Patients undergo a CT scan or MRI throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening.
Arm III (trastuzumab deruxtecan)
EXPERIMENTALPatients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan or MRI and ECHO or MUGA scan throughout the trial. Patients may also undergo blood sample collection and during screening and on study, as well as a biopsy during screening.
Interventions
Undergo a biopsy
Undergo blood sample collection
Ancillary studies
Given IV
Given IV
Given IV
Undergo MUGA
Undergo MRI
Undergo a CT scan
Undergo ECHO
Given IV
Eligibility Criteria
You may qualify if:
- Pathologically (histologically or cytologically) proven diagnosis of HER2-positive OR HER2-low expressing recurrent/metastatic salivary gland cancer (SGC)
- HER2-positive cohort:
- Note: The majority of HER2-positive SGCs are salivary duct carcinoma (SDCs), but to a lesser extent, other SGC subtypes can be HER2-positive (e.g., adenocarcinomas, mucoepidermoid carcinomas, etc.) and are eligible to be included on the study. Additionally, pathologists may sign out SDCs under other descriptors (e.g., ex-pleomorphic adenoma, adenocarcinoma), and these would be eligible if they are HER2-positive.
- Note: HER2 evaluation based on local site immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH), or local/commercial next-generation sequencing (NGS) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-positive":
- Immunohistochemistry (IHC) (3+) per the College of American Pathologists (CAP) breast cancer guidelines
- Gene amplification by FISH (HER2/CEP17 ratio \>= 2.0)
- Gene amplification by NGS (fold change \>= 2)
- HER2-low expressing cohort:
- Note: Local HER2 evaluation by immunohistochemistry (IHC) or fluorescent in-situ hybridization (FISH) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-low":
- IHC 1+ per the College of American Pathologists (CAP) breast cancer guidelines
- IHC 2+ without evidence of amplification by FISH
- Patients with unresectable disease who are not candidates for curative surgery or radiation OR recurrent OR metastatic disease that is evident on radiologic imaging
- Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
- HER2-positive cohort: Measurable or non-measurable disease by the RECIST v1.1 criteria. HER2-low expressing cohort: Measurable disease by the RECIST v1.1 criteria
- +29 more criteria
You may not qualify if:
- HER2-positive cohort: Prior systemic therapy for the study cancer in the unresectable or recurrent and/or metastatic disease setting
- Note: Prior chemotherapy for a different cancer is allowed; prior androgen receptor targeted therapy in any setting is allowed; prior systemic therapy, including HER2-directed therapies given as neoadjuvant therapy, adjuvant therapy, and/or concurrently with radiation is allowed
- HER2-low expressing cohort: HER2 directed therapy for unresectable or recurrent or metastatic disease is not allowed
- Severe, active co-morbidity defined as follows:
- Unstable angina requiring hospitalization in the last 6 months
- Myocardial infarction within the last 6 months
- New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
- Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing
- Patient must not have an active infection requiring IV antibiotics, antivirals, or antifungals
- HER2-positive cohort only: \>= grade 3 peripheral neuropathy
- Interstitial lung disease or pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on chest CT scan
- Any hemorrhage or bleeding event grade \>= 3 within 28 days prior to registration
- History of allergic reactions to compounds of similar chemical or biologic composition to: HER2-positive cohort: ado-trastuzumab emtansine, trastuzumab, and/or docetaxel (or any of their excipients). HER2-low expressing cohort: DS-8201a (trastuzumab deruxtecan), trastuzumab
- History of exposure to the following cumulative doses of anthracyclines:
- Doxorubicin or liposomal doxorubicin \> 500 mg/m\^2
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologylead
- National Cancer Institute (NCI)collaborator
Study Sites (150)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Kaiser Permanente Dublin
Dublin, California, 94568, United States
Kaiser Permanente-Fremont
Fremont, California, 94538, United States
Kaiser Permanente Fresno Orchard Plaza
Fresno, California, 93720, United States
Kaiser Permanente-Fresno
Fresno, California, 93720, United States
City of Hope at Irvine Lennar
Irvine, California, 92618, United States
Kaiser Permanente- Modesto MOB II
Modesto, California, 95356, United States
Kaiser Permanente-Modesto
Modesto, California, 95356, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, 94304, United States
Kaiser Permanente-Roseville
Roseville, California, 95661, United States
Kaiser Permanente Downtown Commons
Sacramento, California, 95814, United States
Kaiser Permanente-South Sacramento
Sacramento, California, 95823, United States
Kaiser Permanente-San Francisco
San Francisco, California, 94115, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, 95119, United States
Kaiser Permanente San Leandro
San Leandro, California, 94577, United States
Kaiser San Rafael-Gallinas
San Rafael, California, 94903, United States
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051, United States
Kaiser Permanente-Santa Rosa
Santa Rosa, California, 95403, United States
Kaiser Permanente-South San Francisco
South San Francisco, California, 94080, United States
Kaiser Permanente-Vallejo
Vallejo, California, 94589, United States
Kaiser Permanente-Walnut Creek
Walnut Creek, California, 94596, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UCHealth Highlands Ranch Hospital
Highlands Ranch, Colorado, 80129, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619, United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642, United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687, United States
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
McFarland Clinic - Ames
Ames, Iowa, 50010, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
Saint Anthony Regional Hospital
Carroll, Iowa, 51401, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
Broadlawns Medical Center
Des Moines, Iowa, 50314, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
UI Healthcare Mission Cancer and Blood - Fort Dodge
Fort Dodge, Iowa, 50501, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263, United States
The Iowa Clinic PC
West Des Moines, Iowa, 50266, United States
HaysMed
Hays, Kansas, 67601, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
Lawrence Memorial Hospital
Lawrence, Kansas, 66044, United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
Salina Regional Health Center
Salina, Kansas, 67401, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
UPMC Western Maryland
Cumberland, Maryland, 21502, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University Health Truman Medical Center
Kansas City, Missouri, 64108, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
East White Plains, New York, 10604, United States
Mount Sinai Chelsea
New York, New York, 10011, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Trinity's Tony Teramana Cancer Center
Steubenville, Ohio, 43952, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
Cancer Centers of Southwest Oklahoma Research
Lawton, Oklahoma, 73505, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
UPMC Altoona
Altoona, Pennsylvania, 16601, United States
UPMC-Heritage Valley Health System Beaver
Beaver, Pennsylvania, 15009, United States
UPMC Hillman Cancer Center at Butler Health System
Butler, Pennsylvania, 16001, United States
UPMC Camp Hill
Camp Hill, Pennsylvania, 17011, United States
Carlisle Regional Cancer Center
Carlisle, Pennsylvania, 17015, United States
UPMC Hillman Cancer Center - Passavant - Cranberry
Cranberry Township, Pennsylvania, 16066, United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505, United States
UPMC Cancer Center at UPMC Horizon
Farrell, Pennsylvania, 16121, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601, United States
UPMC Pinnacle Cancer Center/Community Osteopathic Campus
Harrisburg, Pennsylvania, 17109, United States
IRMC Cancer Center
Indiana, Pennsylvania, 15701, United States
UPMC-Johnstown/John P. Murtha Regional Cancer Center
Johnstown, Pennsylvania, 15901, United States
UPMC Cancer Center at UPMC McKeesport
McKeesport, Pennsylvania, 15132, United States
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
Mechanicsburg, Pennsylvania, 17050, United States
UPMC Hillman Cancer Center - Monroeville
Monroeville, Pennsylvania, 15146, United States
UPMC Hillman Cancer Center in Coraopolis
Moon Township, Pennsylvania, 15108, United States
UPMC Hillman Cancer Center - Part of Frick Hospital
Mount Pleasant, Pennsylvania, 15666, United States
UPMC Cancer Center-Natrona Heights
Natrona Heights, Pennsylvania, 15065, United States
UPMC Hillman Cancer Center - New Castle
New Castle, Pennsylvania, 16105, United States
Arnold Palmer Cancer Center Medical Oncology Norwin
North Huntingdon, Pennsylvania, 15642, United States
UPMC-Saint Margaret
Pittsburgh, Pennsylvania, 15215, United States
UPMC-Mercy Hospital
Pittsburgh, Pennsylvania, 15219, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
UPMC-Passavant Hospital
Pittsburgh, Pennsylvania, 15237, United States
UPMC-Saint Clair Hospital Cancer Center
Pittsburgh, Pennsylvania, 15243, United States
UPMC Cancer Center at UPMC Northwest
Seneca, Pennsylvania, 16346, United States
UPMC Cancer Center-Uniontown
Uniontown, Pennsylvania, 15401, United States
UPMC Cancer Center-Washington
Washington, Pennsylvania, 15301, United States
Divine Providence Hospital
Williamsport, Pennsylvania, 17754, United States
UPMC Memorial
York, Pennsylvania, 17408, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Dartmouth Cancer Center - North
Saint Johnsbury, Vermont, 05819, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548, United States
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, 53149, United States
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, 53188, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alan L Ho
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 2, 2022
First Posted
June 7, 2022
Study Start
March 3, 2023
Primary Completion (Estimated)
July 31, 2028
Study Completion (Estimated)
July 31, 2028
Last Updated
May 4, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.