Testing the Use of Ado-Trastuzumab Emtansine Compared to the Usual Treatment (Chemotherapy With Docetaxel Plus Trastuzumab) for Recurrent, Metastatic, or Unresectable HER2-Positive Salivary Gland Cancer
Metastatic Salivary Gland Carcinoma, Recurrent Salivary Gland Carcinoma, Stage III Major Salivary Gland Cancer AJCC v8
About this trial
This is an interventional treatment trial for Metastatic Salivary Gland Carcinoma
Eligibility Criteria
Inclusion Criteria:
Pathologically (histologically or cytologically) proven diagnosis of HER2-positive salivary gland cancer (SGC)
- 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)
- 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
- Measurable or non-measurable disease by the RECIST v1.1 criteria
- History/physical examination within 30 days prior to registration
The following imaging within 60 days prior to registration:
- Computed tomography (CT) or magnetic resonance imaging (MRI) of the neck (diagnostic quality with contrast, unless contraindicated) AND
- CT scan of the chest (diagnostic quality with contrast, unless contraindicated) AND
- CT or MRI of the abdomen and pelvis, if clinically indicated (diagnostic quality with contrast, unless contraindicated)
- Age >= 18
- Left ventricular ejection fraction (LVEF) >= 50% assessed by echocardiogram or multigated acquisition (MUGA) scan within 30 days prior to registration
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 14 days prior to registration)
- Platelets >= 100,000 cells/mm^3 (within 14 days prior to registration)
- Hemoglobin >= 9.0 g/dL (within 14 days prior to registration) (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dL is acceptable.)
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance (CrCl) >= 30 mL/min by the Cockcroft-Gault formula (within 14 days prior to registration)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x institutional ULN (within 14 days prior to registration)
- Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial. Testing is not required for entry into protocol
For patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g., patients immunized against hepatitis B)
For patients with a known history of hepatitis C virus (HCV) infection, they must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
- Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
- Willing to use highly effective contraceptives for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 7 months following last dose of study drug; this inclusion is necessary because the treatment in this study may be significantly teratogenic (See Section 9 for definition of highly effective contraception). Women must refrain from donating eggs during this same period
- Men with partners of childbearing potential must be willing to use a highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner, and to continue the use of contraception for the duration of study treatment and for at least 7 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the pregnancy. Men must refrain from donating sperm during this same period
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information
Exclusion Criteria:
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
- Patients who have had chemotherapy or palliative-intent radiotherapy must have all toxicities related to prior treatment recovered to =< grade 1 prior to registration
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
- >= 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 ado-trastuzumab emtansine, trastuzumab, and/or docetaxel (or any of their excipients)
History of exposure to the following cumulative doses of anthracyclines:
- Doxorubicin or liposomal doxorubicin > 500 mg/m^2
- Epirubicin > 900 mg/m^2
- Mitoxantrone > 120 mg/m^2
- Note: If another anthracycline, or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of doxorubicin 500 mg/m^2
- Pregnancy and individuals unwilling to discontinue nursing
Sites / Locations
- University of Alabama at Birmingham Cancer CenterRecruiting
- City of Hope Comprehensive Cancer CenterRecruiting
- City of Hope at Irvine LennarRecruiting
- Stanford Cancer Institute Palo AltoRecruiting
- UCHealth University of Colorado HospitalRecruiting
- UCHealth Highlands Ranch HospitalRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Saint Luke's Cancer Institute - FruitlandRecruiting
- Saint Luke's Cancer Institute - MeridianRecruiting
- Saint Luke's Cancer Institute - NampaRecruiting
- Saint Luke's Cancer Institute - Twin FallsRecruiting
- Carle at The RiverfrontRecruiting
- Carle Physician Group-EffinghamRecruiting
- Carle Physician Group-Mattoon/CharlestonRecruiting
- Carle Cancer CenterRecruiting
- McFarland Clinic - AmesRecruiting
- Mercy Medical Center - Des MoinesRecruiting
- UPMC Western MarylandRecruiting
- University of Michigan Comprehensive Cancer CenterRecruiting
- Wayne State University/Karmanos Cancer InstituteRecruiting
- Weisberg Cancer Treatment CenterRecruiting
- Sanford Joe Lueken Cancer CenterRecruiting
- Mercy HospitalRecruiting
- Fairview Southdale HospitalRecruiting
- Abbott-Northwestern HospitalRecruiting
- Mayo Clinic in RochesterRecruiting
- Park Nicollet Clinic - Saint Louis ParkRecruiting
- Regions HospitalRecruiting
- United HospitalRecruiting
- Siteman Cancer Center at West County HospitalRecruiting
- Washington University School of MedicineRecruiting
- Siteman Cancer Center-South CountyRecruiting
- Siteman Cancer Center at Christian HospitalRecruiting
- Siteman Cancer Center at Saint Peters HospitalRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Memorial Sloan Kettering Basking RidgeRecruiting
- Memorial Sloan Kettering MonmouthRecruiting
- Memorial Sloan Kettering BergenRecruiting
- Memorial Sloan Kettering CommackRecruiting
- Memorial Sloan Kettering WestchesterRecruiting
- Mount Sinai ChelseaRecruiting
- Mount Sinai HospitalRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- Memorial Sloan Kettering NassauRecruiting
- Sanford Bismarck Medical CenterRecruiting
- Sanford Broadway Medical CenterRecruiting
- Sanford Roger Maris Cancer CenterRecruiting
- University of Cincinnati Cancer Center-UC Medical CenterRecruiting
- Ohio State University Comprehensive Cancer CenterRecruiting
- Trinity's Tony Teramana Cancer CenterRecruiting
- University of Cincinnati Cancer Center-West ChesterRecruiting
- Cancer Centers of Southwest Oklahoma ResearchRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- UPMC AltoonaRecruiting
- UPMC-Heritage Valley Health System BeaverRecruiting
- UPMC Hillman Cancer Center at Butler Health SystemRecruiting
- UPMC Camp HillRecruiting
- Carlisle Regional Cancer CenterRecruiting
- UPMC Hillman Cancer Center - Passavant - CranberryRecruiting
- UPMC Hillman Cancer Center ErieRecruiting
- UPMC Cancer Center at UPMC HorizonRecruiting
- UPMC Cancer Centers - Arnold Palmer PavilionRecruiting
- UPMC Pinnacle Cancer Center/Community Osteopathic CampusRecruiting
- IRMC Cancer CenterRecruiting
- UPMC-Johnstown/John P. Murtha Regional Cancer CenterRecruiting
- UPMC Cancer Center at UPMC McKeesportRecruiting
- UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer PavilionRecruiting
- UPMC Hillman Cancer Center - MonroevilleRecruiting
- UPMC Hillman Cancer Center in CoraopolisRecruiting
- UPMC Hillman Cancer Center - Part of Frick HospitalRecruiting
- Arnold Palmer Cancer Center Medical Oncology NorwinRecruiting
- UPMC Cancer Center-Natrona HeightsRecruiting
- UPMC Hillman Cancer Center - New CastleRecruiting
- UPMC-Saint MargaretRecruiting
- UPMC-Mercy HospitalRecruiting
- University of Pittsburgh Cancer Institute (UPCI)Recruiting
- UPMC-Passavant HospitalRecruiting
- UPMC-Saint Clair Hospital Cancer CenterRecruiting
- UPMC Cancer Center at UPMC NorthwestRecruiting
- UPMC Cancer Center-UniontownRecruiting
- UPMC Cancer Center-WashingtonRecruiting
- Divine Providence HospitalRecruiting
- UPMC MemorialRecruiting
- Medical University of South CarolinaRecruiting
- Sanford Cancer Center Oncology ClinicRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- Vanderbilt University/Ingram Cancer CenterRecruiting
- Norris Cotton Cancer Center-NorthRecruiting
- Medical College of WisconsinRecruiting
- ProHealth D N Greenwald CenterRecruiting
- ProHealth Oconomowoc Memorial HospitalRecruiting
- UW Cancer Center at ProHealth CareRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I (docetaxel, trastuzumab)
Arm II (trastuzumab emtansine)
Patients 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 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.