Metastatic Salivary Gland Carcinoma, Recurrent Salivary Gland Carcinoma, Stage IV Major Salivary Gland Cancer AJCC v8, Adenoid Cystic Carcinoma
Conditions
Brief summary
This phase II trial studies the effect of pemetrexed and pembrolizumab in treating patients with salivary gland cancer that has come back (recurrent) and/or has spread to other places in the body (metastatic). Chemotherapy drugs, such as pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to evaluate whether pembrolizumab, an immunotherapy drug, in combination with the chemotherapy drug, pemetrexed, has an effect on advanced salivary gland cancer.
Detailed description
PRIMARY OBJECTIVE: I. To determine the clinical benefit rate (CBR) of the combination of pembrolizumab and pemetrexed in patients with recurrent or metastatic adenoid cystic salivary gland cancer. (Group A1, adenoid cystic carcinoma \[ACC\]) II. To determine the response rate of the combination of pembrolizumab and pemetrexed in patients with recurrent or metastatic salivary gland cancer (recurrent/metastatic salivary gland cancer \[R/M SGC\]). (Groups A and B, ACC and non-ACC) SECONDARY OBJECTIVES: I. To determine the progression-free survival (PFS), overall survival (OS), response rate (ACC cohort), CBR rate (non-ACC), and adverse events of the combination of pembrolizumab and pemetrexed in patients with recurrent or metastatic salivary gland cancer (R/M SGC). II. To assess safety and tolerability of the combination of pembrolizumab and pemetrexed in patients with recurrent or metastatic salivary gland cancer (R/M SGC). CORRELATIVE RESEARCH OBJECTIVES: I. To investigate the frequency of MTAP loss by immunohistochemistry in R/M SGC and whether it correlates with enhanced response to pemetrexed. II. To measure the degree of PDL1 expression using formalin-fixed tumor samples, and determine the extent of PDL1 expression correlates with response to study treatment. III. To investigate expression of thymidylate synthase by immunohistochemistry in R/M SGC and whether it correlates with enhanced response to pemetrexed. IV. To investigate circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and correlation with response to study treatment. V. To prospectively investigate circulating prostate-specific membrane antigen (PSMA) extracellular vesibles (EVs) and correlate with disease burden and treatment response for patients with adenoid cystic carcinoma in Cohort A1. VI. To prospectively investigate PSMA positron emission tomography (PET)/computed tomography (CT) as an imaging modality for patients with adenoid cystic carcinoma in Cohort A1. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Cycles of pemetrexed disodium repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who had stable disease, partial response, or complete response after completion of 35 cycles of pembrolizumab, may continue pembrolizumab for an additional 17 cycles (1 year) in the absence of disease progression or unacceptable toxicity. Patients additionally undergo blood sample collection, CT, PET/CT or magnetic resonance imaging (MRI) and may also undergo PSMA PET on study. After completion of study intervention, patients are followed up at 30 days, and then every 3 months for up to 3 years.
Interventions
BIOLOGICALPembrolizumab
Given IV
DRUGPemetrexed Disodium
Given IV
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREComputed Tomography
Undergo CT or PET/CT
PROCEDUREPositron Emission Tomography
Undergo PET
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
PROCEDUREPSMA PET Scan
Undergo PSMA PET
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* REGISTRATION - INCLUSION CRITERIA * Age \>= 18 years * Histologically confirmed diagnosis of recurrent or metastatic salivary gland cancer not amenable to curative-intent therapy * COHORT A1: Rochester Minnesota only: Diagnosis of adenoid cystic carcinoma (ACC) * Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria * NOTE: Tumor lesions in a previously irradiated area are considered measurable disease if progression has been demonstrated in such lesions. Disease that is measurable by physical examination only is not eligible * Prior treatment: * Prior treatment with checkpoint inhibitor(s) allowed * Any number of lines of prior therapy in the recurrent/metastatic setting is permitted at the investigator's discretion * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * NOTE: PS must be assessed again within 7 days prior to first dose of study drug * Hemoglobin \>= 9.0 g/dL (obtained =\< 8 days prior to registration) * NOTE: Must be met without growth factor support and no transfusions \<14 days prior to testing * Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 8 days prior to registration) * Platelet count \>= 100,000/mm\^3 (obtained =\< 8 days prior to registration) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 8 days prior to registration) * Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement) (obtained =\< 8 days prior to registration) * Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained =\< 8 days prior to registration) * Creatinine =\< 1.5 x ULN OR calculated creatinine clearance \>= 45 ml/min using the Cockcroft-Gault formula (obtained =\< 8 days prior to registration) * Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only * Note: If testing done for eligibility is \> 72 hours prior to first dose, then pregnancy testing must be repeated and result must be negative for patient to receive treatment * Persons able to become pregnant OR able to father a child must be willing to use an adequate method of contraception while on treatment and for 180 days after last treatment * Life expectancy \>= 12 weeks * Provide written informed consent * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Willingness to provide mandatory blood specimens for correlative research * Willingness to provide mandatory tissue specimens for correlative research
Exclusion criteria
* REGISTRATION -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed response rate | Up to 24 weeks | Evaluated by Response Evaluation Criteria in Solid Tumors version 1.1. |
| Clinical benefit rate (CBR) | Up to 24 weeks | CBR will be defined as the rate of patients with stable disease, partial response or complete response as their best response during treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From study entry to death from any cause, assessed up to 3 years | Estimated using the Kaplan-Meier method. |
| Progression-free survival | From study entry to the first of either disease progression or death from any cause, assessed up to 3 years | Estimated using the Kaplan-Meier method. |
| Incidence of adverse events | Up to 3 years | The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5.0. The frequency and percentage of grade 3+ adverse events will be estimated. |
| Response rate [adenoid cystic carcinoma (ACC) cohort] | Up to 3 years | Response rate will be assessed using RECIST 1.1 criteria. The data will be reported descriptively, with frequencies and percentages. |
| CBR (non-ACC cohort) | Up to 3 years | CBR will be reported descriptively, with frequencies and percentages. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKatherine A. Price, MD
Mayo Clinic in Rochester
PRINCIPAL_INVESTIGATORAshish Chintakuntlawar, MBBS, PhD
Mayo Clinic
Outcome results
None listed