Pembrolizumab and Docetaxel in Treating Participants with Poorly Chemo-Responsive and Unresectable Thyroid and Salivary Gland Cancers
- Patients must have histologically confirmed disease that is unresectable and not amenable to curative intent therapy: * Cohort A: salivary gland cancers (mucoepidermoid carcinoma, adenocarcinoma, adenoidcystic carcinoma, acinic cell carcinoma, or other histology) originating in salivary glands * Cohort B: thyroid cancer, radioactive iodine (RAI)-refractory and after failure, intolerance to or refusal of anti-antiangiogenic therapy, or with evidence of dedifferentiated or anaplastic histology
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Consent to undergo on treatment biopsy if tumor is accessible and safe to biopsy
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, bone only metastatic disease may be allowed on approval from study principal investigator (PI)
- Life expectancy of greater than 12 weeks
- Available tissue for PD-L1 staining (archival or new core needle biopsy at baseline if no archival tissue available); a minimum of 10 slides are required (unless approval from the PI is obtained)
- Absolute neutrophil count (ANC) >= 1,500/mcL, should be performed within 10 days of treatment initiation
- Platelets >= 100,000/mcL, should be performed within 10 days of treatment initiation
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment), should be performed within 10 days of treatment initiation
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearnace [CrCl]) >= 40 mL/min for subject with creatinine levels > 2.0 X institutional ULN, should be performed within 10 days of treatment initiation
- Serum total bilirubin =< 1.2 X ULN OR in case of Gilbert’s disease an elevated total bilirubin is allowed if direct bilirubin is =< 40% of total, should be performed within 10 days of treatment initiation
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 2.5 X ULN, should be performed within 10 days of treatment initiation
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants, should be performed within 10 days of treatment initiation
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, should be performed within 10 days of treatment initiation
- Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours of receiving first dose of study treatment; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy; abstinence is considered an acceptable method of contraception
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy in excess of prednisone 10 mg/24 h equivalent, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has a known history of active TB (Bacillus tuberculosis)
- Has hypersensitivity to pembrolizumab, docetaxel or any of its excipients
- Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study day 1, or targeted small molecule therapy within 2 weeks prior to study day 1, or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier, with the exception of lymphopenia or asymptomatic aberrancies of sodium, amylase, lipase or alkaline phosphatase
- Has not recovered from prior surgery, chemotherapy or radiation therapy from adverse events due to a previous treatment/administered agent (i.e., =< grade 1 or return to baseline prior to treatment) * Note: subjects with =< grade 2 neuropathy, any grade hearing loss or tinnitus, or typical side effects from radiotherapy are an exception to this criterion and may qualify for the study * Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- 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 or other cancers that are not likely to influence life expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy)
- Has known active (growing) central nervous system (CNS) metastases and/or carcinomatous meningitis; prior radiation or resection is acceptable if clinically stable for at least 4 weeks
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids in excess of prednisone 10 mg/24 h equivalent or immunosuppressive drugs) and would represent significant morbidity risk in judgement of investigator; replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has known history of, or any evidence of, active non-infectious pneumonitis
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has a known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies); patients with treated HIV, as evidenced by stable CD4 > 200 for at least 6 months, are eligible
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Has received a live vaccine within 30 days of planned start of study therapy
- History of organ transplant that requires use of immunosuppressives
- Any condition that would jeopardize the safety of the subject or compliance with the protocol
- Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of study drug administration, New York Heart Association class III or IV congestive heart failure, and arrhythmia requiring therapy * Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed within 30 days prior to initiation of treatment
I. Response rate.
I. Overall and progression free survival.
I. Induction of PD-L1 expression, induction of tumor inflammation and tumor infiltration by cluster of differentiation 3 (CD3+) lymphocytes in T cell excluded versus (vs) permissive tumors and in PD-L1 positive vs negative tumors.
II. Induction of Interferon-gamma gene expression profile (GEP) (and evaluation of response rate [RR], progression free survival [PFS], and overall survival [OS] in GEP positive and GEP negative patients) in T cell excluded vs permissive tumors and in PD-L1 positive vs negative tumors.
III. Determine micro-environmental changes induced by anti-PD-1 + chemotherapy comparing pre-treatment and on treatment samples, namely evaluating different immune cell compartments (e.g. elimination of myeloid-derived suppressor cells [MDSCs], and M2 macrophages).
IV. Assess underlying mutational burden and correlation with outcome.
V. Assess serum cytokine flux during combined taxane and PD-1 blockade.
VI. Assess transcriptional changes in immune cell subsets in blood during treatment (eg… CD38+ or Ki67+ on circulating CD8 and CD4 subsets).
VII. Stool samples will be collected and analyzed for changes between baseline and on-treatment sample
VIII. Select cases with sufficient tissue.
Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and docetaxel IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 35 courses of pembrolizumab and for up to 6 courses of docetaxel in the absence of disease progression or unacceptable toxicity. Participants who attained confirmed complete response, are treated for at least 24 months with pembrolizumab, and then experience radiographic disease progression, may receive pembrolizumab and docetaxel for 1 year at the discretion of the investigator.
After completion of study treatment, participants are followed up at 30 days, every 8-12 weeks for 1 year, and then every 12-16 weeks for up to 2 years.
Trial Phase Phase II
Trial Type Treatment
University of Chicago Comprehensive Cancer Center
Tanguy Y. Seiwert
- Primary ID IRB17-0994
- Secondary IDs NCI-2018-00339
- Clinicaltrials.gov ID NCT03360890