Pemetrexed and Pembrolizumab for the Treatment of Recurrent and/or Metastatic Salivary Gland Cancer

  • STATUS
    Recruiting
  • End date
    Jun 3, 2026
  • participants needed
    45
  • sponsor
    Mayo Clinic
Updated on 20 April 2022

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.

Description

PRIMARY OBJECTIVE:

I. To determine the response rate of the combination of pembrolizumab and pemetrexed in patients with recurrent or metastatic salivary gland cancer (R/M SGC).

SECONDARY OBJECTIVES:

I. To determine the progression-free survival (PFS), overall survival (OS), 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.

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.

After completion of study intervention, patients are followed up at 30 days, and then every 3 months for up to 3 years.

Details
Condition Metastatic Salivary Gland Carcinoma, Recurrent Salivary Gland Carcinoma, Stage IV Major Salivary Gland Cancer AJCC v8, Stage IVA Major Salivary Gland Cancer AJCC v8, Stage IVB Major Salivary Gland Cancer AJCC v8, Stage IVC Major Salivary Gland Cancer AJCC v8
Treatment Pembrolizumab, pemetrexed disodium
Clinical Study IdentifierNCT04895735
SponsorMayo Clinic
Last Modified on20 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

REGISTRATION - INCLUSION CRITERIA
Age >= 18 years
Histologically confirmed diagnosis of recurrent or metastatic salivary gland cancer not amenable to curative-intent therapy
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
Platelet count >= 100,000/mm^3 (obtained =< 8 days prior to registration)
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
Life expectancy >= 12 weeks
Persons able to become pregnant OR able to father a child must be willing to use an
Provide written informed consent
adequate method of contraception while on treatment and for 180 days after
Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
last treatment
Willingness to provide mandatory blood specimens for correlative research
Willingness to provide mandatory tissue specimens for correlative research

Exclusion Criteria

REGISTRATION - EXCLUSION CRITERIA
Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
Pregnant persons
Nursing persons
Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception
Persons expecting to conceive or father children during study treatment or within 180 days (6 months) after the last treatment
Any of the following prior therapies
Received an investigational agent or used an investigational device or
Surgery < 3 weeks prior to registration
participated in a study of an investigational agent < 4 weeks prior to
Systemic anti-cancer therapy < 3weeks prior to registration
registration
Radiotherapy < 2 weeks prior to registration OR Palliative radiation < 1 week prior to registration
Known active human immunodeficiency virus (HIV) infection (defined as patients who are
NOTES: Must have recovered from all radiation related adverse effects (=< grade 1) Must not currently require corticosteroids Must not have had radiation pneumonitis
not on anti-retroviral treatment and have detectable viral load and CD4+ <
Live vaccine < 4 weeks prior to registration
ml)
NOTES: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
Active autoimmune disease requiring systemic treatment < 2 years prior to
registration, documented history of severe autoimmune disease, or a syndrome
NOTE: HIV-positive patients who are well controlled on anti-retroviral therapy are allowed to enroll
that requires systemic steroids or immunosuppressive agents with use of
disease modifying agents, corticosteroids or immunosuppressive drugs
NOTE: Exceptions are allowed for
Vitiligo
Resolved childhood asthma/atopy
Intermittent use of bronchodilators or inhaled steroids
Daily steroids at dose of =< 10 mg of prednisone (or equivalent)
Local steroid injections
Stable hypothyroidism on replacement therapy
Stable diabetes mellitus on therapy (with or without insulin)
Sjogren's syndrome
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
Current or prior use of immunosuppressive medication < 14 days prior to registration
NOTE: The following are exceptions to this criterion
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection)
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
Steroids as premedication for hypersensitivity reactions (e.g., premedication for computed tomography [CT] scans)
Uncontrolled intercurrent illness including, but not limited to
Ongoing or active infection requiring systemic therapy
Interstitial lung disease or clinically significant pleural effusion
Clinically significant ascites
Serious, chronic gastrointestinal conditions associated with diarrhea (e.g., Crohn's disease or others)
Known history of hepatitis B (i.e., known positive hepatitis B virus [HBV] surface antigen [HBsAg] reactive)
Known active hepatitis C (i.e., positive for hepatitis C virus [HCV] ribonucleic acid [RNA] detected by polymerase chain reaction [PCR])
Known active tuberculosis (TB)
Symptomatic congestive heart failure
Unstable angina pectoris
Unstable cardiac arrhythmia or
Psychiatric illness/social situations that would limit compliance with study requirements (e.g., substance abuse)
Co-morbid systemic illnesses or other severe concurrent disease or current evidence of
Failure to recover to =< grade 1 (or baseline) from adverse events due to previously administered therapies or prior surgery
any condition, therapy, or laboratory abnormality which, in the judgment of
Exceptions: Neuropathy, fatigue, and/or alopecia may be grade 1
the investigator, would make the patient inappropriate for entry into this
Known active central nervous system (CNS) metastases
study or interfere significantly with the proper assessment of safety and
NOTE: Patients with previously treated brain metastases may participate provided all of the following are true
toxicity of the prescribed regimens
They are stable (without evidence of progression by imaging =< 4 weeks prior to registration and any neurologic symptoms have returned to baseline)
Have no evidence of new or enlarging brain metastases, and
Are not using steroids =< 14 days prior to registration
Known leptomeningeal disease
Hypersensitivity (>= grade 3) to pembrolizumab or any of its excipients
Previous serious adverse event (>= grade 3) attributed to prior checkpoint inhibitor therapy
History of (non-infectious) pneumonitis that required steroids or has current pneumonitis
History of grade >= 3 immune-related adverse event or any grade of immune-related neurologic or ocular adverse event while receiving immunotherapy
Note: Patients who had endocrine adverse events =< grade 2 are allowed to enroll if they are stable on appropriate replacement therapy and asymptomatic
Other active malignancy < 2 years prior to registration
EXCEPTIONS: Non-melanotic skin cancer, superficial bladder cancer, papillary thyroid cancer, or carcinoma-in-situ of the cervix or others curatively treated and now considered to be at less than 30% risk of relapse
History of allogenic tissue/solid organ transplant
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