Metastatic NUT Carcinoma, Unresectable NUT Carcinoma
Conditions
Brief summary
This phase II trial studies how well cemiplimab works in treating patients with nuclear protein of testis (NUT) carcinoma for which no treatment is currently available (incurable) and that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVE: I. Assess the preliminary effect of cemiplimab treatment on survival in patients with recurrent, or advanced NUT carcinoma (NC) at 6 months from start of treatment. SECONDARY OBJECTIVES: I. Assess NC patients treated with cemiplimab for overall radiographic response. II. Assess the duration of documented radiographic response in cemiplimab treated NC patients. III. Assess the clinical benefit by radiographic response rate in cemiplimab treated NC patients. IV. Assess the overall survival (OS) of cemiplimab-treated NC patients. V. Assess the safety, toxicity, and tolerability of cemiplimab treatment in patients with NC. VI. Assess quality of life (QOL) for cemiplimab treated NC patients via the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version \[v\]3.0 survey. EXPLORATORY OBJECTIVES: I. To comprehensively molecularly characterize NC samples obtained from patients. II. To gain deeper insights into the spatial organization of NUT midline carcinoma (NMC). III. Characterize the landscape of immune cells in treatment-naïve and previously treated NC patients. OUTLINE: Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 32 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or digital photography as well as blood sample collection and optional tumor biopsies throughout the study. After completion of study treatment, patients are followed every 3 months for 24 months.
Interventions
PROCEDUREBiopsy Procedure
Undergo optional biopsy
PROCEDUREBiospecimen Collection
Undergo collection of blood samples
BIOLOGICALCemiplimab
Given IV
PROCEDUREComputed Tomography
Undergo CT
OTHERDigital Photography
Undergo digital photography
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Northwestern University
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
* Patients must have a histologically confirmed NUT carcinoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. * Patient may be treatment naïve or have had prior surgery, radiation, or any systemic therapy (with the exceptions noted in the
Exclusion criteria
). * Patients must have histologically or cytologically confirmed NUT carcinoma based on the ectopic expression of NUT protein per World Health Organization (WHO) criteria as determined by immunohistochemistry (IHC) and/or detection of NUT gene translocation as determined by fluorescence in situ hybridization (FISH) at a Clinical Laboratory Improvement Act (CLIA) certified laboratory and/or by detection of the NUT gene translocation as determined by sequencing (e.g., deoxyribonucleic acid \[DNA\] next generation sequencing \[NGS\] or ribonucleic acid \[RNA\] sequencing) at a CLIA certified laboratory. * Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. * Patients must be age ≥ 18 years. * Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Leukocytes (WBC) ≥ 3,000/mcL. * Absolute neutrophil count (ANC) ≥ 1,500/mcL. * Hemoglobin (Hgb) ≥ 9 g/dL. * Platelets (PLT) ≥ 100,000/mcL. * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3 x institutional ULN. * Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional ULN. * Creatinine ≤ 1.5 x institutional ULN. * Glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m\^2. * Estimated (e)GFR is estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. * 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. * The effects of cemiplimab on the developing human fetus are unknown. For this reason and because immune checkpoint inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, patients of child-bearing potential (POCBP) and their partners with sperm-producing reproductive capacity must agree to use adequate contraception from time of informed consent, for the duration of study participation, and for 6 months following completion of cemiplimab therapy. Should a POCBP become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. * NOTE: A POCBP is any patient (regardless of gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) with an egg-producing reproductive tract who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months) * POCBP must have a negative pregnancy test prior to registration on study. * Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must also agree to use adequate contraception with partners of childbearing potential from time of informed consent, for the duration of study participation, and for 6 months after completion of administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | At the beginning of cycle 1, day 1 (each cycle is 21 days) to the time of death from any cause, assessed at 6 months. | The statistical analysis plan for the percentage of patients alive at 6 months will primarily involve a survival analysis using Kaplan-Meier methods. The point estimate of the treatment effect, as well as the associated 2-sided 95% confidence interval (CI), will be estimated using a Cox-proportional-hazards model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) | From the day of first documented response to trial therapy (CR or PR, whichever is first recorded) and subsequent disease progression, assessed up to 24 months after completion of study treatment | Response is defined as confirmed CR or confirmed PR per RECIST 1.1; and disease progression is defined as progressive disease per RECIST 1.1. Will be summarized using descriptive statistics, and the CR rate of nuclear protein of testis carcinoma in patients will be determined. |
| Clinical response rate | From the initiation of trial therapy until the patient experiences disease progression, initiates subsequent anti-cancer therapy, or completes study participation (whichever occurs first, assessed up to 24 months after completion of study treatment | Will calculate the proportion of treated, evaluable patients who experience clinical benefit from trial therapy. Clinical benefit is defined as confirmed CR; confirmed PR; or stable disease for ≥ 6 months per RECIST 1.1. Will be estimated with a proportion and CI. |
| Overall response rate (ORR) | Up to 24 months after completion of study treatment | Will calculate the proportion of treated patients who experience an objective response (confirmed complete response \[CR\] or confirmed partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1). The date of first response for either CR or PR will be used for the calculation of ORR. The proportion of evaluable patients experiencing an objective response will be estimated with a 95% exact binomial CI. The confidence interval will be adjusted for the sequential nature of the two-stage procedure. |
| Incidence of adverse events | Up to 24 months after completion of study treatment | Will collect and report the frequency of adverse events by type, severity (grade), timing, and attribution to cemiplimab, according to the National Cancer Institute Common Terminology Criteria for Adverse events version 5.0. Safety and tolerability will be summarized by providing a frequency of adverse events by severity, type, timing and attribution. |
| Quality of life (QOL) | Up to 24 months after completion of study treatment | Evaluate changes in quality of life per EORTC QLQ - THY34 questionnaire derived data which will be used to report QOL outcomes. |
| OS | From start of treatment (Cycle 1, Day 1) to the time of death from any cause, assessed at up to 24 months after completion of study treatment | Will be analyzed using the Kaplan-Meier method. The median OS estimate will be reported along with the CI. |
Countries
United States
Contacts
Primary ContactStudy Coordinator
Outcome results
None listed