Malignant peripheral nerve sheath tumor (MPNST), not eligible for curative surgery
Conditions
Sponsors
Oslo University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male and female subjects of at least 18 years of age with metastatic or locally advanced/unresectable MPNST 1. Be willing and able to provide written informed consent/assent for the trial. 2. Be 18 years of age on day of signing informed consent. 3. Have measurable disease based on RECIST, version 1.1. 4. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. 5. Be willing to provide tissue from a newly obtained core or excisional biopsy of benign nevrofibromatosis lesion (NF1 patients only) 6. Have a performance status of 0 or 1 on the ECOG Performance Scale. 7. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation. 8. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 9. 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 (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. 10. 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. 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 4 weeks of the first dose of treatment. 2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 3. Has a known history of active TB (Bacillus Tuberculosis) 4. Hypersensitivity to pembrolizumab or any of its excipients. 5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 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. 6. Has had prior chemotherapy, targeted small molecule therapy, or radiation 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 a previously administered agent. - Note: Subjects with = Grade 2 neuropathy 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. 7. 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 cancer. 8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 10. Has known history of, or any evidence of active, non-infectious pneumonitis. 11. Has an active infection requiring systemic therapy. 12. 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. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 14. 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. 15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 17. Has kno
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main Objective: To evaluate the percentage of patients with curatively unresectable MPNST who have achieved clinical response; complete response (CR), partial response (PR), or stable disease (SD) at 18 weeks as assessed by the Investigator, by using iRECIST, v1.1. ;Secondary Objective: Secondary objectives: 1)Overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), and progression-free survival (PFS), assessed by the Investigator by using RECIST, v1.1. 2) To evaluate the percentage of patients who have achieved clinical response; CR, PR, or SD at 18 weeks , ORR, CBR, DOR, and PFS assessed by the Investigator by using immune-related response criteria, irRC. 3) To evaluate the percentage of patients who have achieved clinical response; CR, PR, or SD at 18 weeks, ORR, CBR, DOR, and PFS assessed by the Investigator by using Immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) 4) To evaluate overall survival (OS). 5) To evaluate the safety and tolerability of pembrolizumab in patients with MPNST. 6) To evaluate health-related quality of life changes from baseline in patients with MPNST, receiving pembrolizumab, using EORTC-QLQC30. In addition there are 7 Exploratory Objectives. ;Primary end point(s): Clinical response at 18 weeks: The percentage of patients with unresectable MPNST who have achieved clinical response; complete response (CR), partial response (PR), or stable disease (SD) at 18 weeks as assessed by using RECIST, v1.1.;Timepoint(s) of evaluation of this end point: The primary efficacy analysis will be percentage of patients with response, defined as CR, PR, or SD, and will be evaluated by the Investigator 18 weeks after start of treatment, according to RECIST, v1.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS): This is the gold standard endpoint to demonstrate efficacy of antineoplastic therapy. Progression free survival (PFS): This may be an acceptable scientific endpoint for clinical trials in oncology. RECIST 1.1 will be used to determine the dates of progression as this methodology is scientifically accepted. The first on-study radiographic imaging assessment will be performed at 9 weeks (±7 days) after first dose of study treatment and then every 6 weeks (±7 days) during treatment, and then every 8 weeks, or more frequently if clinically indicated. Patient Reported Outcomes: - Quality of life using EORTC QLQ-C30 - Safety will be assessed by reported adverse experiences using CTCAE, Version 4.0. - Planned Exploratory Biomarker Research ;Timepoint(s) of evaluation of this end point: Overall survival (OS) will be calculated from the date of randomization until death. Patients alive at 24 months after last enrolled patient will be treated as censored. OS will be estimated by the Kaplan Meier method. Progression free survival (PFS) will be measured as the time from first dose of pembrolizumab to the first progression recorded or death. If patients undergo curative surgical resection after start of treatment, PFS will be measured as time from first dose of pembrolizumab to disease recurrence after surgery or death. Patients who have not yet progressed or died 24 months after last enrolled patient will be treated as censored. PFS will be estimated by the Kaplan Meier method. | — |
Countries
Norway
Contacts
Public ContactProject Manager
Oslo University Hospital
Outcome results
None listed