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|NCT02337686 : Pharmacodynamic Study of Pembrolizumab in Patients With Recurrent Glioblastoma|
|Ages||Min: 18 Years Max: N/A|
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 histologically confirmed World Health Organization Grade IV malignant glioma
(glioblastoma or gliosarcoma). Participants will be eligible if the original histology
was low-grade glioma and a subsequent histological diagnosis of glioblastoma or
variants is made.
4. Patients must be at first or second relapse and clinically require reoperation for
tumor progression within 4 to 6 weeks. Note: Relapse is defined as progression
following initial therapy (i.e., radiation, chemotherapy, or radiation+ chemotherapy).
If the participant had a surgical resection for relapsed disease and no antitumor
therapy instituted for up to 12 weeks, this is considered one relapse. For
participants who had prior therapy for a low grade glioma, the surgical diagnosis of a
high grade glioma will be considered first relapse.
5. Have measurable disease consisting of a minimal volume of 1 cm3.
6. Have provided tissue from an archival tissue sample or newly obtained core or
excisional biopsy of a tumor lesion.
7. Have a performance status of >/= 60 on the KPS.
8. Stable dose of steroids for 5 days, no more than 2 mg dexamethasone (or equivalent)
total per day
9. Demonstrate adequate organ function as defined in Table 1, all screening labs should
be performed within 14 days prior to registration. 1) Hematological : Absolute
neutrophil count (ANC) >/=1,500 /mcL; Platelets >/=100,000 / mcL; Hemoglobin >/= 9
g/dL or >/= 5.6 mmol/L. 2) Renal: Serum creatinine = 1.5 X upper limit of normal
(ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of
creatinine or CrCl) >/= 60 mL/min for subject with creatinine levels > 1.5 X
10. (9. continued) 3) Hepatic: Serum total bilirubin = 1.5 X ULN OR Direct bilirubin =
ULN for subjects with total bilirubin levels > 1.5 ULN; AST (SGOT) and ALT (SGPT) =
2.5 X ULN OR = 5 X ULN for subjects with liver metastases. 4) Coagulation:
International Normalized Ratio (INR) or Prothrombin Time (PT) = 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; 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.
11. Female subject of childbearing potential should have a negative serum pregnancy test.
12. 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.
13. 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.
1. Has been treated previously with bevacizumab
2. Has tumor localized primarily to the brainstem or spinal cord.
3. Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics
delivered by local injection or convection enhanced delivery.
4. Is currently participating in or has participated in a study of an investigational
agent or using an investigational device 4 weeks since last dose of agent
5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy > 2 mg of
dexamethasone total per day or any other form of immunosuppressive therapy within 7
days prior to the first dose of trial treatment.
6. Has had a prior monoclonal antibody 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.
7. 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 alopecia, = Grade 2 neuropathy are an exception to this criterion and may
qualify for the study.
8. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or in situ cervical cancer that has undergone potentially curative therapy.
9. Has known carcinomatous meningitis, extracranial disease, or multifocal disease.
10. Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or
resolved childhood asthma/atopy would be an exception to this rule. Subjects that
require intermittent use of bronchodilators or local steroid injections would not be
excluded from the study. Subjects with hypothyroidism stable on hormone replacement or
Sjorgen's syndrome will not be excluded from the study.
11. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
12. Has an active infection requiring systemic therapy.
13. 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.
14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
15. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.
16. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137
antibody (including ipilimumab or any other antibody or drug specifically targeting
T-cell co-stimulation or checkpoint pathways).
17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Testing not required.
18. Has known history of Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected). Testing not required.
19. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
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