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|NCT02681549 : Pembrolizumab Plus Bevacizumab for Treatment of Brain Metastases in Metastatic Melanoma or Non-small Cell Lung Cancer|
|Ages||Min: 18 Years Max: N/A|
1. Biopsy proven metastatic melanoma or non-squamous NSCLC with at least one untreated
cerebral metastasis that is at least 5 mm AND twice the MRI slice thickness, but less
than Page 22 of 71 20 mm, that is asymptomatic and does not require local therapy at
the time of enrollment ("clinically evaluable lesion(s)").
2. Age ?18
3. ECOG performance status < 2
4. Any number of previous treatments with the exception of previous inhibitors of PD-1,
PD-L1, or PD-L2. Other prior systemic therapies must have been administered at least 2
weeks before administration of pembrolizumab; the exception to this is ipilimumab
which must have been administered at least 4 weeks prior to the start of
pembrolizumab. Patients are not required to have had prior systemic therapy.
5. Life expectancy of at least 3 months
6. A history of previously treated brain metastases is allowed, provided that at least 14
days have lapsed between radiation and initiation of pembrolizumab. Any lesion present
at the time of WBRT or included in the stereotactic radiotherapy field (or within 2mm
of the treated lesion) will NOT be considered evaluable unless it is new or documented
to have progressed since treatment.
7. PD-L1 expression in tumor tissue from any site is required for patients with NSCLC.
Tumor tissue can be archival, however if no archival tissue is available then a biopsy
mube obtained for PD-L1 testing. PD-L1 expression will be analyzed by a Merck assay.
PD-L1 expression is not required for patients with melanoma, but melanoma patients are
required to submit an extra-cerebral specimen for analysis, unless it is not feasible
to obtain one.
8. Patients must have normal organ and marrow function Exclusion Criteria:
9. 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.
10. 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.
11. 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. Symptomatic brain metastases. Any neurologic symptoms present must have resolved
withlocal therapy by the time of administration of study drug.
2. Patients with brain metastases for whom complete surgical resection is clinically
3. Patients with lung cancer with squamous histology.
4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy to
the lung or brain 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.
Previous radiation to other sites may be completed at any time prior to initiation of
pembrolizumab. Note: If subject received major surgery, they must have recovered
adequately from the toxicity and/or complications from the intervention prior to
Note: Toxicity that has not recovered to ? Grade 1 is allowed if it meets the
inclusion requirements for laboratory parameters.
5. Has had prior treatment with any other anti-PD-1 or PD-L1 or PD-L2 agent.
6. The use of corticosteroids to control cerebral edema or treat neurologic symptoms will
not be allowed, and patients who previously required corticosteroids for symptom
control must be off steroids for at least 2 weeks. Low-dose steroid use (?10 mg of
prednisone or equivalent) as corticosteroid replacement therapy is allowed
7. Has not recovered (i.e., ? Grade 1 or at baseline) from adverse events due to agents
administered more than 4 weeks earlier.
8. Presence of leptomeningeal disease
9. Has active autoimmune disease that has required systemic treatment in the past 2 years
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. Pregnancy or breast feeding. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she should inform her treating physician
immediately. Because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding
must be discontinued if the mother is treated with pembrolizumab.
11. Patients may not be receiving any other investigational agents and may not have
participated in a study of an investigational agent or using an investigational device
within 4 weeks of the first dose of treatment.
12. Either a concurrent condition (including medical illness, such as active infection
requiring treatment with intravenous antibiotics or the presence of laboratory
abnormalities) or history of a prior condition that places the patient at unacceptable
risk if he/she were treated with the study drug or a medical condition that confounds
the ability to interpret data from the study.
13. Concurrent, active malignancies in addition to those being studied (other than
cutaneous squamous cell carcinoma or basal cell carcinoma)
14. Patients with active hemoptysis.
15. Any contraindication to MRI (i.e. patients with pacemakers or other metal implanted
medical devices). An MRI safety questionnaire is required prior to MR imaging.
16. Has active non-infectious pneumonitis
17. Has a known Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or Hepatitis C
18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
19. Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg
and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy to achieve
these parameters is allowable.
20. History of myocardial infarction or unstable angina within 3 months prior to Cycle 1,
21. History of stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1
22. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1
23. Evidence of bleeding diathesis or clinically significant coagulopathy (in the absence
of therapeutic anticoagulation). Any history of significant bleeding or thrombosis
should be discussed the study PIs.
24. Current or recent (within 10 calendar days prior to Cycle 1, Day 1) use of
dipyramidole, ticlopidine, clopidogrel, or cilostazol
25. Warfarin is not permitted. Prophylactic or therapeutic use of low molecular-weight
heparin (e.g., enoxaparin) or direct thrombin inhibitors are permitted.
26. History of abdominal or tracheoesophageal fistula or gastrointestinal perforation
within 6 months prior to Cycle 1, Day 1
27. Serious, non-healing or dehiscing wound
28. Proteinuria > 2.0 g of protein in a 24-hour urine collection. All patients with 2
protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for
|Links||Permanent Link to THIS page: http://virtualtrials.com/nct/display1trial.cfm?nct=NCT02681549
| Link to official Clinicaltrials.gov listing
Facility: Smilow Cancer Hospital at Yale New Haven
Harriet Kluger, MD
Email not avaialable