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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|
Major Inclusion Criteria:
1. Biopsy proven metastatic melanoma or non-squamous NSCLC with at least one untreated
brain metastasis that is at least 5 mm AND twice the MRI slice thickness, but less
than 20 mm, which is asymptomatic and not requiring immediate local therapy or
2. Patients who have had prior resection or biopsy of a CNS metastasis will be required
to provide a paraffin embedded specimen from tumor taken at the time of surgery, if
3. Patients will be required to undergo biopsy or submit archival tumor tissue from a
systemic site of disease for correlative studies. When not feasible, this requirement
can be waived after discussion with the principal investigators.
4. PD-L1 expression in tumor tissue from any site is required for patients with NSCLC.
PDL1 expression will be analyzed by a Merck assay.
5. Adequate organ function.
6. ECOG performance status < 2.
7. Any number of previous treatments with the exception of previous inhibitors of PD-1 or
8. Life expectancy of at least 3 months.
9. Understanding and willingness to consent.
10. A history of radiotherapy for brain metastases is allowed, but any lesion present at
the time of WBRT or included in the stereotactic radiotherapy field will NOT be
considered evaluable unless documented to have progressed since treatment.
Overall Inclusion Criteria:
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 20 mm, that is asymptomatic and does not require local therapy at the time of
enrollment ("clinically evaluable lesion(s)"). An untreated brain metastasis is
defined as a lesion not present at the time of whole brain radiation therapy or
included in a stereotactic radiotherapy field (or within 2mm of a treated lesion), or
any lesion that is new or unequivocally progressing since prior radiation therapy.
2. ECOG performance status < 2
3. Any number of previous treatments with the exception of previous inhibitors of PD-1,
PDL1, 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.
4. Life expectancy of at least 3 months
5. A history of previously treated brain metastases is allowed, provided that at least 7
days have lapsed between radiation and initiation of pembrolizumab. Any brain
?20mm or causing symptoms must be treated with local therapy (i.e. radiation or
surgical resection, as clinically appropriate) prior to study enrollment. 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.
6. 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
must be obtained for PD-L1 testing. PD-L1 expression will be analyzed by a Merck
assay. PDL1 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.
7. 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.
8. 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
Subjects of childbearing potential are those who have not been surgically sterilized
or have not been free from menses for > 1 year.
9. 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.
Major Exclusion Criteria:
1. Symptomatic brain metastases at the time of initiation of systemic therapy.
2. Other systemic therapy within 14 days of initiation of study drug.
3. Use of corticosteroids to control CNS symptoms. Low-dose steroid use (?10 mg of
prednisone or equivalent) is allowed.
4. Presence of leptomeningeal disease.
5. Presence of active autoimmune disease. Autoimmune thyroid disease will be allowed if
thyroid function is within normal range.
Overall Exclusion Criteria:
1. Symptomatic brain metastases. Any neurologic symptoms present must have resolved with
local 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 or targeted small molecule therapy within 2 weeks prior to
start of treatment or who has not recovered (i.e., ? Grade 1 or at baseline) from
adverse events due to a previously administered agent. Previous radiation to
extracranial sites may be completed at any time prior to initiation of pembrolizumab.
1. Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting
2. 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 1 week prior to treatment on day 1 of cycle
1. 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
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 a history of (non-infectious) pneumonitis that required steroids or current
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
29. Has a history of (non-infectious) pneumonitis that required steroids, current
pneumonitis or evidence of interstitial lung disease.
|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