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A Phase II Study of MK-3475 in Patients with Metastatic Melanoma or Non-Small Cell Lung Cancer with Untreated Brain Metastases

Conditions

Lung | Melanoma, skin

Trial Phase

Phase II

Trial Purpose and Description

Trial Purpose

The purpose of this trial is to study the activity of MK-3475 in untreated brain metastases from melanoma or non-small cell lung cancer.


Participation Guidelines

Age:
Gender:
Both

Eligibility Criteria

Inclusion Criteria:

  1. Biopsy proven metastatic melanoma or NSCLC:

    1. Patients with metastatic melanoma must have at least two untreated brain metastases including:

      • At least one cerebral metastasis that requires local intervention and is amenable to craniotomy or LITT therapy either due to symptoms, lesion size, location, edema or hemorrhage ("surgical lesion"). Alternatively, a patient may be eligible if one or more cerebral metastases was resected prior to enrollment and there is tumor tissue available for analysis.
      • At least one ADDITIONAL cerebral metastasis that is at least 5 mm OR 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)").

      OR

    2. Patients with stage IV NSCLC with at least one cerebral metastasis that is at least 5 mm OR 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)").
  2. Age >18
  3. Adequate organ function
  4. ECOG performance status < 2
  5. Any number of previous treatments with the exception of previous inhibitors of PD-1 other prior systemic therapies must have been administered at least 2 weeks before administration of MK-3475
  6. Life expectancy of at least 3 months
  7. A history of radiotherapy for brain metastases is allowed, provided that at least 14 days have lapsed prior to initiation of MK-3475. 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.
  8. PD-L1 expression in at least 5% of cells from tumor tissue from any site is required for patients with NSCLC. PD-L1 expression is not required for patients with melanoma. Expression with determined by Merck using an in-house assay.
  9. Patients must have normal organ and marrow function:
  10. For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of MK-3475.
  11. For men with female partners of childbearing potential, agreement to use a latex condom, and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of MK-3475.
  12. Negative serum or urine pregnancy test within 7 days of commencement of treatment in premenopausal women.
  13. Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Symptomatic brain metastases. Symptoms may be present from the surgical lesion prior to resection or LITT but must resolve following local therapy (ie symptoms should not be attributable to the clinically evaluable lesions)
  2. Radiotherapy or local therapy within 14 days of enrollment
  3. The use of corticosteroids to control cerebral edema or treat neurologic symptoms will not be allowed. Low-dose steroid use (&le10 mg of prednisone or equivalent) as corticosteroid replacement therapy 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
  6. Pregnancy or breast feeding.
  7. Patients may not be receiving any other investigational agents.
  8. 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.
Sponsor:
Yale Cancer Center
Dates:
03/31/2014
Last Updated:
Study HIC#:
1401013290