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MK-3475 in Melanoma and NSCLC Patients With Brain Metastases

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ClinicalTrials.gov Identifier: NCT02085070
Recruitment Status : Recruiting
First Posted : March 12, 2014
Last Update Posted : February 1, 2017
Information provided by (Responsible Party):
Yale University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Melanoma Non-Small Cell Lung Cancer Brain Metastases Drug: MK-3475 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of MK-3475 in Patients With Metastatic Melanoma and Non-Small Cell Lung Cancer With Untreated Brain Metastases
Study Start Date : March 2014
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Melanoma patients
After establishing eligibility criteria, for patients with melanoma the investigator will determine at least one lesion that requires local therapy (surgical resection or LITT) based on size, location, and/or risk of hemorrhage; this will be considered the "surgical lesion". All other eligible brain lesions will be considered "clinically evaluable lesions" and will be followed by modified RECIST (mRECIST) criteria to determine best response.
Drug: MK-3475
IV MK-3475
Non-small cell lung cancer patients
NSCLC patients are not required to have a "surgical lesion" but must have at least one "clinically evaluable lesion" in the central nervous system. Patients on NSCLC are required to have formalin-fixed, paraffin-embedded tumor tissue available for biomarker analysis.
Drug: MK-3475
IV MK-3475

Primary Outcome Measures :
  1. Response will be evaluated after systemic therapy [ Time Frame: 8 weeks ]
    Response will be evaluated after 8 weeks of systemic therapy and then every 8 weeks thereafter. The purpose of the 4 weeks scans is to determine safety. If sysmptoms develop or clinical deterioration occurs, patients may be imaged prior to the pre-specified time points for imaging. All responses must be confirmed by repeat imaging at least 4 weeks following initial documentation of objective response.

Secondary Outcome Measures :
  1. Brain metastases response assessment [ Time Frame: 28 days ]
    RECIST criteria v1.1 will be modified to account for differences in measuring the response of clinically evaluable brain lesions as opposed to systemic lesions (modified RECIST, or mRECIST). Size is considered the tumor's largest diameter. Measurements from multiple lesions are summed to calculate the sum of the diameters (SD). The SD calculated on a baseline scan performed within 28 days of study drug initiation will be used as a reference to determine the objective response of the clinically evaluable lesions. All responses must be confirmed at 4 weeks with an equivalent or better response. Please refer to the original RECIST criteria if further reference is necessary.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)").


    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 (≤10 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.
  9. Concurrent, active malignancies (other than cutaneous squamous cell carcinoma or basal cell carcinoma)
  10. 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.
  11. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  12. Evidence of interstitial lung disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02085070

United States, Connecticut
Smilow Cancer Center at Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Harriet Kluger, MD    203-737-2572    harriet.kluger@yale.edu   
Principal Investigator: Harriet Kluger, MD         
Sub-Investigator: Veronica Chiang, MD         
Sub-Investigator: Sarah Goldberg, MD         
Sub-Investigator: Roy Herbst, MD         
Sub-Investigator: Mario Sznol, MD         
Sub-Investigator: Scott Gettinger, MD         
Sub-Investigator: Anne Chiang, MD         
Sub-Investigator: Rogerio Lilenbaum, MD         
Sponsors and Collaborators
Yale University
Principal Investigator: Harriet Kluger, MD Yale University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02085070     History of Changes
Other Study ID Numbers: 1401013290
IND 121564 ( Other Identifier: FDA )
First Posted: March 12, 2014    Key Record Dates
Last Update Posted: February 1, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Brain Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antineoplastic Agents