Pembrolizumab In Central Nervous System Metastases
Phase II Trial of Pembrolizumab in Central Nervous System Metastases From Multiple Histologies
1 other identifier
interventional
101
1 country
2
Brief Summary
This research study is studying Pembrolizumab as a possible treatment for this diagnosis for metastases in the central nervous system (brain and spinal cord).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2016
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 29, 2016
CompletedFirst Posted
Study publicly available on registry
September 1, 2016
CompletedStudy Start
First participant enrolled
October 1, 2016
CompletedResults Posted
Study results publicly available
June 26, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2028
July 21, 2026
July 1, 2026
10.7 years
August 29, 2016
March 10, 2026
July 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Intracranial Benefit Rate (Cohorts A and B)
Contrast-enhanced cranial MRI will be performed every 6 weeks. Intracranial benefit rate is defined as the percentage of patients with complete response (CR), partial response (PR), or stable disease (SD) by RANO (Response assessment in neuro-oncology) criteria for brain metastases. CR is defined as the complete disappearance of all disease sustained for at least 4 weeks. PR is defined as greater than or equal to 30% decrease compared to baseline in the sum of target lesions sustained for at least 4 weeks and no progression of non-measurable disease. Stable disease is defined as not qualifying for CR, PR, or disease progression. The proportion of patients in each cohort with a best response of CR or PR will be presented with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
44 months
Overall Survival at Three Months (Cohort C)
Overall survival at three months is defined as the proportion of patients alive three months after enrollment. Any patient whose vital status is unknown due to loss of follow-up will be classified as having died for purposes of estimating the primary endpoint. The proportion of patients alive at three months will be summarized with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
3 Months
Extracranial Overall Response Rate (Cohort D)
The proportion of patients with a best extracranial response of CR or PR will be presented with a 90% confidence interval estimated using the method of Atkinson and Brown, which allows for the two-stage design.
Data collection is ongoing for this objective. The longest time a single patient has been followed for this measure is 6 years.
Secondary Outcomes (6)
Number of Participants With Grade-3 or Higher Toxicities at Least Possibly Related to Treatment (Cohorts A, B, C, D)
Up to 44 months
Median Overall Survival (Cohorts A, B, D)
Up to 54 months
Intracranial Response Rate (Cohort C)
16 months
Extracranial Response Rate (Cohorts A and B Combined, C)
44 months
Extracranial Progression Free Survival (Cohorts A, B, C, D)
Up to 44 months
- +1 more secondary outcomes
Study Arms (4)
Previously Untreated Brain Metastases-Cohort A
EXPERIMENTAL\- Previously Untreated Brain Metastases * Baseline Brain MRI and PET CT * For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis. * Brain MRI and PET/CT
Progressive Brain Metastases-Cohort B
EXPERIMENTAL\- Progressive Brain Metastases * Baseline Brain MRI and PET CT * For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis. * Brain MRI and PET/CT
Neoplastic Meningitis-Cohort C
EXPERIMENTAL* Neoplastic Meningitis * Histologically confirmed solid malignancy * Positive Cytology * Baseline Brain MRI * For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis. * Brain MRI and PET/CT
1-4 Brain Metastases from Melanoma Cohort D
EXPERIMENTAL* 1-4 Brain Metastases from Melanoma * Clinical indication for stereostatic radiosurgery * Evaluable extracranial focus * For all cohorts, pembrolizumab will be administered every 3 weeks, with 21 consecutive days defined as a treatment cycle. In Cohort D, cycle 1 and 2 of pembrolizumab will be administered 3 weeks apart and stereotactic radiosurgery will be administered between cycles. Treatment will be administered on an outpatient basis. * Brain MRI and PET CT
Interventions
Eligibility Criteria
You may qualify if:
- Participants must have histologically or cytologically confirmed disease from any solid tumor
- Participants must have measurable disease in the CNS, defined as at least one lesion that can be accurately measured in at least one dimension as ≥5 mm .
- Age ≥18 years.
- ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A)
- Life expectancy of greater than 6 weeks
- Participants must have normal organ and marrow function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
- Adequate Organ Function Laboratory Values
- Hematological
- \---- Absolute neutrophil count (ANC) ≥1,500 /mcL
- \---- Platelets ≥100,000 / mcL
- \---- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
- Renal
- \---- Serum creatinine ≤1.5 X upper limit of normal (ULN)
- \----- OR
- \---- Measured or calculated a creatinine clearance ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl)
- +36 more criteria
You may not qualify if:
- Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Participants who are receiving any other investigational agents.
- Has a diagnosis of immunodeficiency.
- Requires treatment with high dose systemic corticosteroids defined as dexamethasone \>2mg/day or bioequivalent within 7 days of initiating therapy.
- Has received systemic immunosuppressive treatments, aside from systemic corticosteroids as described in Section 3.2.4, within three months of start of study drug
- Hypersensitivity to pembrolizumab or any of its excipients
- Has a known history of active TB (Bacillus Tuberculosis)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. 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.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Merck Sharp & Dohme LLCcollaborator
- Massachusetts General Hospitallead
Study Sites (2)
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Related Publications (2)
Brastianos PK, Kim AE, Giobbie-Hurder A, Lee EQ, Lin NU, Overmoyer B, Wen PY, Nayak L, Cohen JV, Dietrich J, Eichler A, Heist RS, Krop I, Lawrence D, Ligibel J, Tolaney S, Mayer E, Winer E, Bent B, de Sauvage MA, Ijad N, Larson JM, Marion B, Nason S, Murthy N, Ratcliff S, Summers EJ, Mahar M, Shih HA, Oh K, Cahill DP, Gerstner ER, Sullivan RJ. Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results. Nat Med. 2023 Jul;29(7):1728-1737. doi: 10.1038/s41591-023-02392-7. Epub 2023 Jun 2.
PMID: 37268724DERIVEDBrastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nat Med. 2020 Aug;26(8):1280-1284. doi: 10.1038/s41591-020-0918-0. Epub 2020 Jun 2.
PMID: 32483359DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Analyses for cohorts A, B, and C are complete. Results for cohort D are still pending, as 2 patients are still in follow up.
Results Point of Contact
- Title
- Priscilla Brastianos, MD
- Organization
- Massachusetts General Hospital
Study Officials
- PRINCIPAL INVESTIGATOR
Nancy Wang, MD, MPH
Massachusetts General Hospital
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator/ Physician, Cancer Center
Study Record Dates
First Submitted
August 29, 2016
First Posted
September 1, 2016
Study Start
October 1, 2016
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
June 1, 2028
Last Updated
July 21, 2026
Results First Posted
June 26, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will not share