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
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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
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2027
March 12, 2024
March 1, 2024
10.2 years
August 29, 2016
March 8, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Objective Response Rate
Contrast-enhanced cranial MRI will be performed every 6 weeks. 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.
6 Weeks
Overall Survival Rate
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 six 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
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.
3 Months
Secondary Outcomes (6)
Number of Participants with grade-3 or higher hematologic toxicities or grade-3 or higher neurologic toxicities
Baseline to 21 Days
Overall Survival Rate
3 Months and 6 Months
Intracranial Response Rate
6 Months
Extracranial Response Rate
6 Months
Extracranial PFS
3 Months and 6 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
- Massachusetts General Hospitallead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (2)
Priscilla Brastianos
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)
Study Officials
- PRINCIPAL INVESTIGATOR
Priscilla Brastianos, MD
Massachusetts General Hospital
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)
December 1, 2026
Study Completion (Estimated)
December 1, 2027
Last Updated
March 12, 2024
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will not share