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Evaluating Penetrance of Anticancer Drugs in the Brain in Patients with Brain Cancer, ADePPT Trial
Trial Status: active
This phase I trial evaluates how effective certain drugs are at penetrating brain tumors in patients with primary brain cancer or solid tumor cancers that have spread beyond their original location to the brain (brain metastases) and who are planning to have a surgical procedure to have the brain tumor removed (resected) as part of their standard care. Some patients on this trial may also have a change (mutation) in their KRAS gene (KRAS G12C+). Usual treatment for patients with metastatic brain tumors require patients to undergo radiation therapy or surgery before receiving systemic therapies. This study wants to see how well treating patients with drugs before surgery works and evaluates drug activity in the brain. Giving drugs before surgery may work better in treating patients with metastatic brain cancer who are planning to have brain tumor surgery.
Inclusion Criteria
Adult patients >= 18 years of age with one or more brain tumors planned for neurosurgical resection/biopsy
Patients with concomitant leptomeningeal metastasis are eligible provided they have parenchymal brain neoplastic disease requiring resection/biopsy
For all cohorts: no limit on prior CNS radiation or systemic therapy
Karnofsky performance status (KPS) >= 60
Life expectancy > 12 weeks
Adequate treatment washout period from prior therapies to allow recovery from any prior treatment-related toxicities before enrollment in the judgment of the investigator
Absolute neutrophil count (ANC) >= 1.0 × 10^3/uL (granulocyte-colony stimulating factor administration is not allowed within 1 week prior to cycle 1 day 1 [C1D1]) (obtained =< 7 days prior to the first day of study treatment)
Platelet count >= 10.0 x 10^4/uL
* Note: Participants requiring ongoing transfusions or growth factor support to maintain platelet count >= 10.0 x 10^4/uL are not eligible (Platelet transfusion is not allowed within 1 week prior to C1D1) (obtained =< 7 days prior to the first day of study treatment)
Hemoglobin >= 7.0 g/dL (>= 8 g/dL in gastric cancer / gastroesophageal cancer indications)
* Note: Participants requiring ongoing transfusions or growth factor support to maintain hemoglobin >= 8.0 g/dL are not eligible (Red blood cell transfusion is not allowed within 1 week prior to C1D1) (obtained =< 7 days prior to the first day of study treatment)
Creatinine clearance >= 30 mL/min, as calculated using the Cockcroft-Gault equation (obtained =< 7 days prior to the first day of study treatment)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 × upper limit of normal (ULN) (< 5 x ULN in participants with liver metastases) (obtained =< 7 days prior to the first day of study treatment)
Total bilirubin =< 1.5 × ULN if no liver metastases or < 3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline (obtained =< 7 days prior to the first day of study treatment)
Substudy A: patients with metastatic cancer that has a history of KRAS G12C mutation
Exclusion Criteria
Known allergy or hypersensitivity to study treatment or any of the study drug excipients. For patients who are allergic to gadolinium-based agents may receive premedication as per institutional protocol or imaged without contrast at the discretion of the principal investigator; reactions will be managed per standard institutional protocol
Multiple primary malignancies within 3 years, with the exception of:
* Adequately resected non-melanoma skin cancer
* Carcinoma in situ of the cervix
* Smoldering pre-malignant or malignant conditions with minimal concern for CNS or extracranial progression during treatment such as chronic lymphocytic leukemia (CLL) or monoclonal gammopathy of undetermined significance (MGUS) based on the assessment of the treating provider
* Curatively treated in-situ disease
* Other solid tumors curatively treated
* For patients with metastatic breast cancer: contralateral breast cancer
Additional locations may be listed on ClinicalTrials.gov for NCT06807619.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Nelson Moss
Phone: 917-829-0529
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Nelson Moss
Phone: 917-829-0529
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Nelson Moss
Phone: 917-829-0529
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Nelson Moss
Phone: 917-829-0529
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Nelson Moss
Phone: 917-829-0529
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Nelson Moss
Phone: 917-829-0529
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Nelson Moss
Phone: 917-829-0529
PRIMARY OBJECTIVE:
I. To evaluate the brain tumor penetration of novel or precision cancer drugs.
SECONDARY OBJECTIVES:
I. To evaluate central nervous system (CNS) progression-free survival (CNS PFS) in patients who have continued the cancer drug(s) postoperatively.
II. To evaluate the safety of each cohort in patients who receive at least 1 dose of drug.
III. To evaluate wound complication rates in each cohort in patients who receive at least 1 dose of drug and undergo surgical resection/biopsy of a brain tumor.
EXPLORATORY OBJECTIVES:
I. To explore correlations between tumor-intrinsic features (i.e. size and contrast uptake) with drug penetration.
II. To describe the rates of surgical site progression, untreated-site, and de novo CNS parenchymal progression, leptomeningeal carcinomatosis development, and overall survival (OS) in patients who remain on the drug postoperatively.
III. To describe extracranial overall response rate (ORR), progression free survival (PFS), duration of response (DoR), and disease control rate (DCR) for patients with brain metastases.
IV. To explore correlations of plasma and cerebrospinal fluid (CSF)-derived cell-free deoxyribonucleic acid (cfDNA) genomic profiles with those of resected/biopsied tumors.
V. Where applicable, to spatially describe drug target expression and drug/drug surrogate distribution via immunohistochemistry and/or matrix-assisted laser desorption ionization (MALDI) imaging.
VI. To explore correlations between intra-brain tumor drug levels and surrogates of cytotoxicity (e.g. cleaved PARP).
VII. Where applicable, to describe drug resistance mechanisms in resected/biopsied brain tumors.
VIII. To evaluate efflux pump expression (P-glycoprotein, MRP1, BCRP) in resected/biopsied brain tumors using immunohistochemistry.
OUTLINE:
Patients receive drug/combination of interest (DCOI) before surgery and undergo standard of care brain tumor resection/biopsy on study. DCOI may be continued postoperatively until disease progression or unacceptable toxicity, at the discretion of the treating oncologist. Patients also undergo contrast enhanced magnetic resonance imaging (MRI) throughout the study and may undergo lumbar puncture (LP) and collection of blood, CSF, and/or tissue samples on study.
After completion of study treatment, patients are followed up as per standard of care guidelines for up to 24 months.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
