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A Study of Oral IRAK-4 Inhibitor CA-4948 in Combination With Pembrolizumab Following Stereotactic Radiosurgery in Patients With Melanoma Brain Metastases

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Identifier: NCT05669352

Recruitment Status: Recruiting

Brief Summary:

Condition or disease

Intervention/treatment

Phase

Condition or disease

Melanoma Metastatic in the Brain

Intervention/treatment

CA-4948 and Pembrolizumab

Phase

Phase 1Phase 2

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This phase I/II trial will investigate the use of the novel oral IRAK-4 inhibitor CA-4948 in combination with pembrolizumab therapy following stereotactic radiosurgery in patients with melanoma brain metastases (MBM). The investigators hypothesize that the addition of CA-4948 will reduce the rate of distant intracranial failure and reduce the need for subsequent radiation therapy. The investigators also propose that it will have a significant reduction in radiation necrosis and improve patient-reported symptoms and quality of life. This trial represents the first time an oral IRAK-4 inhibitor has been used in combination with aPD1 therapy in MBM and will yield valuable insight into its synergistic potential both in MBM and additional sites of metastases.

Eligibility Criteria:

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Ages Eligible for Study: 18 Years - 99 Years

Sexes Eligible for Study: All

Inclusion Criteria:

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Inclusion Criteria:

Patients must have radiographic or histologically confirmed melanoma brain metastases (MBM) and be planning to undergo SRS for treatment
Patients must have measurable disease
Patients may be treatment-naïve or currently on therapy for systemic disease control at time of MBM development. If currently on therapy, patients must have at least stable disease (SD) systemically per RECIST criteria at the time of MBM diagnosis. If MBM diagnosis coincides with initial diagnosis, patients may be treatment-naïve with systemic disease.
Patients must have peripheral disease amenable to biopsy.
Patients must be tolerant of receiving MRI and cannot have intolerance to gadolinium contrast.
Age ≥18 years at time of informed consent.
ECOG performance status ≤1

Patients must have adequate organ and marrow function as defined below:

absolute neutrophil count ≥ 1,500/mcL
platelets ≥ 100,000/mcL
hemoglobin ≥ 9.0 g/dL or ≥5.6 mmol/L
coagulation PT/INR and aPTT ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic ranged of intended use for anticoagulants
total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) OR direct bilirubin no lower than the ULN if total bilirubin > 1.5 × ULN
AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN (with confirmed liver metastases: AST and ALT ≤ 5 x ULN)
creatinine clearance (CrCl)≤ 1.5 × ULN measured or calculated OR glomerular filtration rate (GFR)≥ 30 mL/min based on modified Cockcroft and Gault formula for participants with creatinine levels > 1.5 × institutional upper limit of normal (ULN)
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Subjects of childbearing potential must have a negative serum pregnancy test at screening and agree to use of highly effective methods of contraception throughout the study and for at least four months following the last dose of study treatment.
Subjects with partners of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation and 4 months after completion of CA-4948 administration. Subjects should also not donate sperm from first dose of therapy until 4 months after the last dose of treatment.
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Participants must have recovered from all adverse events due to previous therapies to ≤Grade 1 or baseline with the exception of alopecia.
Archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated has been provided.
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

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Exclusion Criteria:

Subject of child-bearing potential who has a positive urine pregnancy test within 72 hours prior to treatment
Subject has received prior systemic anti-cancer therapy including investigational agents or devices within 4 weeks prior to screening
If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
Prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids over ≤ 10mg of oral prednisone daily or equivalent, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. mRNA COVID-1 vaccines are allowed.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
Has severe hypersensitivity (≥Grade 3) to pembrolizumab, CA-4948, or any of their excipients.
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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
Has a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the trial’s requirements.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
Has had an allogenic tissue/solid organ transplant.
Unable to discontinue medications contraindicated to CA-4948 or pembrolizumab.
Patients with uncontrolled intercurrent illness.

Locations (0)


Moffitt Cancer Center
1320)
1322)

MAtch:1322 / 1322 /1950-Moffitt Cancer Center


This Location ALREADY exists:Moffitt Cancer Center
Winship Cancer Institute
1320)
1322)

MAtch:1322 / 1322 /1950-Winship Cancer Institute


This Location ALREADY exists:Winship Cancer Institute
Northwestern Memorial Hospital
1320)
1322)

MAtch:1322 / 1322 /1950-Northwestern Memorial Hospital


This Location ALREADY exists:Northwestern Memorial Hospital
University of Chicago Medical Center
1320)
1322)

MAtch:1322 / 1322 /1950-University of Chicago Medical Center


This Location ALREADY exists:University of Chicago Medical Center
Dana Farber Cancer Institute
1320)
1322)

MAtch:1322 / 1322 /1950-Dana Farber Cancer Institute


This Location ALREADY exists:Dana Farber Cancer Institute
Oncology Hematology West, PC dba Nebraska Cancer Specialists
1320)
1322)

MAtch:1322 / 1322 /1950-Oncology Hematology West, PC dba Nebraska Cancer Specialists


This Location ALREADY exists:Oncology Hematology West, PC dba Nebraska Cancer Specialists
Albert Einstein Medical College
1320)
1322)

MAtch:1322 / 1322 /1950-Albert Einstein Medical College


This Location ALREADY exists:Albert Einstein Medical College
University of Rochester Medical Center
1320)
1322)

MAtch:1322 / 1322 /1950-University of Rochester Medical Center


This Location ALREADY exists:University of Rochester Medical Center
Novant Health Hematology - Forsyth
1320)
1322)

MAtch:1322 / 1322 /1950-Novant Health Hematology - Forsyth


This Location ALREADY exists:Novant Health Hematology – Forsyth
The Ohio State University Wexner Medical Center - James Cancer Hospital
1320)
1322)

MAtch:1322 / 1322 /1950-The Ohio State University Wexner Medical Center - James Cancer Hospital


This Location ALREADY exists:The Ohio State University Wexner Medical Center – James Cancer Hospital
The University of Texas MD Anderson Cancer Center
1320)
1322)

MAtch:1322 / 1322 /1950-The University of Texas MD Anderson Cancer Center


This Location ALREADY exists:The University of Texas MD Anderson Cancer Center
Vseobecna Fakultni nemocnice v Praze
1320)
1322)

MAtch:1322 / 1322 /1950-Vseobecna Fakultni nemocnice v Praze


This Location ALREADY exists:Vseobecna Fakultni nemocnice v Praze
Service d'hématologie clinique CHU de Nice
1320)
1322)

MAtch:1322 / 1322 /1950-Service d'hématologie clinique CHU de Nice


This Location ALREADY exists:Service d’hématologie clinique CHU de Nice
APHP - Sorbonne Universite
1320)
1322)

MAtch:1322 / 1322 /1950-APHP - Sorbonne Universite


This Location ALREADY exists:APHP – Sorbonne Universite
APHP - Hopital Saint Louis
1320)
1322)

MAtch:1322 / 1322 /1950-APHP - Hopital Saint Louis


This Location ALREADY exists:APHP – Hopital Saint Louis
Marien Hospital Dusseldorf; Klinik fur Onkologie und Hamatologie, Palliativmedizin
1320)
1322)

MAtch:1322 / 1322 /1950-Marien Hospital Dusseldorf; Klinik fur Onkologie und Hamatologie, Palliativmedizin


This Location ALREADY exists:Marien Hospital Dusseldorf; Klinik fur Onkologie und Hamatologie, Palliativmedizin
Universitatsklinikum Leipzig; Medizinische Klinik und Poliklinik I
1320)
1322)

MAtch:1322 / 1322 /1950-Universitatsklinikum Leipzig; Medizinische Klinik und Poliklinik I


This Location ALREADY exists:Universitatsklinikum Leipzig; Medizinische Klinik und Poliklinik I
Klinikum rechts der Isar der Technischen Universitat Munchen
1320)
1322)

MAtch:1322 / 1322 /1950-Klinikum rechts der Isar der Technischen Universitat Munchen


This Location ALREADY exists:Klinikum rechts der Isar der Technischen Universitat Munchen
Universitatsklinikum Munster
1320)
1322)

MAtch:1322 / 1322 /1950-Universitatsklinikum Munster


This Location ALREADY exists:Universitatsklinikum Munster
Soroka University MC
1320)
1322)

MAtch:1322 / 1322 /1950-Soroka University MC


This Location ALREADY exists:Soroka University MC
Edith Wolfson Medical Center
1320)
1322)

MAtch:1322 / 1322 /1950-Edith Wolfson Medical Center


This Location ALREADY exists:Edith Wolfson Medical Center
Hadassah University MC
1320)
1322)

MAtch:1322 / 1322 /1950-Hadassah University MC


This Location ALREADY exists:Hadassah University MC
Azienda Ospedaliera Santa Croce e Carle
1320)
1322)

MAtch:1322 / 1322 /1950-Azienda Ospedaliera Santa Croce e Carle


This Location ALREADY exists:Azienda Ospedaliera Santa Croce e Carle
Instituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
1320)
1322)

MAtch:1322 / 1322 /1950-Instituto Romagnolo per lo Studio dei Tumori "Dino Amadori"


This Location ALREADY exists:Instituto Romagnolo per lo Studio dei Tumori "Dino Amadori"
Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
1320)
1322)

MAtch:1322 / 1322 /1950-Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz


This Location ALREADY exists:Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
University Hospital in Krakow
1320)
1322)

MAtch:1322 / 1322 /1950-University Hospital in Krakow


This Location ALREADY exists:University Hospital in Krakow
Hospital de la Santa Creu I Sant Pau (Neuvo Hospital)
1320)
1322)

MAtch:1322 / 1322 /1950-Hospital de la Santa Creu I Sant Pau (Neuvo Hospital)


This Location ALREADY exists:Hospital de la Santa Creu I Sant Pau (Neuvo Hospital)
Hospital Universitaro del a Princesa
1320)
1322)

MAtch:1322 / 1322 /1950-Hospital Universitaro del a Princesa


This Location ALREADY exists:Hospital Universitaro del a Princesa
MD Anderson Cancer Center Madrid
1320)
1322)

MAtch:1322 / 1322 /1950-MD Anderson Cancer Center Madrid


This Location ALREADY exists:MD Anderson Cancer Center Madrid
Hospital Universitario Virgen del Rocio
1320)
1322)

MAtch:1322 / 1322 /1950-Hospital Universitario Virgen del Rocio


This Location ALREADY exists:Hospital Universitario Virgen del Rocio1