Ignite Creation Date:
2025-12-24 @ 5:46 PM
Ignite Modification Date:
2026-01-01 @ 5:52 PM
Study NCT ID:
NCT04789668
Status:
COMPLETED
Last Update Posted:
2024-12-13
First Post:
2021-02-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Bintrafusp Alfa and Pimasertib for the Treatment of Patients With Brain Metastases
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
Phase I/II Trial of BINTRAFUSP ALFA (M7824) and Pimasertib for Treatment of Intracranial Metastases
Status:
COMPLETED
Status Verified Date:
2024-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I/II trial studies the best dose and effect of pimasertib in combination with bintrafusp alfa in treating patients with cancer that has spread to the brain (brain metastases). Immunotherapy with bintrafusp alfa, a bifunctional fusion protein composed of the monoclonal antibody anti-PD-L1 and TGF-beta, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pimasertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pimasertib and bintrafusp alfa may help to prevent or delay the cancer from progressing (getting worse) and/or coming back.
Detailed Description:
PRIMARY OBJECTIVES:
I. Establish safety profile and recommended phase II dose for combining pimasertib with bintrafusp alfa (M7824) in patients with brain metastases. (Phase I)
II. Time to intracranial progression (defined as progression of existing lesions and development of new lesions by modified Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1). (Phase II)
III. Overall survival. (Phase II)
SECONDARY OBJECTIVES:
I. Intracranial progression 6, 12 and 18 months.
II. Intracranial objective response rate as measured by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM), immunotherapy (i)RANO, and RECIST 1.1.
III. Time to second intracranial progression after salvage stereotactic radiosurgery (SRS).
IV. Overall survival rate at 6, 12 and 18 months.
V. Frequency of grade 3+ intracranial toxicities at 4 weeks, and 3, 6, 9, 12 and 18 months.
VI. Frequency of extracranial progression and response rate at 8 weeks, and 3, 6, 9, 12 and 18 months.
VII. Frequency of neurocognitive decline at 6, 12 and 18 months (optional).
VIII. Changes in neurocognitive function and health-related quality of life.
IX. Dose, duration and frequency of steroid use for symptomatic management.
EXPLORATORY OBJECTIVES:
I. Identify molecular and/or immunological markers from biospecimens (tissue, blood, and cerebrospinal fluid \[CSF\]) that are associated with treatment response and toxicity.
II. Identify imaging biomarkers of response and toxicity (acute radiation effect/radionecrosis and neurocognitive changes) from multiparametric magnetic resonance imaging (MRI) and/or delayed positron emission tomography (PET) that predict treatment response and toxicity.
III. Identify correlative or surrogative relationship between systemic (blood) and imaging markers and treatment outcomes.
OUTLINE: This is a phase I, dose-escalation study of followed by a phase II dose-expansion study.
Patients receive bintrafusp alfa intravenously (IV) over 1 hour every 2 weeks and pimasertib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, every 6 weeks during year 1, and then every 12 weeks for up to 2 years.
I. Establish safety profile and recommended phase II dose for combining pimasertib with bintrafusp alfa (M7824) in patients with brain metastases. (Phase I)
II. Time to intracranial progression (defined as progression of existing lesions and development of new lesions by modified Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1). (Phase II)
III. Overall survival. (Phase II)
SECONDARY OBJECTIVES:
I. Intracranial progression 6, 12 and 18 months.
II. Intracranial objective response rate as measured by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM), immunotherapy (i)RANO, and RECIST 1.1.
III. Time to second intracranial progression after salvage stereotactic radiosurgery (SRS).
IV. Overall survival rate at 6, 12 and 18 months.
V. Frequency of grade 3+ intracranial toxicities at 4 weeks, and 3, 6, 9, 12 and 18 months.
VI. Frequency of extracranial progression and response rate at 8 weeks, and 3, 6, 9, 12 and 18 months.
VII. Frequency of neurocognitive decline at 6, 12 and 18 months (optional).
VIII. Changes in neurocognitive function and health-related quality of life.
IX. Dose, duration and frequency of steroid use for symptomatic management.
EXPLORATORY OBJECTIVES:
I. Identify molecular and/or immunological markers from biospecimens (tissue, blood, and cerebrospinal fluid \[CSF\]) that are associated with treatment response and toxicity.
II. Identify imaging biomarkers of response and toxicity (acute radiation effect/radionecrosis and neurocognitive changes) from multiparametric magnetic resonance imaging (MRI) and/or delayed positron emission tomography (PET) that predict treatment response and toxicity.
III. Identify correlative or surrogative relationship between systemic (blood) and imaging markers and treatment outcomes.
OUTLINE: This is a phase I, dose-escalation study of followed by a phase II dose-expansion study.
Patients receive bintrafusp alfa intravenously (IV) over 1 hour every 2 weeks and pimasertib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, every 6 weeks during year 1, and then every 12 weeks for up to 2 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: