Bintrafusp Alfa and Pimasertib for the Treatment of Patients With Brain Metastases
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|ClinicalTrials.gov Identifier: NCT04789668|
Recruitment Status : Recruiting
First Posted : March 9, 2021
Last Update Posted : March 12, 2021
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage IV Breast Cancer AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Hematopoietic and Lymphoid Cell Neoplasm Hormone Receptor Positive Breast Adenocarcinoma Metastatic Lung Non-Small Cell Carcinoma Metastatic Malignant Neoplasm in the Brain Metastatic Malignant Solid Neoplasm Metastatic Melanoma Metastatic Triple-Negative Breast Carcinoma Pathologic Stage IV Cutaneous Melanoma AJCC v8 Prognostic Stage IV Breast Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8||Drug: Bintrafusp Alfa Drug: Pimasertib Other: Quality-of-Life Assessment||Phase 1 Phase 2|
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)
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.
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial of BINTRAFUSP ALFA (M7824) and Pimasertib for Treatment of Intracranial Metastases|
|Actual Study Start Date :||January 15, 2021|
|Estimated Primary Completion Date :||May 1, 2025|
|Estimated Study Completion Date :||May 1, 2025|
Experimental: Treatment (bintrafusp alfa, pimasertib)
Patients receive bintrafusp alfa IV over 1 hour every 2 weeks and pimasertib PO BID on days 1-28. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Drug: Bintrafusp Alfa
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Clinical benefit rate [ Time Frame: Up to 2 years ]
- Incidence of intracranial and extracranial toxicities and dose-limiting toxicities (Phase I) [ Time Frame: Up to 90 days ]Will be summarized by grade, relationship, time during the treatment, etc., for each dose in each group.
- Recommended phase II dose (Phase I) [ Time Frame: At 4 weeks after first administration of treatment ]The recommended phase II dose is defined as the highest dose level with no more than 1 patient with dose-limiting toxicity out of 6 patients that are treated.
- Time to intracranial progression (Phase II) [ Time Frame: From the time of study enrollment to intracranial progression (event) or the last follow-up date if the patient has not developed the intracranial progression yet, assessed up to 2 years ]Will be determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and estimated using Kaplan-Meier method with 95% confidence interval.
- Overall survival (Phase II) [ Time Frame: From treatment start date to death, assessed up to 2 years ]Will be estimated using Kaplan-Meier method, both with 95% confidence interval.
- Intracranial progression [ Time Frame: From the time of study enrollment to intracranial progression (event) or the last follow-up date if the patient has not developed the intracranial progression yet, assessed up to 18 months ]Will be determined by modified RECIST 1.1 and estimated and reported with 95% confidence interval utilizing the method of Kaplan and Meier. Will be performed overall and within each treatment group. Completing risk analysis may be considered by treating events outside of intracranial disease progression (e.g. events such as extracranial disease progression, early dropout due to toxicity, or death) as competing risks.
- Time to extracranial progression [ Time Frame: From the time of study enrollment to extracranial progression (event) or thelast follow-up date if the patient has not developed the extracranial progression yet, assessed up to 18 months ]Will be determined by modified RECIST 1.1. The cumulative incidence rate may be estimated by competing risk analysis treating events outside of extracranial disease progression (e.g. events such as intracranial disease progression, early dropout due to toxicity, or death) as competing risks.
- Best achieved extracranial objective response rate [ Time Frame: Up to 2 years ]Will be reported for each patient. The frequency of extracranial objective response will be reported overall and within each treatment group.
- Duration of response [ Time Frame: From date of first imaging identifying partial response (PR) or complete response (CR) until the date of first imaging identifying progressive disease is noted, assessed up to 2 years ]Will be assessed in patients who achieve extracranial, PR or CR via RECIST 1.1 criteria and calculated utilizing the Kaplan-Meier method with reporting of the median and range overall and within each treatment group.
- Dose, duration and frequency of steroid use for symptomatic management [ Time Frame: Up to 2 years ]Will record and report steroid requirements for symptom management overall and within each treatment group. Patients who require at least 4 mg of dexamethasone/day for symptom management will be considered as requiring high dose steroids.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04789668
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Hussein A. Tawbi 713-792-2921 HTawbi@mdanderson.org|
|Principal Investigator: Hussein A. Tawbi|
|Principal Investigator:||Hussein A Tawbi||M.D. Anderson Cancer Center|