- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04220775
Bintrafusp Alfa and Stereotactic Body Radiation Therapy for the Treatment of Recurrent or Second Primary Head and Neck Squamous Cell Cancer
Phase I/II Study of M7824 Plus Curative Intent Re-Irradiation With Stereotactic Body Radiation Therapy (SBRT) in Patients With Local-Regionally Recurrent Head and Neck Squamous Cell Carcinoma
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the safety, tolerability and feasibility of bintrafusp alfa (M7824) when administered together with stereotactic body radiation therapy (SBRT) reirradiation. (Lead In) II. To evaluate the progression-free survival (PFS) rate of M7824 plus SBRT reirradiation at 1 year. (Phase 2)
SECONDARY OBJECTIVES:
I. To evaluate the overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST).
II. To evaluate the 1-year locoregional control (LRC), locoregional failure-free survival (LFFS), distant metastasis (DM) and overall survival (OS) rates.
III. To evaluate acute and late toxicity using Common Terminology Criteria for Adverse Events (CTCAE) - version (v) 5.0.
IV. To evaluate fibrosis-related toxicities and functional outcomes. V. To evaluate patient reported outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI).
VI. To evaluate volumetric tumor regression rate and magnetic resonance imaging (MRI) kinetic biomarkers after M7824 plus SBRT.
VII. To compare quality-adjusted-life-years (QALY) between M7824 plus SBRT reirradiation and historic SBRT reirradiation control.
EXPLORATORY OBJECTIVE:
I. Biomarkers will be accessed in the tumor and blood samples and correlated with clinical outcomes and toxicity.
OUTLINE:
Patients receive bintrafusp alfa intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Beginning day 15 of cycle 1, patients also undergo SBRT over 5 fractions once every other day (QOD) for 2 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days and then every 6 months for 3 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Texas
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Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with histologically documented local-regional recurrent squamous cell carcinoma of the head and neck, or second primary squamous cell carcinoma of the head and neck
- Patients must be willing to undergo research biopsy for tissue collection at baseline and at disease progression
- Previous receipt of at least 30 Gy of radiation for head and neck squamous cell cancer (HNSCC) with overlapping fields
- Not eligible or poor candidate or patient refusal of surgery for recurrence
- Evaluable disease apparent on imaging (MRI or computed tomography [CT])
- 1 to 3 sites of recurrence (< 60 cm^3 per site, total volume < 100 cm^3)
- Eastern Cooperative Oncology Group (ECOG) = 0, 1, or 2
- White blood count (WBC) >= 2000/L
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
- Platelets >= 100,000 cells/mm^3
- Hemoglobin >= 9.0 g/dl; Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 9.0 g/dl is acceptable
- Serum creatinine =< 1.5 mg/dl or creatinine clearance (CC) >= 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (except patients with Gilbert syndrome who can have total bilirubin < 3.0 mg/dL)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the upper limit of normal
- Negative serum pregnancy test for women of childbearing potential and confirmation within 24 hours of first dose of study drug
Exclusion Criteria:
- Presence of distant metastases
- Less than six-month disease free interval from end of prior radiotherapy to the head and neck
- Prior receipt of anti-PD-1/L1
- Patients who are pregnant or breast feeding
- Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to: symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device; myocardial infarction within 3 months of registration
- Active autoimmune disorder or immunosuppression (including human immunodeficiency virus [HIV], but excluding endocrine abnormalities that are controlled with replacement medications)
- Active viral hepatitis
- Steroid therapy of greater than prednisone 10 mgs a day or equivalent
- Prior history of invasive non-head and neck cancer within two years, with the exception of screen detected prostate cancer treated with observation only, basal cell and squamous cell carcinoma of the skin, and micro-invasive resected cervical carcinoma
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (bintrafusp alfa, SBRT)
Patients receive bintrafusp alfa IV over 1 hour on days 1 and 15.
Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Beginning day 15 of cycle 1, patients also undergo SBRT over 5 fractions once QOD for 2 weeks in the absence of disease progression or unacceptable toxicity.
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Ancillary studies
Other Names:
Ancillary studies
Undergo SBRT
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival (PFS)
Time Frame: From treatment initiation until a recurrence, progression or occurrence or death, whichever comes first, assessed at 1 year
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Will use the methods of Gooley to estimate the cumulative incidence of PFS "events."
A PFS event is defined as death or disease progression, including locoregional recurrence/progression or distant metastases.
Logistic regression models will be used to evaluate the effects of the important patient clinical factors including treatment on PFS.
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From treatment initiation until a recurrence, progression or occurrence or death, whichever comes first, assessed at 1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate
Time Frame: Up to 3 years
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Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1.
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Proportional hazards regression may be employed for multivariate analysis on time-to-event outcomes.
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Up to 3 years
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Time to progression
Time Frame: Up to 1 year
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Local control is defined as absence of local failure.
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Proportional hazards regression may be employed for multivariate analysis on time-to-event outcomes.
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Up to 1 year
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Loco-regional failure free survival rate
Time Frame: From treatment initiation until local failure or death from any cause, whichever occurs first, assessed up to 1 year
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Local failure is defined as failure (recurrence or progression) within the prescribed radiation field, including failure within 2 cm of the radiation field.
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Proportional hazards regression may be employed for multivariate analysis on time-to-event outcomes.
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From treatment initiation until local failure or death from any cause, whichever occurs first, assessed up to 1 year
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Distant metastases rate
Time Frame: From treatment initiation until distance metastases or death from any cause, whichever occurs first, assessed up to 1 year
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The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Proportional hazards regression may be employed for multivariate analysis on time-to-event outcomes.
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From treatment initiation until distance metastases or death from any cause, whichever occurs first, assessed up to 1 year
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Overall survival rate
Time Frame: From treatment initiation until time to death from any cause, assessed up to 1 year
|
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Proportional hazards regression may be employed for multivariate analysis on time-to-event outcomes.
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From treatment initiation until time to death from any cause, assessed up to 1 year
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Incidence of acute and late adverse events
Time Frame: Up to 90 days following the last dose of bintrafusp alfa
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Will be accessed by the Common Terminology Criteria for Adverse Events 5.0.
Frequency count and percentage will be provided for categorical variables such as toxicity type and severity.
The chi-square test or the Fisher's exact test will be applied to evaluate the association between two categorical variables.
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Up to 90 days following the last dose of bintrafusp alfa
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Fibrosis-related toxicities
Time Frame: Up to 90 days following the last dose of bintrafusp alfa
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Frequency count and percentage will be provided for categorical variables such as toxicity type and severity.
The chi-square test or the Fisher's exact test will be applied to evaluate the association between two categorical variables.
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Up to 90 days following the last dose of bintrafusp alfa
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Fibrosis-related functional outcomes
Time Frame: Up to 24 months
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Up to 24 months
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Patient-reported outcome (PRO) measures of symptoms
Time Frame: Up to 24 months post reirradiation
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Will be measured using MD Anderson Symptom Inventory and assessed at the completion of reirradiation, and subsequently every +/- 3-months until 24-months post reirradiation.
Generalized linear models for the repeated measures analysis will be performed to assess the change in PROs overtime with important covariates including treatment in the models.
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Up to 24 months post reirradiation
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Volumetric tumor regression rate
Time Frame: Up to 3 years
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Up to 3 years
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Magnetic resonance imaging kinetic biomarkers
Time Frame: Up to 24 months
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Up to 24 months
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Quality-adjusted-life-years
Time Frame: Up to 24 months
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Will be measured between bintrafusp alfa plus stereotactic body radiation therapy (SBRT) reirradiation and historic SBRT reirradiation control.
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Up to 24 months
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Head and Neck Neoplasms
- Neoplasms, Squamous Cell
- Carcinoma
- Recurrence
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Antineoplastic Agents
- Atezolizumab
Other Study ID Numbers
- 2019-0608 (Other Identifier: M D Anderson Cancer Center)
- NCI-2019-07625 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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