Back to resultsBintrafusp Alfa and Stereotactic Body Radiation Therapy for the Treatment of Recurrent or Second Primary Head and Neck Squamous Cell Cancer
Primary Purpose
Recurrent Head and Neck Squamous Cell Carcinoma, Second Primary Squamous Cell Carcinoma of the Head and Neck
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bintrafusp Alfa
Quality-of-Life Assessment
Questionnaire Administration
Stereotactic Body Radiation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Head and Neck Squamous Cell Carcinoma
Eligibility Criteria
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
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (bintrafusp alfa, SBRT)
Arm Description
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.
Outcomes
Primary Outcome Measures
Progression-free survival (PFS)
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.
Secondary Outcome Measures
Overall response rate
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.
Time to progression
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.
Loco-regional failure free survival rate
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.
Distant metastases rate
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.
Overall survival rate
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.
Incidence of acute and late adverse events
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.
Fibrosis-related toxicities
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.
Fibrosis-related functional outcomes
Patient-reported outcome (PRO) measures of symptoms
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.
Volumetric tumor regression rate
Magnetic resonance imaging kinetic biomarkers
Quality-adjusted-life-years
Will be measured between bintrafusp alfa plus stereotactic body radiation therapy (SBRT) reirradiation and historic SBRT reirradiation control.
Full Information
NCT ID
NCT04220775
First Posted
November 26, 2019
Last Updated
October 27, 2022
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04220775
Brief Title
Bintrafusp Alfa and Stereotactic Body Radiation Therapy for the Treatment of Recurrent or Second Primary Head and Neck Squamous Cell Cancer
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
March 18, 2020 (Actual)
Primary Completion Date
October 3, 2022 (Actual)
Study Completion Date
October 3, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase I/II trial studies the side effects and how well bintrafusp alfa and stereotactic body radiation therapy work in treating patients with head and neck squamous cell cancer that has come back (recurrent) or has occurred after having cancer in the past (second primary). Immunotherapy with bintrafusp alfa may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving bintrafusp alfa and stereotactic body radiation therapy may help to control recurrent head and neck squamous cell cancer.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Head and Neck Squamous Cell Carcinoma, Second Primary Squamous Cell Carcinoma of the Head and Neck
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (bintrafusp alfa, SBRT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bintrafusp Alfa
Other Intervention Name(s)
Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy
Other Intervention Name(s)
SABR, SBRT, Stereotactic Ablative Body Radiation Therapy
Intervention Description
Undergo SBRT
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
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.
Time Frame
From treatment initiation until a recurrence, progression or occurrence or death, whichever comes first, assessed at 1 year
Secondary Outcome Measure Information:
Title
Overall response rate
Description
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.
Time Frame
Up to 3 years
Title
Time to progression
Description
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.
Time Frame
Up to 1 year
Title
Loco-regional failure free survival rate
Description
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.
Time Frame
From treatment initiation until local failure or death from any cause, whichever occurs first, assessed up to 1 year
Title
Distant metastases rate
Description
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.
Time Frame
From treatment initiation until distance metastases or death from any cause, whichever occurs first, assessed up to 1 year
Title
Overall survival rate
Description
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.
Time Frame
From treatment initiation until time to death from any cause, assessed up to 1 year
Title
Incidence of acute and late adverse events
Description
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.
Time Frame
Up to 90 days following the last dose of bintrafusp alfa
Title
Fibrosis-related toxicities
Description
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.
Time Frame
Up to 90 days following the last dose of bintrafusp alfa
Title
Fibrosis-related functional outcomes
Time Frame
Up to 24 months
Title
Patient-reported outcome (PRO) measures of symptoms
Description
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.
Time Frame
Up to 24 months post reirradiation
Title
Volumetric tumor regression rate
Time Frame
Up to 3 years
Title
Magnetic resonance imaging kinetic biomarkers
Time Frame
Up to 24 months
Title
Quality-adjusted-life-years
Description
Will be measured between bintrafusp alfa plus stereotactic body radiation therapy (SBRT) reirradiation and historic SBRT reirradiation control.
Time Frame
Up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Renata Ferrarotto
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33720067
Citation
Saint A, Van Obberghen-Schilling E. The role of the tumor matrix environment in progression of head and neck cancer. Curr Opin Oncol. 2021 May 1;33(3):168-174. doi: 10.1097/CCO.0000000000000730.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center
Learn more about this trial
Bintrafusp Alfa and Stereotactic Body Radiation Therapy for the Treatment of Recurrent or Second Primary Head and Neck Squamous Cell Cancer
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