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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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ClinicalTrials.gov Identifier: NCT04220775
Recruitment Status : Recruiting
First Posted : January 7, 2020
Last Update Posted : May 8, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Description
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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.

Condition or disease Intervention/treatment Phase
Recurrent Head and Neck Squamous Cell Carcinoma Second Primary Squamous Cell Carcinoma of the Head and Neck Drug: Bintrafusp Alfa Other: Quality-of-Life Assessment Other: Questionnaire Administration Radiation: Stereotactic Body Radiation Therapy Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 18, 2020
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.
 Drug: Bintrafusp Alfa
Given IV
Other Names:
  • Anti-PDL1/TGFb Trap MSB0011359C
  • M7824
  • MSB0011359C

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: From treatment initiation until a recurrence, progression or occurrence or death, whichever comes first, assessed at 1 year ]
    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 :
  1. Overall response rate [ Time Frame: Up to 3 years ]
    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.

  2. Time to progression [ Time Frame: Up to 1 year ]
    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.

  3. 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 ]
    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.

  4. Distant metastases rate [ Time Frame: From treatment initiation until distance metastases or death from any cause, whichever occurs first, 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.

  5. 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.

  6. Incidence of acute and late adverse events [ Time Frame: Up to 90 days following the last dose of bintrafusp alfa ]
    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.

  7. Fibrosis-related toxicities [ Time Frame: Up to 90 days following the last dose of bintrafusp alfa ]
    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.

  8. Fibrosis-related functional outcomes [ Time Frame: Up to 24 months ]
  9. Patient-reported outcome (PRO) measures of symptoms [ Time Frame: Up to 24 months post reirradiation ]
    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.

  10. Volumetric tumor regression rate [ Time Frame: Up to 3 years ]
  11. Magnetic resonance imaging kinetic biomarkers [ Time Frame: Up to 24 months ]
  12. Quality-adjusted-life-years [ Time Frame: Up to 24 months ]
    Will be measured between bintrafusp alfa plus stereotactic body radiation therapy (SBRT) reirradiation and historic SBRT reirradiation control.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

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): NCT04220775


Contacts
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Contact: Renata Ferrarotto 713-792-6363 rferrarotto@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Renata Ferrarotto    713-792-6363    rferrarotto@mdanderson.org   
Principal Investigator: Renata Ferrarotto         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Renata Ferrarotto M.D. Anderson Cancer Center
More Information
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Additional Information:

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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04220775    
Other Study ID Numbers: 2019-0608
NCI-2019-07625 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2019-0608 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: January 7, 2020    Key Record Dates
Last Update Posted: May 8, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
 Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Atezolizumab
Antineoplastic Agents