Clinical Trials /

M7824 Plus Re-irradiation With Stereotactic Body Radiation Therapy for the Curative Intent Treatment of Recurrent Head and Neck Cancer

NCT04220775

Description:

This phase I/II trial studies the side effects and how well bintrafusp alfa (M7824) and stereotactic body radiation therapy (SBRT) work in treating patients with head and neck squamous cell cancer that has come back (recurrent) or has occurred in a region that has been previously radiated . 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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2019-0608
  • SECONDARY ID: NCI-2019-07625
  • SECONDARY ID: 2019-0608
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04220775

Conditions

  • Recurrent Head and Neck Squamous Cell Carcinoma
  • Second Primary Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
Bintrafusp AlfaAnti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359CTreatment (bintrafusp alfa, SBRT)

Purpose

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 OBJECTIVES:

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (bintrafusp alfa, SBRT)ExperimentalPatients 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.
  • Bintrafusp Alfa

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 cancer 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From treatment initiation until a recurrence, progression or occurrence or death, whichever comes first, assessed at 1 year
Safety Issue:
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.

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 3 years
Safety Issue:
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.
Measure:Time to progression
Time Frame:Up to 1 year
Safety Issue:
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.
Measure: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
Safety Issue:
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.
Measure:Distant metastases rate
Time Frame:From treatment initiation until distance metastases or death from any cause, whichever occurs first, assessed up to 1 year
Safety Issue:
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.
Measure:Overall survival rate
Time Frame:From treatment initiation until time to death from any cause, assessed up to 1 year
Safety Issue:
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.
Measure:Incidence of acute and late adverse events
Time Frame:Up to 90 days following the last dose of bintrafusp alfa
Safety Issue:
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.
Measure:Fibrosis-related toxicities
Time Frame:Up to 90 days following the last dose of bintrafusp alfa
Safety Issue:
Description:Will be assessed by the chi-square test or the Fisher's exact test will be applied to evaluate the association between two categorical variables.
Measure:Fibrosis-related functional outcomes
Time Frame:Up to 24 months
Safety Issue:
Description:Will be assessed by the chi-square test or the Fisher's exact test will be applied to evaluate the association between two categorical variables.
Measure:Patient-reported outcome (PRO) measures of symptoms
Time Frame:Up to 24 months post reirradiation
Safety Issue:
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.
Measure:Volumetric tumor regression rate
Time Frame:Up to 3 years
Safety Issue:
Description:To assess after M7824 plus SBRT
Measure:Magnetic resonance imaging kinetic biomarkers
Time Frame:Up to 24 months
Safety Issue:
Description:To assess after M7824 plus SBRT
Measure:Quality-adjusted-life-years comparison
Time Frame:Up to 24 months
Safety Issue:
Description:Will be measured between bintrafusp alfa plus stereotactic body radiation therapy (SBRT) reirradiation and historic SBRT reirradiation control.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

January 4, 2020