Bintrafusp Alfa and Stereotactic Body Radiation Therapy for the Treatment of Recurrent or Second Primary Head and Neck Squamous Cell Cancer

Phase 1

Terminated

Conditions: Recurrent Head and Neck Squamous Cell Carcinoma
Second Primary Squamous Cell Carcinoma of the Head and Neck

Interventions: Drug: Bintrafusp Alfa
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Radiation: Stereotactic Body Radiation Therapy

Registration Number: NCT04220775

Lead Sponsor: M.D. Anderson Cancer Center

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (bintrafusp alfa, SBRT)	Quality-of-Life Assessment	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.
Treatment (bintrafusp alfa, SBRT)	Questionnaire Administration	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.
Treatment (bintrafusp alfa, SBRT)	Stereotactic Body Radiation Therapy	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.
Treatment (bintrafusp alfa, SBRT)	Bintrafusp Alfa	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.

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity (DLT)	The DLT window is from first M7824 dose (D0) until 14 days post SBRT (D28).	For the phase I part of this phase I/II study, the primary endpoint was DLT defined as any grade 3 or above AE resulting in inability to complete radiotherapy due to toxicity related to M7824 or the combination of M7824 and SBRT.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 1 year	OS was defined was from treatment start to death or to the last follow-up
Progression-free Survival (PFS) Rate at 1 Year	Up to 1 year	For the phase II part of this phase I/II study, the primary endpoint was to evaluate progression-free survival (PFS) at 1 year. Progression-free survival was defined as from treatment start to progression, or death, whichever occurred first, or to the last follow-up.
Overall Response by RECIST	Tumor reassessment during treatment	Best overall response by RECIST 1.1
To Evaluate Patient Reported Outcome (PRO) Measures of Symptoms Using MD Anderson Symptom Inventory (MDASI)	up to 1 year
To Evaluate Volumetric Tumor Regression Rate and MRI Kinetic Biomarkers After M7824 Plus SBRT	up to 1 year
To Evaluate Fibrosis-related Toxicities and Functional Outcomes	up to 1 year
To Evaluate Acute and Late Toxicity Using Common Terminology Criteria for Adverse Events (CTCAE)-v5.0	Up to 1 year	Common Terminology Criteria for Adverse Events (CTCAE)-v5.0
To Compare Quality-Adjusted-Life-Years (QALY) Between M7824 Plus SBRT Reirradiation and Historic SBRT Reirradiation Control	up to 1 year