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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Bintrafusp Alfa (Drug)
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.
干预措施: Quality-of-Life Assessment (Other)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: 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.
次要结局
- To Evaluate Volumetric Tumor Regression Rate and MRI Kinetic Biomarkers After M7824 Plus SBRT(up to 1 year)
- Overall Survival (OS)(Up to 1 year)
- Progression-free Survival (PFS) Rate at 1 Year(Up to 1 year)
- Overall Response by RECIST(Tumor reassessment during treatment)
- To Evaluate Patient Reported Outcome (PRO) Measures of Symptoms Using MD Anderson Symptom Inventory (MDASI)(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)
- To Compare Quality-Adjusted-Life-Years (QALY) Between M7824 Plus SBRT Reirradiation and Historic SBRT Reirradiation Control(up to 1 year)