Phase 2 Study (With Safety Lead in) of the Safety, Tolerability and Efficacy of Anti-CTLA4 (Ipilimumab) and Anti-PD-1 (Nivolumab) in Combination With Radiation Therapy to 50-66 Gy in Low-Intermediate Volume, Local-Regionally Advanced HPV-Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Radiographic (RECIST) Response
研究概览
简要总结
This phase II trial studies the side effects and best dose of ipilimumab, nivolumab, and radiation therapy and how well they work in treating patients with advanced human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving ipilimumab, nivolumab, and radiation therapy may work better in treating patients with HPV positive oropharyngeal squamous cell carcinoma.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety, tolerability and feasibility of ipilimumab and nivolumab when administered concurrently with reduced-field radiotherapy (intensity-modulated radiation therapy [IMRT]).
II. To evaluate the clinical complete response rate to ipilimumab, nivolumab and IMRT with reduced field at six months as indicated by fluorodeoxyglucose - positron emission tomography/computed tomography (FDG-PET/CT) post completion of radiation therapy (RT).
III. To evaluate the 2-year progression-free survival (PFS) rate of subjects with low-intermediate volume, local-regionally advanced, human papilloma virus (HPV)-positive squamous cell carcinoma of the head and neck (SCCHN) treated with ipilimumab, nivolumab and reduced-field IMRT.
SECONDARY OBJECTIVES:
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
- •Histologically or cytologically newly confirmed diagnosis of squamous cell carcinoma (including the histological variants of papillary or basaloid) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls)
- •Clinical American Joint Committee on Cancer (AJCC) 7th edition stage T1N2a-N2CM0, T2N1-N2CM0, T3N0-N2CM0, equivalent to AJCC 8th edition stage 1 and 2 (T1 N2, T2 N1-N2, T3 N0-N2) excluding T1N0-N1 and T2N0 (Brian O'Sullivan et al. 2016)
- •Tumor positive for p16 immunohistochemistry (IHC) (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells) and HPV DNA in situ hybridization or HPV messenger ribonucleic acid (mRNA) RNAScope. Repeat samples may be required if adequate diagnostic tissue is unavailable for testing
- •Zubrod Performance Status of 0-1
- •Patients must have radiographically evident measurable disease at the primary site or at nodal stations per response evaluation criteria in solid tumors (Response Evaluation Criteria in Solid Tumors [RECIST]) 1.1 documented by diagnostic quality CT or magnetic resonance imaging (MRI) of the neck with contrast within 28 days prior to registration; a FDG-PET/CT of the neck performed for the purposes of radiation planning is acceptable as a substitute if the CT is of diagnostic quality
- •Diagnostic quality cross sectional imaging of the thorax within 28 days prior to registration. A 18-FDG-PET/CT or conventional CT are acceptable
- •FDG-PET/CT of the neck is required within 28 days prior to registration for comparison to post treatment FDG-PET/CT. Note: Repeat imaging for variability within 96 hours of this time frame should be allowed to avoid unnecessary re-imaging and its financial and potential physical consequences for patients
- •History and physical exam within 1 month prior to registration
- •Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) by radiation oncologist, medical oncologist or ear, nose, throat (ENT)/head and neck surgeons within 28 days prior to registration
- •Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 2 weeks prior to registration)
- •Platelets >= 100,000 cells/mm^3 (within 2 weeks prior to registration)
- •Hemoglobin >= 8.0 g/dl (within 2 weeks prior to registration); Note: The use of transfusion or other intervention to achieve Hgb >= 8.0 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 (within 2 weeks prior to registration)
- •Bilirubin < 2 mg/dl (within 2 weeks prior to registration)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the upper limit of normal (within 2 weeks prior to registration)
- •Sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), albumin, amylase, lipase, thyroid stimulating hormone (TSH) within 2 weeks prior to registration
- •Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential
- •Seronegative for active hepatitis-B or hepatitis-C infection and seronegative for human immunodeficiency virus (HIV)
- •Mandatory submission of hematoxylin and eosin (H&E) and paraffin-embedded tumor block or unstained slides
排除标准
- •Cancers of the oral cavity (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive
- •Carcinoma of the neck of unknown primary site origin (even if p16 positive)
- •Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles
- •Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease
- •Simultaneous primary cancers or separate bilateral primary tumor sites
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
- •Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable; patients who have received PD-1/PD-L1 or CTLA4 therapy for a previous malignancy are not eligible
- •Prior RT to the region of the study cancer that would result in overlap of radiation therapy fields
- •Severe, active co-morbidity defined as any of the following: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration; hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; a diagnosis of immunodeficiency or use of any form of systemic immunosuppressive therapy. The use of physiologic doses of corticosteroids may be approved after consultation with the sponsor
- •Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Steroid premedications for contrast allergy allowed
- •Has evidence of active, non-infectious pneumonitis
- •Has received a live vaccine within 30 days of planned start of study therapy
- •Pregnancy or breast-feeding; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
- •History of severe hypersensitivity or contraindication to CT or PET contrast material uncontrolled with pre-medications (steroids, antihistamines)
研究组 & 干预措施
Treatment (nivolumab, ipilimumab, IMRT)
Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Treatment (nivolumab, ipilimumab, IMRT)
Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Treatment (nivolumab, ipilimumab, IMRT)
Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab (Biological)
Treatment (nivolumab, ipilimumab, IMRT)
Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Ipilimumab (Biological)
Treatment (nivolumab, ipilimumab, IMRT)
Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
结局指标
主要结局
Radiographic (RECIST) Response
时间窗: 6 months post completion of radiation therapy (approximately 9 months post start of treatment)
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter with an absolute increase of at least 5 mm or the appearance of new lesions
Pathologic Response -- Percent Viable Tumor Change
时间窗: From first registration on trial (baseline biopsy) to post Cycle 1 of IO (6 weeks after start of treatment)
Pathologic response refers to the evaluation of how much a tumor has shrunk after treatment by the pathologist on trial examining tissue samples under a microscope. Tissue samples from baseline and at follow up were evaluated for tumor response. Percent viable tumor change is calculated using viable tumor data collected at the biopsy to the biopsy at the end of Cycle 1 of treatment.
次要结局
- Toxicity (Number of Adverse Events)(time of first drug administration to 30 days after last drug administration)
- Survival Analysis -- Progression Free Survival(12 month post treatment follow up (15 months post treatment start), 18 month post treatment follow up (21 months post treatment start), 24 month post treatment follow up (27 months post treatment start))
- Survival Analysis -- Overall Survival (Percentage of Participants Alive at 12 Months, 18 Months, and 24 Months)(12 month post treatment follow up (15 months post treatment start), 18 month post treatment follow up (21 months post treatment start), 24 month post treatment follow up (27 months post treatment start))