Phase I/II Trial of Ipilimumab (Immunotherapy) and Hypofractionated Stereotactic Radiation Therapy in Patients With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 143
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of ipilimumab and stereotactic body radiation therapy (SBRT). The safety and effectiveness of these treatments given consecutively will also be studied.
This is an investigational study. SBRT is FDA approved for the control of metastatic and primary tumors. Ipilimumab is FDA approved and commercially available for the treatment of metastatic melanoma that cannot be removed with surgery. The use of SBRT with ipilimumab is investigational. The study doctor can explain how the study drug is designed to work.
Up to 120 participants will be enrolled in this study. All will take part at MD Anderson.
详细描述
Study Groups:
Participants on this study are enrolled into Phase 1 (Dose De-Escalation, or Dose-Finding) or Phase 2 (Dose Expansion), based on when they join the study.
Phase 1: Dose De-Escalation:
If you are found to be eligible to take part in this study, you will be assigned to 1 of 5 groups based on the type of disease you have.
- If you are in Groups 1 or 3, you will receive SBRT and 1 dose of ipilimumab within a few days after your SBRT treatment, and then you will receive 3 more doses of ipilimumab.
- If you are in Groups 2, 4, or 5, you will receive 2 doses of ipilimumab, SBRT, and then 2 more doses of ipilimumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 must have histological confirmation of metastatic cancer with at least one metastatic or primary lesion in the liver, lung, or adrenal gland.
- •Patients who have completed previous systemic therapies 5 drug half-lives or 4-weeks prior to enrollment on study, whichever is shorter. Note: patients with anaplastic thyroid will be waived from this inclusion criteria given the rapid trajectory of their disease.
- •All patients must have at least one metastatic or primary lesion within the lung or liver located in an anatomical location amenable to SBRT treatment with 50 Gy in 4 fractions, or if not, with either a lung, liver, or adrenal lesion treatable to 60 Gy in 10 fractions.
- •Repeat radiation in fields previously radiated will be allowed at the discretion of the treating physician.
- •Age >/= 18 years
- •ECOG performance status </=2 (Karnofsky >60%).
- •Patients must have normal organ and marrow function as defined below: * Total bilirubin </= 2.0 mg/dL. (Does NOT apply to patients with Gilbert's Syndrome) * Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Alanine Aminotransferase (ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) <2.5 X institutional upper limit of normal (patients with liver involvement will be allowed </= 5.0 X institutional upper normal limit) *WBC >/= 2500/uL, ANC >/= 1000/uL *Platelets >/= 75K *Hemoglobin >/= 9g/dL *Creatinine </= 2.0 x ULN
- •Patients must be willing and able to review, understand, and provide written consent before starting therapy.
- •Patients with brain metastasis will be included as long as they are free of neurologic symptoms related to metastatic brain lesions and who do not require or receive systemic corticosteroid therapy in the 14 days prior to beginning ipilimumab therapy
- •Patients that have previously progressed on immunotherapy such as ipilimumab will be eligible.
排除标准
- •Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study.
- •Active diverticulitis, intra-abdominal abscess, Gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
- •Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of Adverse Events: (AE's) e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Known active HIV, Hepatitis B, or Hepatitis C that has not been documented to be cured.
- •Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).
- •Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids while receiving ipilimumab (as long as steroid replacement is significantly greater than what is required for physiologic replacement, i.e. in hypothyroidism).
- •Pregnant women are excluded from this study. Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Acceptable forms of birth control include: Birth control pills plus a barrier method, such as a condom or diaphragm, Intrauterine devices (IUD) plus a barrier method, Implantable or injectable birth control (such as NorplantR or epo-ProveraR) started at least 3 months before joining the study, plus a barrier method, or Double-barrier method, such as a condom when used in combination with a diaphragm. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician.
- •History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.
- •Prior allogeneic stem cell transplantation
研究组 & 干预措施
Group 1 Liver: Concurrent (early) Ipilimumab and SBRT
Participants with at least 1 liver metastasis - Treatment Group 1: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 1 - 4 of Cycle 1.
干预措施: Ipilimumab (Drug)
Group 1 Liver: Concurrent (early) Ipilimumab and SBRT
Participants with at least 1 liver metastasis - Treatment Group 1: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 1 - 4 of Cycle 1.
干预措施: Stereotactic Body Radiation Therapy (SBRT) (Radiation)
Group 2 Liver: Sequential (late) Ipilimumab and SBRT
Participants with at least 1 liver metastasis - Treatment Group 2: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 29 - 33 of each 21 day cycle.
干预措施: Ipilimumab (Drug)
Group 2 Liver: Sequential (late) Ipilimumab and SBRT
Participants with at least 1 liver metastasis - Treatment Group 2: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 liver lesion(s) on Days 29 - 33 of each 21 day cycle.
干预措施: Stereotactic Body Radiation Therapy (SBRT) (Radiation)
Group 3 Lung: Concurrent (early) Ipilimumab and SBRT
Participants with at least 1 lung metastasis - Treatment Group 3: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 1 - 4 of Cycle 1.
干预措施: Ipilimumab (Drug)
Group 3 Lung: Concurrent (early) Ipilimumab and SBRT
Participants with at least 1 lung metastasis - Treatment Group 3: Ipilimumab 3 mg/kg by vein on Day 1 of all 21 day cycles for a total of 4 doses. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 1 - 4 of Cycle 1.
干预措施: Stereotactic Body Radiation Therapy (SBRT) (Radiation)
Group 4 Lung: Sequential (late) Ipilimumab and SBRT
Participants with at least 1 lung metastasis - Treatment Group 4: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 29 - 33 of each 21 day cycle.
干预措施: Ipilimumab (Drug)
Group 4 Lung: Sequential (late) Ipilimumab and SBRT
Participants with at least 1 lung metastasis - Treatment Group 4: Ipilimumab 3 mg/kg by vein on Day 1 of Cycles 1 and 2. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 3 and 4. Each cycle is 21 days. SBRT 50 Gy in 4 fractions to 1 - 4 lung lesion(s) on Days 29 - 33 of each 21 day cycle.
干预措施: Stereotactic Body Radiation Therapy (SBRT) (Radiation)
Group 5 Liver/Lung Metastasis: (late) Ipilimumab and SBRT
Participants with 1 liver or lung metastasis - Treatment Group 5: Ipilimumab 3 mg/kg by vein on Day 1 of Cycle 1. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 2 - 4. Each cycle is 21 days. SBRT 60 Gy in 10 fractions to 1 - 4 lung, liver, or adrenal lesion (s) on Days 1 - 5 and Days 9 - 12 of Cycle 1.
干预措施: Ipilimumab (Drug)
Group 5 Liver/Lung Metastasis: (late) Ipilimumab and SBRT
Participants with 1 liver or lung metastasis - Treatment Group 5: Ipilimumab 3 mg/kg by vein on Day 1 of Cycle 1. After SBRT treatment, Ipilimumab given on Day 1 of Cycles 2 - 4. Each cycle is 21 days. SBRT 60 Gy in 10 fractions to 1 - 4 lung, liver, or adrenal lesion (s) on Days 1 - 5 and Days 9 - 12 of Cycle 1.
干预措施: Stereotactic Body Radiation Therapy (SBRT) (Radiation)
Thyroid Expansion Cohort
Participants enrolled in this arm treated to a total dose of 50 Gy in 4 fractions, 60 Gy in 10 fractions, or 20 Gy in 5 fractions with stereotactic radiotherapy to a liver or lung lesion. The choice of radiation dose will be at the discretion of the treating radiation oncologist.
Participants receive Ipilimumab every 21 days for a total of 4 doses.
干预措施: Ipilimumab (Drug)
Thyroid Expansion Cohort
Participants enrolled in this arm treated to a total dose of 50 Gy in 4 fractions, 60 Gy in 10 fractions, or 20 Gy in 5 fractions with stereotactic radiotherapy to a liver or lung lesion. The choice of radiation dose will be at the discretion of the treating radiation oncologist.
Participants receive Ipilimumab every 21 days for a total of 4 doses.
干预措施: Stereotactic Body Radiation Therapy (SBRT) (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)
时间窗: Third week of second, 21 day cycle
MTD defined as highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort. All enrolled participants will be considered in the DLT analysis. If at any time more than or equal to one third (33%) of participants at a dose level experience DLT, the MTD will be reassessed and the next lowest dose level for the combination therapy considered the MTD.
次要结局
- Response Rate of Ipilimumab and Stereotactic Body Radiation Therapy (SBRT)(30 days after last dose of Ipilimumab)