A Phase II Study of High Dose Bolus IL2 in Combination With Low Dose Ipilimumab Followed Sequentially by Nivolumab in Patients With Inoperable Stage III or Stage IV Melanoma Who Have Failed Prior Anti-PD1 Immunotherapy
概览
- 阶段
- 2 期
- 干预措施
- Interleukin-2
- 疾病 / 适应症
- Melanoma Stage III
- 发起方
- H. Lee Moffitt Cancer Center and Research Institute
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Response Rate
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
The purpose of this study is to find out if the administration of Interleukin-2 concurrently with ipilimumab followed by Nivolumab will result in improved anti-cancer activity and if it is effective for advanced melanoma.
详细描述
This is a Phase II study of high dose bolus interleukin-2 (HD IL2) in combination with low dose ipilimumab followed sequentially by nivolumab in patients with advanced inoperable stage III or stage IV melanoma who have failed prior anti-PD1 immunotherapy. The planned treatment consists of up to 3 courses (One cycle is 21 days and one course is 4 cycles). HD IL2 will be given during week 1 of the 2 initial cycles or each course. Ipilimumab will be given concurrently at the low dose of 1 mg/kg on Day 1 of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on Day 1 of the 3rd cycle of each course. No systemic treatment will be administered during the 4th cycle. Response assessment will occur at the end of the 4th cycle. Patients without evidence of disease progression (RECIST v.1.1) or limiting toxicities will be offered additional courses of treatment for up to a maximum of 3 courses, total
研究者
入排标准
入选标准
- •Histologically or cytologically confirmed metastatic melanoma. This includes American Joint Committee on Cancer (AJCC) stage IV or advanced/inoperable stage III. This also includes patients with a history of lower stage melanoma and subsequent recurrent metastatic disease that is either locally/regionally advanced/inoperable disease or distant metastases
- •Measurable disease, according to RECIST version 1.1
- •Must be free of active brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to enrollment. If known to have prior brain metastases, these must have been adequately managed with standard of care radiation therapy, stereotactic radiosurgery or surgery prior to registration on the study.
- •Must have previously received anti-PD1 immunotherapy (nivolumab or pembrolizumab) and later experienced disease progression.
- •Must not have received systemic therapy or radiotherapy (including SRS) within the preceding 3 weeks. Patients must have recovered from adverse events from previous therapy by the time registration.
- •Must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery, and must be free of significant detectable infection prior to registration.
- •Patients who have received prior anti-CTLA4 monoclonal antibody therapy (ipilimumab or tremelimumab) are eligible.
- •Patients who have previously experienced prior high-grade (grade 3 or 4 by CTCAE criteria) immune related adverse events with immune checkpoint inhibitors must be discussed with the study PI and cleared prior to enrollment on this study in order to ensure patient safety.
- •Patients with BRAF V600 mutant melanoma must have previously received BRAF targeted therapy for metastatic melanoma and later experienced disease progression. Patients who refuse or decline to receive BRAF targeted therapy or were intolerant of BRAF targeted therapy are eligible.
- •Life expectancy of greater than 3 months in the opinion of the investigator
排除标准
- •Patients who have had systemic therapy for melanoma or radiotherapy within 3 weeks prior to registering on the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. Patients with a history of endocrinopathies (e.g. hypothyroidism) are eligible if they are stable on hormone replacement therapy. Patients with a history of adrenal insufficiency are not eligible.
- •Patients may not be receiving any other investigational agents.
- •Patients with active brain metastasis are excluded
- •Patients with clinically significant cardiovascular or cerebrovascular disease
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients who have other current malignancies are not eligible. Patients with other malignancies are eligible if they have been continuously disease free for \> 2 years prior to the time of registration. Patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ are eligible. Patients with prior history of basal or squamous skin cancer are eligible. Patients who have had multiple primary melanomas are eligible.
- •Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids or steroid inhalers. If a patient had been taking steroids, at least 2 weeks must have passed since the last dose.
研究组 & 干预措施
Treatment
HD IL2 (600,000 units/kg/dose IV) will be given during week 1 of the 2 initial cycles or each course. Ipilimumab will be given concurrently at the low dose of 1 mg/kg during week one of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on during week one of the 3rd cycle of each course. No systemic treatment will be administered during the 4th cycle. Patients without evidence of disease progression (RECIST v.1.1) or limiting toxicities will be offered additional courses of treatment for up to a maximum of 3 courses, total.
干预措施: Interleukin-2
Treatment
HD IL2 (600,000 units/kg/dose IV) will be given during week 1 of the 2 initial cycles or each course. Ipilimumab will be given concurrently at the low dose of 1 mg/kg during week one of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on during week one of the 3rd cycle of each course. No systemic treatment will be administered during the 4th cycle. Patients without evidence of disease progression (RECIST v.1.1) or limiting toxicities will be offered additional courses of treatment for up to a maximum of 3 courses, total.
干预措施: Ipilimumab
Treatment
HD IL2 (600,000 units/kg/dose IV) will be given during week 1 of the 2 initial cycles or each course. Ipilimumab will be given concurrently at the low dose of 1 mg/kg during week one of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on during week one of the 3rd cycle of each course. No systemic treatment will be administered during the 4th cycle. Patients without evidence of disease progression (RECIST v.1.1) or limiting toxicities will be offered additional courses of treatment for up to a maximum of 3 courses, total.
干预措施: Nivolumab
结局指标
主要结局
Response Rate
时间窗: Up to 9 months
Response rate (Complete Response + Partial Response) of HD IL2 plus low dose ipilimumab followed sequentially by nivolumab in patients with inoperable stage III or stage IV melanoma who have either failed prior treatment with anti-PD1 immunotherapy (nivolumab or pembrolizumab) or have demonstrated tumor progression following such therapy.
次要结局
- Progression Free Survival(Up to 5 years)
- Overall Survival(Up to 5 years)