Phase II Evaluation of Concurrent Ipilimumab Therapy and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Malignant Melanoma
试验速览
- 阶段
- 2 期
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity
研究概览
简要总结
The purpose of this study is to evaluate if precisely-targeted radiation therapy, known as stereotactic ablative radiotherapy (SART), given during treatment with the drug ipilimumab (Yervoy) will improve survival for patients with melanoma that has spread to five or fewer sites (oligometastatic).
Blood samples will be collected for research purposes. Planned studies include exploration of certain gene mutations and serum markers as predictors of response to ipilimumab treatment. Research lab studies will also evaluate if circulating tumor cells (CTC) can be accurately detected and isolated from the blood using novel laboratory techniques and if they are a prognostic/predictive marker for treatment response. Test results will not be given to participants or their physicians. In some cases, CTC may be grown for long-term cell lines for further research.
详细描述
Primary Objectives:
- To evaluate the effectiveness of concurrent ipilimumab therapy and SART of melanoma based on 1-year and 2-year overall survival.
- To evaluate the safety and tolerability of concurrent ipilimumab therapy and SART of melanoma based on CTCAE grading of toxicities, and to identify any novel or unexpected Grade 3 or 4 toxicities thought specifically related to ipilimumab and concurrent SART during first 3 cycles of ipilimumab therapy (prior to week 9) in a Phase II study.
Secondary Objectives:
- To evaluate the 1-year and 2-year disease control rates (CR+PR+SD)
- Assess treatment response based on Immune Related Response Criteria (irRC) and mWHO criteria.
- Characterize overall survival by Kaplan-Meier analysis.
Exploratory 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
- •Stage III or IV melanoma (AJCC 6th edition) with 5 or less metastatic sites that are not amenable to curative surgical resection, but can be adequately delineated for SART
- •All sites of metastatic disease acceptable except brain-only and eye metastases, provided SART can be safely delivered to the site.
- •Up to 2 prior systemic treatments for metastatic disease.
- •Mucosal or ocular melanoma is allowed.
- •Radiotherapy consultation and insurance preapproval for SART prior to enrollment.
- •CT or MRI within 28 days of enrollment showing no evidence of brain metastases. Brain metastases allowed if stable by scans for ≥ 28 days following treatment.
- •CT, PET/CT or MRI scan of chest, abdomen, pelvis (and soft tissue as indicated); bone scan (as indicated); and photographs of skin lesions (if applicable) within 28 days of enrollment.
- •Hematology, liver function and renal function lab tests within required parameters.
- •Recovered from all prior surgery and/or adjuvant treatment.
- •No active or chronic infection with HIV, Hepatitis B or Hepatitis C.
- •ECOG Performance Status 0 or
- •Men and women ≥ 18 years old.
- •Men/Women of childbearing potential must use adequate contraception.
排除标准
- •Untreated or uncontrolled brain metastases.
- •Prior treatment with CTLA-4 agent, PD-1 or PD-1 ligand mAb or inhibitor for metastatic disease or as adjuvant therapy (or participation in blinded study).
- •History of melanoma-associated retinopathy.
- •History of other active malignancy within last 2 years, except adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma in situ of cervix, unless disease-free for 2 years.
- •Autoimmune disease (vitiligo is not a basis for exclusion).
- •History of clinically active diverticulitis (diverticulosis is not exclusion criterion per se).
- •Serious uncontrolled medical disorder or active infection that would impede treatment.
- •Underlying medical or psychiatric condition that would cause administration of ipilimumab to be hazardous, or would obscure interpretation of AEs.
- •Any non-oncology vaccine therapy up to 1 month before or after any dose of ipilimumab.
- •Concomitant therapy with IL-2, interferon, other non-study immunotherapy, or cytotoxic chemotherapy; immune-suppressive agents within 30 days of registration; other investigational therapies; chronic use of systemic corticosteroids (however, a low stable dose steroid for mild brain edema or adrenal insufficiency is allowed; topical and inhaled standard dose corticosteroids are allowed).
- •Dementia or significantly altered mental status that would prohibit understanding or rendering of informed consent and compliance with protocol requirements.
- •Pregnant or breastfeeding women.
- •Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g. infectious) illness.
研究组 & 干预措施
Ipilimumab + SART
Patients with oligometastatic but unresectable malignant melanoma will receive induction ipilimumab plus concurrent SART followed by maintenance ipilimumab.
干预措施: Ipilimumab (Drug)
Ipilimumab + SART
Patients with oligometastatic but unresectable malignant melanoma will receive induction ipilimumab plus concurrent SART followed by maintenance ipilimumab.
干预措施: Stereotactic Ablative Radiosurgery (SART) (Radiation)
结局指标
主要结局
Safety and tolerability of concurrent ipilimumab and SART - Acute Toxicity
时间窗: Week 9
Safety and tolerability of concurrent ipilimumab and SART - Subacute Toxicity
时间窗: Week 15
次要结局
- 1-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria(2 year minimum follow up on study participants)
- 2-year disease control rates (CR+PR+SD) based on irRC and mWHO criteria(2 year minimum follow up on study participants)
- 1-year overall survival(2 year minimum follow up on study participants)
- 2-year overall survival(2 year minimum follow up on study participants)
研究者
Wolfram Samlowski
Physician, Comprehensive Cancer Centers of Nevada; Member, Developmental Therapeutics and Genitourinary Committee, US Oncology Research; Clinical Professor, University of Nevada, Reno
Comprehensive Cancer Centers of Nevada