A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Rate of dose limiting toxicities
研究概览
简要总结
The purpose of this study is to test the safety and tolerability of the research study drugs nivolumab, ipilimumab, lomustine, bevacizumab, and temozolomide when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed high grade glioma.
Additional aims of the study are to:
- Find out side effects (good and bad) of study drug combinations.
- Evaluate any preliminary evidence of anticancer activity of study drug combinations .
- Evaluate tumor characteristics by collecting brain tumor tissue samples.
- Measure the amount of nivolumab and ipilimumab in biospecimens.
- Look at biomarkers in biospecimens.
详细描述
Patients having a clinically planned surgical procedure (biopsy or cytoreduction) for a suspected diagnosis of high grade glioma will be approached for participation in this study. Tumor tissue obtained from surgery will be used for histological diagnosis and clinical molecular profiling, and excess tumor tissue will be collected for potential correlative studies. A small sample of blood and CSF for research will also be collected.
Once a diagnosis of high grade glioma is confirmed, the patient will be allocated to one of the study arms. Treatment will be started approximately 7-42 days following surgery once the patient has recovered from surgery. Routine clinical evaluations will be performed prior to treatment initiation and throughout treatment as clinically indicated. Radiographic brain imaging will be performed approximately 21-42 after treatment initiation and then routinely for medical management. Tumor response will be assessed according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) Working Group criteria.
Treatment may continue until the patient experiences unacceptable toxicity or clear disease progression. The determination of whether to stop treatment due to disease progression will be based on the investigator's evaluation of the patient's clinical and radiographic condition, taking into consideration the interpretation of localized inflammatory responses that can mimic radiographic features of tumor progress. Patients discontinuing treatment will have further medical management as directed by their treating physician.
As part of follow-up, if the patient undergoes a surgery, results of clinical molecular profiling will be collected, and excess resected tumor tissue will be collected if available along with blood and CSF for correlative studies. A record of any additional anti-cancer treatments and survival status will be made every three to six months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Participant has the ability to understand and the willingness to provide a signed and dated informed consent form.
- •Participant has the willingness to comply with all study procedures and availability for the duration of the study.
- •Participant is being evaluated for a potential, or known, diagnosis of high grade glioma.
- •Participant is a candidate for brain surgery or has undergone prior surgery and has not received any additional treatment for high grade glioma.
- •Participant is male or female, ≥ 18 years of age.
- •Participant has a Karnofsky Performance Status (KPS) ≥ 60%:
排除标准
- •Participant has received prior anti-cancer treatment for high grade glioma.
- •Participant has a diagnosis of immunodeficiency or active autoimmune disease.
- •Participant is receiving chronic systemic steroid therapy in dosing exceeding 8 mg daily of dexamethasone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Note: This is assessed after surgery, prior to starting drug treatment.
- •Participant has received a live vaccine within 28 days prior to the first dose of study agent. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), typhoid vaccine, and intranasal influenza vaccines (e.g., FluMist®).
- •Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements).
- •Participant is a female of childbearing potential who is pregnant or nursing.
- •Participant has a history of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months.
- •Participant has a history of intestinal perforations, fistula, hemorrhages, and/or hemoptysis ≤ 6 months prior to first study treatment.
- •Participant has active gastrointestinal bleeding.
- •Participant has uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg).
研究组 & 干预措施
4 Nivo-Ipi-CCNU-TMZ
Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide
干预措施: Lomustine (Drug)
4 Nivo-Ipi-CCNU-TMZ
Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide
干预措施: Ipilimumab (Drug)
4 Nivo-Ipi-CCNU-TMZ
Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide
干预措施: 5-day Temozolomide (Drug)
1 SOC (closed to enrollment)
Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide
干预措施: Temozolomide (Drug)
1 SOC (closed to enrollment)
Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide
干预措施: conformal brain radiation therapy (Radiation)
2 Nivo
Nivolumab
干预措施: Nivolumab monotherapy (Drug)
3 Nivo-Ipi (closed to enrollment)
Nivolumab plus Ipilimumab
干预措施: Nivolumab (Drug)
3 Nivo-Ipi (closed to enrollment)
Nivolumab plus Ipilimumab
干预措施: Ipilimumab (Drug)
4 Nivo-Ipi-CCNU-TMZ
Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide
干预措施: Nivolumab (Drug)
5 Nivo-Ipi-TMZ
Nivolumab plus Ipilimumab plus 5-day Temozolomide
干预措施: Nivolumab (Drug)
5 Nivo-Ipi-TMZ
Nivolumab plus Ipilimumab plus 5-day Temozolomide
干预措施: Ipilimumab (Drug)
5 Nivo-Ipi-TMZ
Nivolumab plus Ipilimumab plus 5-day Temozolomide
干预措施: 5-day Temozolomide (Drug)
6 Nivo-Ipi-Bev-TMZ
Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide
干预措施: Nivolumab (Drug)
6 Nivo-Ipi-Bev-TMZ
Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide
干预措施: Ipilimumab (Drug)
6 Nivo-Ipi-Bev-TMZ
Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide
干预措施: Bevacizumab (Drug)
6 Nivo-Ipi-Bev-TMZ
Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide
干预措施: 5-day Temozolomide (Drug)
结局指标
主要结局
Rate of dose limiting toxicities
时间窗: first 28 days of treatment
treatment-related adverse events that impact administration of treatment
次要结局
- Progression free survival (PFS)(up to 5 years)
- Treatment-related adverse events(approximately 7 months)
- Tumor response rates(up to 5 years)
- Overall survival (OS)(up to 5 years)
- Levels of immunotherapeutic agents in specimens(approximately 4 months)
- Change in clinical molecular profile of tumor tissue after treatment(approximately 6 months to 1 year)
研究者
Santosh Kesari
Professor, Neurosciences
Saint John's Cancer Institute