An Open-Label, Phase 2 Study of NEO100 in Participants With Residual, Progressive or Recurrent High-Grade Meningioma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Progression free survival as six months (PFS6).
研究概览
简要总结
This multi-site, Phase 2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO100 (perillyl alcohol) for the treatment of patients with residual high-grade meningioma following resection surgery, radiographically-confirmed progression of high-grade meningioma or recurrent high-grade meningioma. There will be up to 30 patients enrolled in this study to have 29 evaluable patients. NEO100 will be self-administered four times daily on a 28-day treatment cycle until disease progression, death or patient withdraw from study for any reason, whichever occurs first.
详细描述
Meningiomas are the most common primary brain tumor with an incidence rate of 8.33 per 100,000. They originate from the meningeal (dural) coverings of the brain and spinal cord. Although the majority of meningiomas are benign, these tumors can grow slowly until they are very large, if left undiscovered, and, in some locations can be severely disabling and/or life-threatening.
There is a relative paucity of prospective clinical trials that provide an evidenced-based agreed upon approach to managing meningioma. Furthermore, uniformly applied guidelines have been difficult to achieve given the typical pattern of slow growth.
Meningiomas can be organized into two groups. WHO Grade I meningioma are histologically benign and can be managed by careful observation as recommended in the National Comprehensive Cancer Network Guidelines. Grade I meningiomas are low grade and have a 7-20% recurrence risk. For most other patients (WHO Grade II and WHO Grade III) there is an increased risk of recurrence and death. Grade II meningiomas occur in 5-15% of cases with a 30-40% recurrence risk and Grade III meningiomas occur 1-3% of the time with a 50-80% recurrence risk. For Grade I and Grade II meningiomas, gross total resection is standard. WHO Grade II and WHO Grade III meningiomas are referred to as high-grade meningiomas.
Questions remain regarding the selection and timing of treatment, especially in cases of recurrent meningioma or newly diagnosed high-grade meningioma (WHO Grade II or Grade III meningioma). For patients undergoing definitive therapy, complete resection (gross total resection) has been the standard. However, there is a significant subset of patients who are not successfully managed by surgery alone, or in whom a complete resection is not possible due to the relationship of the tumor to important anatomy. Complete tumor resection is not always achievable as many meningiomas arise at or near critical neural or vascular structures or in sites with limited surgical access When a gross total resection cannot be accomplished, post-operative radiation therapy is often considered (e.g., single-session stereotactic radiosurgery, hypofractionated stereotactic radiation therapy and conventionally fractionated external beam radiation therapy).
The potential for recurrence, whether following subtotal resection or gross-total resection, is well recognized. As a result, there is increasing evidence from retrospective review of case histories in support of radiation therapy as primary therapy for high-grade meningioma (or radiation prior to or following resection surgery). The relative efficacy of these approaches has not yet been tested in rigorously designed prospective clinical trials.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must:
- •Have histologically confirmed WHO Grade II or III meningioma that is residual, progressive or recurrent following at least minimally safe resection and radiation therapy. Metastatic meningiomas are allowed.
- •Residual disease is defined as residual measurable disease (without a requirement for progression). Residual measurable disease is defined by bidimensionally measurable lesions with clearly defined margins by MRI scan(s) with a minimum diameter of 10mm in both dimensions.
- •Progressive disease is defined as an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area). The change must occur between scans separated by no more than 24 months.
- •Recurrent disease is defined as new evidence of measurable disease following complete resection (10mm in both dimensions).
- •Be on a stable or decreasing dose of steroids for at least five days prior to the date of informed consent.
- •Participants must have failed maximal safe resection and radiation therapy.
- •There is no limit on the number of prior surgeries, radiation therapy, radiosurgery treatments or systemically administered therapeutic agents, however, these treatment(s) must comply with the following:
- •There is no limit on the number of prior therapies.
- •Prior medical therapy is allowed but is not required.
- •No chemotherapy, other investigational agents within 14 days of study treatment.
- •For prior systemic agents, participants must be at least 4 weeks (or 5 half-lives, whichever is shorter) from other prior cytotoxic chemotherapy (6 weeks from nitrosoureas/alkylating agents) or biologic therapies.
- •No other concurrent receipt of investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study.
- •Patients may have been treated with standard external beam radiation or radiosurgery in any combination; however an interval of ≥12 weeks (84 days) must have elapsed from the completion of the radiation therapy to the initiation of study therapy unless there is histopathologic confirmation of recurrent tumor or there is new enhancing tumor outside the radiation field (beyond the high dose region or the 80% isodose line). In addition, there must be subsequent evidence of tumor progression after completion of radiation therapy;
- •An interval of ≥ 28 days and full recovery (no ongoing safety issues) from surgical resection is required;
- •Meningiomas that have resulted from prior radiation therapy are allowed.
- •There must be an interval of ≥ 7 days from stereotactic biopsy; and
- •Participants must have recovered to grade ≤1 or pretreatment baseline from clinically significant adverse events related to prior therapy (exclusions include, but are not limited to alopecia, laboratory values listed per inclusion criteria and lymphopenia)
- •Patient must be ≥ 12 years of age.
- •Patient must have an ECOG performance status of 0-2 or KPS ≥
- •Patient must have an expected survival of at least three months.
- •Patient must be willing to provide blood sample for pharmacokinetic study (to assess proper administration of NEO100).
- •Patient must have adequate organ and marrow function as defined below:
- •White blood cell (WBC) ≥2000/microliter
- •Absolute neutrophil count (ANC) ≥ 1,500/microliter
- •Platelets ≥ 100,000/microliter
- •Hemoglobin ≥9 gm/dl
- •AST (SGOT)/ALT (SPGT) ≤ 2.5 × laboratory upper limit of normal (ULN)
- •Serum creatinine ≤ 1.5 x laboratory upper limit of normal (ULN) or
- •Creatinine clearance (meas or calc) ≥60mL/min for participants with creatinine levels >1.5x laboratory upper limit of normal (ULN)
- •Total serum bilirubin ≤ 1.5 x laboratory upper limit of normal (ULN) except participants with Gilbert's Syndrome who can have a total serum bilirubin of <5 x laboratory upper limit of normal (ULN)
- •MRI (or CT if MRI contraindicated) within 14 days prior to start of study drug. Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. If steroids are added or the steroid dose is increased between the date of the screening scan and the start of treatment, a new baseline scan is required.
- •Female patients of child-bearing potential and male patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30 days prior to the first administration of study drug, for the duration of study participation, and for 90 days following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- •A female of child-bearing potential is any woman (regardless of sexual orientation, not having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- •Has not undergone a hysterectomy or bilateral oophorectomy; or
- •Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- •A negative serum pregnancy test will be required of all female patients of child-bearing potential within seven days prior to initiating study drug.
- •A serum pregnancy test will be repeated immediately if pregnancy is suspected.
- •Women must not be breastfeeding.
- •Patient must have the ability to understand, and the willingness comply with scheduled visits, treatment schedule, laboratory testing and other requirements of the study as confirmed by signing a written informed consent document.
排除标准
- •Patients who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days (or 5 half-lives, whichever is shorter) of study treatment.
- •Patient has completed chemo-radiation within the last 84 days prior to the first administration of study drug, unless new contrast enhancement is outside of radiation field, or there is tissue proven recurrence or progression.
- •Patient has had surgery within seven days prior to the date of informed consent.
- •Patient has had cytotoxic chemotherapy within 4 weeks (or 5 half-lives, whichever is shorter), nitrosoureas/alkylating agents within 6 weeks or biologic therapies.
- •Prior treatment with interstitial brachytherapy within 6 months of start of study therapy.
- •Current or planned participation in a clinical trial of an investigational agent or using an investigational medical device.
- •The patient's disease is primarily localized to the brainstem or spinal cord;
- •Patient has not recovered from adverse events due to chemotherapy, immunotherapy, or radiation therapy.
- •Patient has had prior treatment with perillyl alcohol.
- •Patient has a history of allergic reactions attributed to perillyl alcohol.
- •Patient has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patient must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- •Patient has a history of new diagnosis or treatment of cancer other than high-grade meningioma within five years prior to the date of informed consent, except for basal cell carcinoma or squamous cell carcinoma of the skin.
- •Leptomeningeal involvement of the patient's tumor.
研究组 & 干预措施
Patients with high-grade meningioma
30 patients with residual high-grade meningioma following resection surgery, radiographically-confirmed progression of high-grade meningioma or recurrent high-grade meningioma
干预措施: NEO100 (Drug)
结局指标
主要结局
Progression free survival as six months (PFS6).
时间窗: 6 months
Progression free survival
次要结局
- Perillic acid measurement(30 days)
- Objective Tumor response to NEO100 as determined by RANO criteria(6 months)
- Overall survival(12 months)