A Phase II Randomized Trial of Intralesional Talimogene Laherparepvec (TALIMOGENE LAHERPAREPVEC) With or Without Radiotherapy for Cutaneous Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 3
- 主要终点
- Best Response
研究概览
简要总结
The purpose of this phase II clinical study is to test the good and bad effects of T-VEC (talimogene laherparepvec) with or without hypofractionated radiotherapy on people with melanoma, Merkel cell carcinoma, or other solid tumors with skin metastasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Man or woman ≥ 18 years old
- •Life expectancy > 4 months
- •Histopathologically confirmed melanoma, Merkel cell carcinoma or other solid tumor malignancy
- •Cutaneous subcutaneous soft tissue, or superficial lymphatic metastasis not suitable for surgical resection
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Cutaneous subcutaneous soft tissue, or superficial lymphatic metastasis that is amenable to injection and irradiation and > 10 mm in longest dimension
- •° Cutaneous metastasis in a region of previous radiation therapy is amenable to radiation therapy as part of this protocol if at least 6 months has elapsed since prior radiotherapy and the dose of radiotherapy previously administered did not exceed an equivalent dose of 60 Gy in 2 Gy equivalent fractions at the skin surface (using linear-quadratic modeling with alpha/beta=11.5)
- •Metastasis that is > 10 mm in longest dimensionor exhibits radiotracer uptake consistent with metastasis on PET/CT
- •Adequate coagulation function (platelet count >50 k/mcL, international normalized ratio of < 1.5)
- •Resolution or stabilization of clinically significant adverse events from prior therapy
- •Able to provide valid written informed consent
排除标准
- •Active herpetic skin lesions or prior complications of HSV-1 infection (such as herpetic keratitis, herpetic encephalitis)
- •Receipt of a therapeutic anticoagulant
- •Receipt of live vaccine within 28 days of planned first dose of TVEC
- •Receipt of another cancer therapy (targeted therapy, chemotherapy, investigational therapy, immunotherapy, radiotherapy or surgery) which is yielding an overall response (by response criteria in this study)
- •° Patients with stable or progressing disease (as determined by at least 2 consecutive assessments at 6-week interval) can continue to receive the same therapy during treatment as part of this protocol
- •History of symptomatic autoimmune disease (such as lupus, scleroderma, Crohn's disease, ulcerative colitis) requiring systemic treatment (for example corticosteroids or immunosuppressants); replacement therapy (for example, thyroxine, insulin) is not considered a systemic treatment
- •History of high grade (CTCAE ≥ Grade 3) immune mediated adverse event from prior cancer immunotherapy
- •History of CTCAE ≥ Grade 2 immune mediated endocrinopathy from prior cancer immunotherapy
- •Intermittent or chronic use of oral or intravenous antiherpetic drug (such as acyclovir)
- •Active or chronic hepatitis B or C infection
- •° Previously infected, with evidence of immunity and no evidence of active hepatitis is not an exclusion criterion
- •Known human immunodeficiency virus (HIV) infection
- •Known leukemia or lymphoma
- •Common variable immunodeficiency
- •Patients requiring chronic high dose immunosuppressants including steroids (prednisone daily equivalent of ≥ 10 mg)
- •Known severe congenital or acquired cellular or humoral immunodeficient or immunocompromised patients
- •High likelihood of protocol non-compliance (in opinion of investigator)
- •Woman of childbearing potential unwilling to use effective contraception during protocol treatment and for 3 months after last dose of Talimogene Laherparepvec
- •Woman of childbearing potential that is pregnant or breast-feeding, or planning to become pregnant or breast-feed during protocol treatment and for 3 months after last dose of Talimogene Laherparepvec
研究组 & 干预措施
Intralesional TALIMOGENE LAHERPAREPVEC with radiotherapy
Patients will receive 3 radiotherapy treatments (one treatment every 3-5 days) during weeks 3 and 4. The first treatment will occur 6 (+/- 2) hours after the Talimogene Laherparepvec administration at week 3.Talimogene Laherparepvec will be administered at weeks 0, 3, 5, 7, 9, 11, 13 and 15. The first dose of Talimogene Laherparepvec will be 10^6 plaque forming units (PFU)/mL, followed three weeks later by a dose of 10^8 pfu/mL.
干预措施: TALIMOGENE LAHERPAREPVEC (TVEC) (Drug)
Intralesional TALIMOGENE LAHERPAREPVEC with radiotherapy
Patients will receive 3 radiotherapy treatments (one treatment every 3-5 days) during weeks 3 and 4. The first treatment will occur 6 (+/- 2) hours after the Talimogene Laherparepvec administration at week 3.Talimogene Laherparepvec will be administered at weeks 0, 3, 5, 7, 9, 11, 13 and 15. The first dose of Talimogene Laherparepvec will be 10^6 plaque forming units (PFU)/mL, followed three weeks later by a dose of 10^8 pfu/mL.
干预措施: Hypofractionated Radiotherapy (Radiation)
Intralesional TALIMOGENE LAHERPAREPVEC without radiotherapy
Patients will receive Talimogene Laherparepvec alone, as described above, without radiotherapy.
干预措施: TALIMOGENE LAHERPAREPVEC (TVEC) (Drug)
结局指标
主要结局
Best Response
时间窗: 16 weeks
Overall subject level response is defined as partial or complete (\>50% or greater decrease in largest lesion) by the modified World Health Organization (mWHO) criteria, and will include measurements of tumor size by CT component of PET/CT, and clinically by digital photography.
次要结局
未报告次要终点