A Phase 1 Study of Talimogene Laherparepvec and Panitumumab in Patients With Locally Advanced Squamous Cell Carcinoma of the Skin (SCCS)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 5
- 主要终点
- Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0
研究概览
简要总结
This phase I trial studies the side effects and how well talimogene laherparepvec and panitumumab work in treating patients with squamous cell carcinoma of the skin that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic). Talimogene laherparepvec is a type of vaccine made from a gene-modified virus that may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talimogene laherparepvec and panitumumab may work better in treating patients with squamous cell carcinoma of the skin compared to panitumumab alone.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety of the combined treatment of talimogene laherparepvec and panitumumab.
II. To determine the preliminary efficacy of the combined treatment of talimogene laherparepvec and panitumumab, in comparison to single-agent panitumumab by historical control.
SECONDARY OBJECTIVES:
I. To assess the clinical efficacy of panitumumab in combination with intratumoral talimogene laherparepvec in terms of immune-related progression-free survival (irPFS) at 12 months, progression-free survival (PFS) hazard ratio, overall response rate (ORR), 1-year survival, overall survival (OS) and time to resectability.
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
- •Histologically confirmed squamous cell carcinoma of the skin (SCCS) that is a) locally advanced or metastatic for which curative surgery or radiation would be difficult or impossible, or b) recurrent after initial surgery, chemotherapy, or radiation therapy, or c) considered to have aggressive features including the following: tumors 2 cm or more, tumors invading deep tissues such as muscle, cartilage or bone; tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes. Patients may have had prior surgical interventions or been treated with investigational agents with residual or recurrent disease
- •Tumor suitable for direct or ultrasound-guided injection defined as at least one cutaneous, subcutaneous, or nodal lesion, or aggregate of lesions, >= 10 mm in diameter
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •No prior treatment with panitumumab or talimogene laherparepvec for advanced disease
- •Prior surgery or radiation is allowed if there is documented progression in the radiated/resected area or elsewhere by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v) 1.1
- •Measurable disease by RECIST criteria v 1.1
- •Patients with a history of hematologic or solid organ transplant will be considered if they do not require high dose steroids or high dose immunosupressants for disease control or control of transplant rejection, and have adequate hematologic, renal, and hepatic function as specified below. Current medications must be reviewed with transplant pharmacy team to exclude potentially serious interactions and case discussed with the study principal investigator (PI)
- •Second primary malignancy only if treatment would interfere with the patient?s participation in this trial in the opinion of the treating physician. Clear exceptions are 1) patient had a second primary malignancy but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g., in situ carcinoma of the cervix) and, 3) additional skin cancers that have been definitively treated by surgery and/or radiation. Patients with chronic lymphocytic leukemia will be allowed if their blood counts are within acceptable hematologic parameters and if they are not currently requiring cytotoxic or biologic anticancer treatment (supportive treatment such as intravenous immunoglobulin [IVIG] is permitted)
- •Patients with autoimmune disorders will be considered if they do not require high dose steroids or other immunosuppressants for disease control. Prednisone in daily doses up to 10 mg and inhaled steroids are acceptable
- •Absolute neutrophil count (ANC) >= 1500/uL
- •Platelet count >= 100,000/mm^2
- •Hemoglobin >= 9 g/dL
- •Total bilirubin < 1.5 x institutional upper limit of normal (ULN); if patient has conditions of congenital hyperbilirubinemia, then patient must have isolated hyperbilirubinemia (e.g., no other liver function test abnormalities) with maximum bilirubin < 2 x institutional ULN
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x institutional ULN in absence of liver metastases; =< 5 x ULN in presence of liver metastases
- •Alkaline phosphatase < 2.5 x institutional ULN
- •Creatinine < 1.5 x institutional ULN or calculated creatinine clearance >= 60 mL/min as estimated using the Cockcroft-Gault formula
排除标准
- •Pregnant women. Women of childbearing age must be willing to undergo a pregnancy test prior to therapy and to use adequate contraception (e.g., hormonal or barrier method of contraception or abstinence) for the duration of the study and 6 months thereafter. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Menopausal status will be defined as one or more of successful hysterectomy, bilateral tubal ligation or bilateral oophorectomy, amenorrhea >= 12 consecutive months without another cause, or a documented serum follicle stimulating hormone (FSH) >= 35 mIU/mL
- •Tumor not suitable for direct or ultrasound-guided injection
- •Prior treatment with talimogene laherparepvec for advanced disease
- •Patients with active, uncontrolled infections including active herpetic infections or chronic herpetic infections requiring anti-viral therapy (e.g., acyclovir)
- •Patients without adequate organ function as documented above
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab, talimogene laherparepvec or other agents used in the study
- •History of interstitial pneumonitis, pulmonary fibrosis, or evidence of interstitial pneumonitis
研究组 & 干预措施
Treatment (talimogene laherparepvec, panitumumab)
Patients receive talimogene laherparepvec IM on day 1. Patients then receive talimogene laherparepvec IM and panitumumab IV over 30-90 minutes on day 22. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive up to 3 additional cycles of treatment per physician discretion.
干预措施: Panitumumab (Biological)
Treatment (talimogene laherparepvec, panitumumab)
Patients receive talimogene laherparepvec IM on day 1. Patients then receive talimogene laherparepvec IM and panitumumab IV over 30-90 minutes on day 22. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive up to 3 additional cycles of treatment per physician discretion.
干预措施: Talimogene Laherparepvec (Biological)
结局指标
主要结局
Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0
时间窗: Up to 30 days
Number of participants who experience adverse effects greater than or equal to a grade three as defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Grade 1-4, with 4 being the most severe.
Response Rate to Panitumumab as Measured by Evaluation of the Criteria in Solid Tumors (RECIST) 1.1.
时间窗: Up to two years
Response will be evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Changes in the largest diameter (unidimensional measurement)of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used for tumor measurements.
次要结局
- Deoxyribonucleic Acid Mutation Signature in Tumor Tissue(Up to two years)
- Durable Response Rate Based on Simons Two-stage Design(Up to two years)
- Best Overall Response Rate (ORR) of Participants From Start to Progression of Disease(Up to two years)
- Duration of Response Based on Simons Two-stage Design(Time from initial response until document progression up to two years)
- Progression-free Survival (PFS) to Assess Participants Progressive Free-survival(From date of enrollment to the date of death or progression, whichever occurred earlier assessed up to 2 years)
- Change in Overall Survival (OS) Measured by the Kaplan-Meier(From date of enrollment to the date of death or date last known alive, whichever comes first, assessed up to assessed up to two years)
- Mutation Load in Tumor Tissue Measured by Next Generation Sequencing(Up to two years)
- Expression of Cytokines in Tumor Tissue(Up to two years)
- Expression of Cytokines in Peripheral Blood(Up to two years)
- Messenger Ribonucleic Acid Signature in Tumor Tissue Measured by Nanostring Technology(Up to two years)
- Immune Cell Populations in Tumor Tissue(Up to two years)
- Immune Cell Populations Peripheral Blood as Measured by Flow Cytometry(Up to two years)
- Time to Resectability(Up to two years)
- Pathologic Complete Response Rate(Up to two years)
研究者
CINJRegulatory
Principal Investigator is deceased - Professor and Chief of Melanoma and Soft Tissue Sarcoma
Rutgers Cancer Institute of New Jersey