Phase II Study for the Evaluation of Efficacy of Pembrolizumab (MK-3475) in Patients With Rare Tumors
概览
- 阶段
- 2 期
- 干预措施
- Laboratory Biomarker Analysis
- 疾病 / 适应症
- Advanced Malignant Solid Neoplasm
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 157
- 试验地点
- 1
- 主要终点
- Non-progression Rate (NPR) at 27 Weeks by irRECIST
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
This phase II trial studies how well pembrolizumab works in treating patients with rare tumors that cannot be removed by surgery or have spread to other parts of the body. Monoclonal antibodies, such as pembrolizumab, may block specific proteins found on white blood cells which may strengthen the immune system and control tumor growth.
详细描述
PRIMARY OBJECTIVES: I. To obtain early indication of efficacy by evaluation of non-progression rate (NPR) at 27 weeks as defined as the percentage of patients who are alive and progression-free at 27 weeks as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 or immune-related(ir)RECIST or method of tumor evaluation criteria best suitable and accepted for the tumor type evaluated in patients with advanced tumor types receiving pembrolizumab. SECONDARY OBJECTIVES: I. To correlate efficacy by evaluation of tumor size to programmed cell death 1 ligand 1 (PD-L1) status among patients with advanced tumor types receiving pembrolizumab. II. To evaluate safety and tolerability of pembrolizumab in patients with advanced tumors. III. To evaluate the percentage of patients with objective response (complete response \[CR\] or partial response \[PR\]), clinical benefit (CR, PR, or stable disease \[SD\] \>= 4 months), progression free survival (PFS), overall survival (OS), and duration of response (DOR) as assessed by RECIST v1.1 in patients with advanced tumor types receiving pembrolizumab. IV. To evaluate the percentage of patients with objective response (CR or PR), clinical benefit (CR, PR, or SD \>= 4 months), PFS, and DOR as assessed by irRECIST in patients with advanced tumor types receiving pembrolizumab. V. To correlate the NPR at 27 weeks (9 cycles), objective response (CR or PR), clinical benefit CR, PR, or SD \>= 4 months), PFS, OS, and DOR to PD-L1 status among patients with advanced tumor types receiving pembrolizumab. EXPLORATORY OBJECTIVES: I. To evaluate the potential role of tumor-associated immune biomarkers for prediction of therapy effectiveness in patients with advanced tumor types receiving pembrolizumab. II. To correlate the potential role of tumor-associated immune biomarkers for prediction of therapy effectiveness to PD-L1 status among patients with advanced tumor types receiving pembrolizumab. III. To identify imaging characteristics associated with immunological changes in tumor following treatment with pembrolizumab. IV. To compare tumor mutation burden and serial assessment of mutation status in biopsies obtained at baseline and progression in patients with advanced tumor types receiving pembrolizumab. V. To evaluate patient-reported outcomes (PRO) utilizing the National Cancer Institute (NCI) Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaires. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or toxicity. Patients with clinical response or disease stabilization may continue treatment for up to an additional 12 months. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
研究者
入排标准
入选标准
- •Be willing and able to provide written informed consent/assent for the trial
- •Have measurable disease based on RECIST 1.1 or irRECIST; only cohort 9 and 10 can have evaluable disease (non-measurable lesions); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions; patients may have bone metastatic disease evaluable according to tumor evaluation criteria best suitable and accepted for the tumor type evaluated
- •Have one of the following advanced (unresectable and/or metastatic) solid tumor indications that has progressed following standard therapies, where standard therapies are available:
- •Squamous cell carcinoma of the skin
- •Small cell malignancies of non-pulmonary origin
- •Adrenocortical carcinoma
- •Medullary renal cell carcinoma
- •Carcinoma of unknown primary
- •Penile carcinoma
- •Vascular sarcoma
排除标准
- •Is currently participating and receiving study therapy or concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment at the time of administration of first dose of trial treatment; continuation of hormone replacement therapy is permitted; stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a gonadotrophin releasing hormone \[GnRH\] agonist), ovarian, or breast cancer are not exclusionary
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- •Has a known history of active TB (bacillus tuberculosis)
- •Hypersensitivity to pembrolizumab or any of its excipients
- •Has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- •Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and diseases for which the treatment could reasonably include pembrolizumab and are not part of the excluded tumor type list or not eligible for the phase I trial
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; immunosuppressive corticosteroid doses (\> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of pembrolizumab; Note: corticosteroids given within 24 hours of an imaging study for purposes of pre-medication in patients with hypersensitivity to radiologic contrast agents are allowed
- •Has known history of, or any evidence of active, non-infectious pneumonitis
- •Has an active infection requiring systemic therapy
研究组 & 干预措施
Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or toxicity. Patients with clinical response or disease stabilization may continue treatment for up to an additional 12 months.
干预措施: Laboratory Biomarker Analysis
Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or toxicity. Patients with clinical response or disease stabilization may continue treatment for up to an additional 12 months.
干预措施: Pembrolizumab
Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or toxicity. Patients with clinical response or disease stabilization may continue treatment for up to an additional 12 months.
干预措施: Questionnaire Administration
结局指标
主要结局
Non-progression Rate (NPR) at 27 Weeks by irRECIST
时间窗: At 27 weeks
Non-progression rate (NPR) at 27 weeks was defined as the percentage of efficacy evaluable patients who were alive and progression-free at 27 weeks as assessed by irRECIST Progression is defined using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), as an increase ≥ 20% (minimum 5 mm) in total measured tumor burden compared with nadir or progression of non-target lesions or new lesion
次要结局
- Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)(Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.)
- Progression-free Survival (PFS) Using RECIST v1.1(Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.)
- Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1)(Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.)
- Number of Patients Who Experienced Treatment-related Adverse Event (TRAE)(First day of administration of study medication through 30 days following last dose, an average of 4 years.)
- Clinical Benefit Rate (CBR) Using RECIST v1.1(Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.)
- Immune-related Clinical Benefit Rate (CBR) Using irRECIST(First day of administration of study medication through 30 days following last dose, an average of 4 years.)
- Immune-related Progression-free Survival (PFS) Using irRECIST(Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks.)
- Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.)