Pilot Safety and Feasibility Study of an In Vivo Sensitivity Screen Using a Direct Tumor Microinjection Technique and FDG-PET
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Mayo Clinic
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Incidence of drug sensitivity as measured by injection site skin reaction
研究概览
简要总结
This pilot phase I trial studies the side effects of direct tumor microinjection and fludeoxyglucose F-18 positron emission tomography (FDG-PET) in testing drug sensitivity in patients with non-Hodgkin lymphoma, Hodgkin lymphoma, or stage IV breast cancer that has returned after a period of improvement or does not respond to treatment. Injecting tiny amounts of anti-cancer drugs directly into tumors on the skin or in lymph nodes and diagnostic procedures, such as FDG-PET, may help to show which drugs work better in treating patients with non-Hodgkin lymphoma, Hodgkin lymphoma, or breast cancer.
详细描述
PRIMARY OBJECTIVE:
I. To assess the safety of in vivo in host drug sensitivity testing in patients with breast cancer and patients with lymphoma (nodal, extranodal masses, or cutaneous lesions).
SECONDARY OBJECTIVES:
I. To assess the feasibility of in vivo in host drug sensitivity testing in this patient population.
II. To identify targeted therapies with potential activity in relapsed lymphoma and metastatic breast cancer.
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
- •Age >= 18 years
- •Histologically proven of relapsed or refractory
- •Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) nodal or extranodal mass OR
- •Cutaneous T-cell lymphoma (CTCL) including mycosis fungoides (MF), as well as transformed MF OR
- •Breast adenocarcinoma with nodal or cutaneous metastases (stage 4)
- •NOTE: Patients must be refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition
- •NOTE: The patient must not be a candidate for any curative therapy or any known life-prolonging therapy
- •Cohort I: For nodal/extranodal mass, presence of lesions that are amenable for injections as determined by interventional radiology
- •NOTE: Nodal or extranodal mass must be palpable and easily accessible; masses such as mediastinum, retroperitoneum, within solid organs, spinal sites, central nervous system (CNS) sites, etc., are NOT allowed
- •Measurable disease:
- •For nodal or extranodal disease (lymphoma or breast): must have at least 2 lesions that are >= 20 mm (2.0 cm) in the longest diameter by physical exam and/or on cross-sectional imaging and measurable in two perpendicular dimensions per computed tomography PET-computed tomography (CT); For Cohort I, the lesions must be amenable to intralesional injections as determined by interventional radiology (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)
- •For cutaneous lesions (lymphoma or breast): at least two visible, non-infected skin lesions that are greater than 1 cm and are amenable to intralesional injection as determined by investigator
- •Candidate for further therapy and able to wait 7 days prior to start of next systemic therapy
- •Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
- •Platelet count >= 50,000/mm^3 (obtained =< 14 days prior to registration)
- •International normalized ratio (INR)/prothrombin time (PT) =< 1.5 (obtained =< 14 days prior to registration)
- •Negative serum or urine pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
- •Provide written informed consent
- •Willing to return to enrolling institution for follow-up
- •Willing to provide tissue samples for correlative research purposes
排除标准
- •Any of the following:
- •Pregnant persons
- •Nursing persons
- •Persons of childbearing potential who are unwilling to employ adequate contraception
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Systemic corticosteroids between pre-PET and post-PET evaluation and biopsy
- •Prohibited treatments and or therapies
- •Autologous stem cell transplant (ASCT) =< 12 weeks prior to registration
- •Prior chemotherapy =< 2 weeks prior to registration
- •Prior treatment with nitrosureas =< 4 weeks prior to registration
- •Therapeutic anticancer antibodies =< 2 weeks prior to registration
- •Radio- or toxin immunoconjugates =< 4 weeks prior to registration
- •Radiation therapy to the injected area =< 2 weeks prior to registration
- •Major surgery =< 2 weeks prior to registration
- •Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- •Requires anticoagulation that cannot be discontinued prior to biopsy
- •Note: Exception if able to hold antiplatelet agents 7 days prior to the injections and biopsy
- •NOTE: Low molecular weight heparin (LMWH) will be allowed for bridging if on warfarin
- •NOTE: Heparin for line patency without detectable lab abnormalities for coagulation will be allowed
研究组 & 干预措施
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Belinostat (Drug)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Carfilzomib (Drug)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Copanlisib Hydrochloride (Drug)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Daratumumab (Biological)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Fludeoxyglucose F-18 (Drug)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Gemcitabine Hydrochloride (Drug)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Nivolumab (Biological)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Obinutuzumab (Biological)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Pembrolizumab (Biological)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Positron Emission Tomography (Procedure)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Rituximab (Biological)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Romidepsin (Drug)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Saline (Other)
Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, copanlisib hydrochloride, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal/extranodal mass undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging photography and biopsy.
干预措施: Trastuzumab (Biological)
结局指标
主要结局
Incidence of drug sensitivity as measured by injection site skin reaction
时间窗: Up to 3 months
Skin reactions will be assessed using the Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) and will consist of any grade 3 or higher treatment-related pain, skin or subcutaneous tissue disorders. Incidence rates of skin reactions will be estimated by the number of patients with reactions divided by the total number of evaluable patients per disease type. Exact binomial 95% confidence intervals for the true incidence rate will be calculated.
次要结局
- Cutaneous response rate based upon the modified Severity Weighted Assessment Tool score(Up to 7 days post injection)
- Nodal disease response rate(Up to 5 days post injection)
- Incidence of adverse events(Up to 3 months)
- Feasibility(Up to 3 months)