Individualized Response Assessment to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Primaries
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- To determine the correlation between ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki-67
研究概览
简要总结
Background:
Cytoreductive surgery (CRS) removes tumors in the abdomen. HIPEC is hyperthermic (heated) chemotherapy that washes the inside of the abdomen. CRS with HIPEC may help people with peritoneal carcinomatosis. These are tumors that have spread to the lining of the abdomen from other cancers. Researchers think they can improve the results of CRS with HIPEC treatment on these tumors by choosing the chemotherapy drugs used in HIPEC.
Objective:
To see if HIPEC after CRS can be improved, using either a model called the SMART (Sustained Microenvironment for Analysis of Resected Tissue) System or using 3-D cell culture (organoid) models, in order to test different chemotherapy drugs on tumors that were surgically removed prior to HIPEC treatment (these models are not attached to the body) versus tumors that were treated with HIPEC while still inside the body before being immediately surgically removed.
Eligibility:
Adults ages 18 and older who have peritoneal carcinomatosis that cannot be fully removed safely with surgery.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Electrocardiogram (EKG)
Computed tomography (CT) scan
Other imaging scans, as needed
Tumor biopsy, if needed
Laparoscopy (small cuts are made in the abdomen, and a tube with a light and a camera is used to see the organs in the abdomen), if needed
Participants will enroll in NIH protocol #13C0176. This allows their tumor samples to be used in future research.
Some screening tests may be repeated in the study.
Participants will have CRS. As many of their visible tumors will be removed as possible during surgery except for a few specific tumors left to receive the HIPEC treatment. Then they will receive HIPEC and the remaining tumors will be immediately removed. Participants will be in the hospital for 7-21 days after this surgery (CRS with HIPEC).
Participants will give tumor, fluid samples (from the abdomen during surgery), blood, saliva, cheek swab, and stool for research. They will complete surveys about their health and quality of life.
Participants with peritoneal mesothelioma (mesothelioma primary only) will have genetic (DNA) testing to determine clinical (CLIA level) germline BAP1 status for research use.
Participants will have follow-up visits for up to 5 years from CRS with HIPEC.
If there is disease progression, participants may have CRS with HIPEC again. Participants will then have follow-up visits for up to 5 years from the date of last CRS with HIPEC.
详细描述
Background:
Peritoneal carcinomatosis is uniformly fatal if untreated; improved outcomes are seen with aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).
The selection of chemotherapeutic agent for HIPEC is largely based on primary tumor histology and provider preference as opposed to knowledge of the potential efficacy of a specific agent for an individual patient.
HIPEC is intended to target small or microscopic residual disease following complete cytoreduction; however, the actual efficacy and additional benefit of HIPEC is in question.
Tissue response to simulated ex vivo HIPEC treatment in the SMART System or 3-D cell culture (organoid) models could inform chemotherapeutic agent selection for subsequent cytoreduction and intra-operative in vivo HIPEC treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Confirmation of peritoneal carcinomatosis from peritoneal mesothelioma or atypical mesothelial proliferation, or from appendiceal, colorectal, or ovarian, histologies by the Laboratory of Pathology, NCI.
- •Measurable or evaluable disease as defined by RECIST v1.
- •criteria and/or by peritoneal carcinomatosis index (PCI) score.
- •Participants must be assessed to be able to undergo optimal cytoreduction (i.e., completeness of cytoreduction score of 1 or 0) with laparoscopically assessed PCI score threshold as indicated below:
- •Primary Histology: Appendiceal/Colorectal/Ovarian / PCI Cutoff for Eligibility: Total Score < 20 (out of 39 possible points)
- •Primary Histology: Mesothelioma or atypical mesothelial proliferation / PCI Cutoff for Eligibility: Total Score <= 30 (out of 39 possible points)
- •Age >= 18 years.
- •ECOG performance status <= 1 (Karnofsky >= 80%).
- •Participants must have adequate organ and marrow function as defined below:
- •Absolute neutrophil count >= 1,000/mcL
- •Platelets >= 75,000/mcL
- •Total bilirubin within <=1.5x institutional upper limit of normal (ULN)
- •AST (SGOT)/ ALT (SGPT) <= 3x institutional upper limit of normal (ULN), or <= 5.0x ULN in participants with liver metastases (only)
- •Creatinine within normal institutional limits
- •-Creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal calculated using eGFR.
- •Because therapeutic agents used in this trial are known to be teratogenic, individuals of child-bearing potential (IOCBP) and individuals who are able to father a child must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 180 days after last study treatment.
- •Ability of participant to understand and the willingness to sign a written informed consent document.
- •Ability and willingness of the participant to co-enroll on the tissue collection protocol 13C0176, Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors .
排除标准
- •Participants with known extra-abdominal metastatic disease from the participant s appendiceal, colorectal, ovarian, or peritoneal mesothelioma primary.
- •Participants who have received intraperitoneal chemotherapy or other anti-cancer therapy within the last 4 weeks prior to the start of study treatment.
- •Participants who have undergone major surgery within the last 12 weeks prior to the start of study treatment.
- •History of allergic reactions attributed to platinum-containing compounds.
- •History of dihydropyrimidine dehydrogenase deficiency (only participants with appendiceal or colorectal cancer).
- •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.
- •Pregnant individuals are excluded from this study because the protocol involves major abdominal surgery and chemotherapeutic agents with the potential for teratogenic or abortifacient effects. Note: Due to an unknown but potential risk for adverse events in nursing infants secondary to treatment of the participant, nursing (including breastfeeding) should be discontinued if the participant is undergoing treatment (i.e., nursing participants must agree to discontinue nursing activities).
- •HIV-positive participants with detectable viral load despite antiretroviral therapy are ineligible because of participants increased risk of lethal infections when treated with marrow-suppressive therapy. HIV-positive participants who have undetectable viral load on antiretroviral therapy may be considered for this study only after consultation with a NIAID physician.
研究组 & 干预措施
1/ HIPEC: Oxaliplatin Randomized treatment assignment
HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned
干预措施: Hyperthermic Intraperitonial Chemotherapy (Procedure)
2/ HIPEC: Mitomycin C Randomized treatment assignment
HIPEC with intraperitoneal mitomycin C, randomly assigned
干预措施: Hyperthermic Intraperitonial Chemotherapy (Procedure)
3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment
HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned
干预措施: Hyperthermic Intraperitonial Chemotherapy (Procedure)
3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment
HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned
干预措施: Cisplatin (Drug)
4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment
HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned
干预措施: Cisplatin (Drug)
3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment
HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned
干预措施: Sodium Thiosulfate (Drug)
4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment
HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned
干预措施: Mitomycin C (Drug)
3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment
HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned
干预措施: Doxorubicin (Drug)
4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment
HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned
干预措施: Hyperthermic Intraperitonial Chemotherapy (Procedure)
4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment
HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned
干预措施: Sodium Thiosulfate (Drug)
1/ HIPEC: Oxaliplatin Randomized treatment assignment
HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned
干预措施: Oxaliplatin (Drug)
1/ HIPEC: Oxaliplatin Randomized treatment assignment
HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned
干预措施: 5-Fluorouracil (Drug)
2/ HIPEC: Mitomycin C Randomized treatment assignment
HIPEC with intraperitoneal mitomycin C, randomly assigned
干预措施: Mitomycin C (Drug)
结局指标
主要结局
To determine the correlation between ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki-67
时间窗: approx. 4 days post-HIPEC
percent necrosis and Ki-67 scores will be obtained and used to determine the correlation between each measure by ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and by in vivo intra-operative HIPEC
次要结局
- To measure Quality of Life by FACT-C and EQ-5D-5L(baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years)
- To estimate the peritoneal progression-free survival probability(baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years)
- To assess germline BAP1 status as a prognostic indicator for progression-free survival (PFS) in participants with peritoneal mesothelioma treated with CRS and HIPEC(baseline)
- To evaluate overall survival for up to 5 years after (last) CRS and HIPEC(death or 5 years post-treatment)