Randomized Phase I Study Assessing the Safety and Tolerability Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at Completion of Interval Cytoreductive Surgery Compared to Surgery and Chemotherapy Prior to Surgery for Patients With Stage III/IV Ovarian Cancer Undergoing Neoadjuvant Chemotherapy.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Incidence of chemotherapy-related adverse events
研究概览
简要总结
This phase I trial studies the side effects of hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery in treating patients with stage III or IV ovarian, fallopian tube or peritoneal cancer receiving chemotherapy before surgery. Hyperthermic intraepithelial chemotherapy involves the infusion of heated cytotoxic chemotherapy that circulates into the abdominal cavity at the time of surgery. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery may kill more tumor cells compared to usual care.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of intravenous (IV) cisplatin on the day prior to interval cytoreductive surgery (CRS) to administration of hyperthermic intraepithelial chemotherapy (HIPEC) with cisplatin at the completion of interval cytoreductive surgery.
SECONDARY OBJECTIVES:
I. Feasibility of each of the treatment options. II. Treatment delays. III. Perioperative outcomes. IV. Quality of life/patient reported outcomes. V. Recurrence free survival (RFS) and overall survival (OS). VI. Changes to the gut MIcrobiome
OUTLINE:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Ability to understand (English-speaking), and willingness to sign a written, informed consent
- •Age > 18 years old
- •Newly diagnosed stage III or IV epithelial (serous, mucinous, or endometrioid) ovarian, fallopian tube or peritoneal cancer diagnosed by:
- •Biopsy/histology (either by interventional radiology or laparoscopy) OR
- •Cytology; If diagnosis is based on cytology the following criteria must be met:
- •Immunohistochemistry on the block from cytology to demonstrate Mullerian origin
- •Presence of pelvic mass AND CA 125 > 200kU/I AND CA125/CEA ratio > 25 at initial diagnosis
- •Omental cake or other metastases larger than 2 cm in the upper abdomen and/or regional lymph node metastasis irrespective of size (diagnosed by computed tomography [CT]/magnetic resonance imaging [MRI], ultrasound, or laparoscopy)
- •Patient planned for or currently receiving neoadjuvant chemotherapy due to the fact that optimal primary CRS was determined not to be feasible by the primary surgeon
- •Patient must be planned or scheduled to undergo interval cytoreductive surgery after cycle 3-4 of neoadjuvant surgery
- •Completion of three cycles of neoadjuvant chemotherapy (NACT) with standard therapy (carboplatin [area under the curve (AUC) 5-6] day [D]1 + paclitaxel [175 mg/m^2] D1 every 3 weeks)
- •Following 3-4 cycles of NACT partial or complete response
- •Following 3-4 cycles of NACT at least 50% decrease in CA-125 level between pre-cycle 1 and post-cycle 3/prior to surgery
- •Fit for major surgery, American Society of Anesthesiologists (ASA )1 or ASA 2
- •Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-2
- •Serum creatinine < 1.4 mg/dL
- •Creatinine clearance > 60 ml/min (Cockcroft-Gault formula)
- •White blood cell count > 3.5 x 10^9 cells/L
- •Absolute neutrophil count > 1.5 kg/ul
- •Platelets > 100,000/ul
- •Total bilirubin within 1.5 x normal institutional limits
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal
- •For quality of life assessment, baseline questionnaires should be filled in before randomization
排除标准
- •History of breast cancer or previous malignancy within 5 years prior to inclusion, with the exception of radically excised basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •Low grade serious carcinoma of the ovary or borderline ovarian tumors
- •History or current diagnosis of inflammatory bowel disease
- •History of allergic reactions to compounds of similar chemical or biologic composition to cisplatin, carboplatin, and paclitaxel
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
- •Patients in whom an optimal or complete cytoreduction cannot be performed will be excluded at the time of surgery and be replaced
研究组 & 干预措施
Arm I (carboplatin, paclitaxel, CRS, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Cytoreductive Surgery (Procedure)
Arm I (carboplatin, paclitaxel, CRS, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Quality-of-Life Assessment (Other)
Arm I (carboplatin, paclitaxel, CRS, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm I (carboplatin, paclitaxel, CRS, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Diagnostic Imaging (Procedure)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Cytoreductive Surgery (Procedure)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Paclitaxel (Drug)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Quality-of-Life Assessment (Other)
Arm I (carboplatin, paclitaxel, CRS, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Paclitaxel (Drug)
Arm I (carboplatin, paclitaxel, CRS, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Questionnaire Administration (Other)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Diagnostic Imaging (Procedure)
Arm I (carboplatin, paclitaxel, CRS, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Cisplatin (Drug)
Arm I (carboplatin, paclitaxel, CRS, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients receive cisplatin IV the day prior to CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Carboplatin (Drug)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Carboplatin (Drug)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Cisplatin (Drug)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Hyperthermic Intraperitoneal Chemotherapy (Drug)
Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)
OUTLINE:
Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval cytoreductive surgery (CRS)
Patients are randomized to 1 of 2 arms.
ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of CRS Patients undergo stool sample collection and diagnostic imaging throughout the trial.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Incidence of chemotherapy-related adverse events
时间窗: 30 days from perioperative treatment
Defined by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
次要结局
- Feasibility of chemotherapy immediately perioperatively(1 Day prior to surgery and 1 day of surgery)
- Percentage of patients in Arm C with a treatment free interval of < 8 weeks(Up to 1 year)
- Recurrence free survival(For 3-5 years after study)
- Tumor response(Up to 1 year)
- Quality of life (QOL) assessment EORTC QLQ-C30(Baseline up to 6 months post-treatment)
- Changes to the gut microbiome(Within one week of re-operative appointment, cycle 1 (each cycle is 28 days) of adjuvant chemotherapy and last cycle of adjuvant chemotherapy)
研究者
Floor Backes, MD
Principal Investigator
Ohio State University Comprehensive Cancer Center