Local mEHT + TCM Versus Intraperitoneal Chemoinfusion in Treatment of Malignant Ascites: Phase II RCT

Study Overview
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Brief Summary
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This trial studies efficacy and safety of combination of modulated electro-hyperthermia (mEHT) with Traditional Chinese Medicine (TCM) in treatment of peritoneal carcinomatosis with malignant ascites versus standard chemoinfusion (CDDP+5FU).

Detailed Description
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Conservative treatment of peritoneal carcinomatosis with malignant ascites (PCMA) is based on chemoinfusion with its inherent toxicity. There is a strong demand for a safe and non-toxic method of treatment of PCMA. The new technology of modulated electro-hyperthermia (mEHT) has proven efficacy in many advanced cancers with minimal side effects and synergy with Traditional Chinese Medicine (TCM). TCM has a long history of application at advanced cancer as a symptomatic treatment and enhancer of the general resistance of the organism. Shi Pi Decoction is supposed to be the optimum co-treatment of PCMA according to principles of TCM. Intraperitoneal chemoinfusion (IPCI) with cisplatin and fluorouracil is a widespread standard treatment of PCMA in China. This randomized II phase trial studies efficacy and safety of combination of mEHT with TCM in treatment of PCMA versus standard IPCI (CDDP+5FU).

Official Title
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Local Modulated Electro-Hyperthermia in Combination With Traditional Chinese Medicine Versus Intraperitoneal Chemoinfusion in Treatment of Peritoneal Carcinomatosis With Malignant Ascites: A Phase II Randomized Trial

Conditions
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Peritoneal Neoplasms, Ascites, Yang Deficiency, Yin Deficiency

Intervention / Treatment
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* Device: Modulated Electro-Hyperthermia (mEHT)
* Dietary Supplement: TCM Herbal Decoction (Shi Pi)
* Drug: IPCI (CDDP+5FU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed PC with malignant ascites. Karnofsky Performance Status (KPS) score ≥60%. Normal function of bone marrow. Predicted survival time >1 month. Written informed consent. Exclusion Criteria: Surgery within 3 weeks or not full recovery of postoperative suture. Active bleeding or vascular occlusion in the mEHT treatment area. Emotional instability. Impossibility to place the patient into the mEHT machine. Metallic implants or replacements in the treatment area. Electronic implanted devices anywhere. Missing or damaged heat-sense nerves or other field-sensitive issues in the treatment area. Very low white blood cell count (<1.5×10(9)/L), agranulocytosis (<0.5×10(9)/L) or severe anemia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Modulated Electro-Hyperthermia (mEHT): 150 Watt x 60 min/session every 2nd day for 4 weeks (14 sessions); TCM Herbal Decoction: Shi Pi Decoction administered orally twice a day (200 mL x 2) 30 min after breakfast and supper, for 4 weeks. | Device: Modulated Electro-Hyperthermia (mEHT)<br>* MEHT is a descendant of hyperthermia initially based on nano-thermal but not temperature-dependent effects of electromagnetic fields and special fractal modulation, whose effect could 3-4 times exceed the effect of the overall heating (macroscopic temperature elevation). MEHT does not require hyperthermia-range temperatures and could be performed safely without invasive thermal control. EHY-2000 local machine is used for mEHT in the trial.<br>* Other names: Oncothermia;Dietary Supplement: TCM Herbal Decoction (Shi Pi)<br>* Shi Pi Decoction can warm Yang, invigorate the spleen, promote Qi circulation to induce diuresis and treat Foot-Taiyin meridian in Gu Zhang.<br>* Other names: Shi Pi Decoction;|
| Active Comparator: Control Group<br>IPCI: CDDP (30-60 mg) with 5FU (500-600 mg/sqm of body surface), both dissolved in 100 mL of normal saline, after abdominal paracentesis and catheterization with following closed drainage of the ascites up to small amount of remaining liquid. After IPCI, the catheter occluded. Administered biweekly during four weeks of the course, totally two times. | Drug: IPCI (CDDP+5FU)<br>* Intraperitoneal chemoinfusion of CDDP (30-60 mg) and 5-fluorouracil (500-600 mg/sqm).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate (ORR) = Complete Remission (CR) + Partial Remission (PR) WHO criteria of therapeutic effect evaluation at malignant ascites: Complete Remission (CR): complete absorption of ascites with no obvious regeneration for more than 1 month. Partial Remission (PR): more than 50% reduction of ascites, with obvious relief of abdominal distention, with maintenance of less than moderate volume of ascites under ultrasound detection for more than 1 month. No Change (NC): less than 50% reduction of ascites, or no obvious reduction of ascites under ultrasound detection, or even increase of ascites, with obvious abdominal distention. | 8 weeks after start of treatment (4 weeks on completion of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events Rate (AER) | Common Terminology Criteria for Adverse Events (CTCAE) (v4.03: June 14, 2010) U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES, National Institutes of Health, National Cancer Institute. | During 4 weeks of treatment course and 4 weeks after treatment | 
| Quality of Life (QoL) | Karnofsky Performance Score Improvement Rate (KPS IR) Improvement: increase of KPS for ≥10% after treatment. Worsening: reduction of KPS for ≥10% after treatment. NC: change of KPS for <10%. | 8 weeks after start of treatment (4 weeks on completion of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peritoneal Carcinomatosis, Malignant Ascites, Modulated Electro-Hyperthermia, Traditional Chinese Medicine