Ascites, Peritoneal Neoplasms, Yang Deficiency, Yin Deficiency
Conditions
Keywords
Peritoneal Carcinomatosis, Malignant Ascites, Modulated Electro-Hyperthermia, Traditional Chinese Medicine
Brief summary
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
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).
Interventions
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.
DIETARY_SUPPLEMENTTCM Herbal Decoction (Shi Pi)
Shi Pi Decoction can warm Yang, invigorate the spleen, promote Qi circulation to induce diuresis and treat Foot-Taiyin meridian in Gu Zhang.
DRUGIPCI (CDDP+5FU)
Intraperitoneal chemoinfusion of CDDP (30-60 mg) and 5-fluorouracil (500-600 mg/sqm).
Sponsors
Galenic Research Institute Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 8 weeks after start of treatment (4 weeks on completion of treatment) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Rate (AER) | During 4 weeks of treatment course and 4 weeks after treatment | 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. |
| Quality of Life (QoL) | 8 weeks after start of treatment (4 weeks on completion of treatment) | 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%. |
Countries
China
Participant flow
Recruitment details
From January 3, 2014 to December 20, 2014, 260 patients were recruited in Clifford Hospital. They were randomly allocated in two groups with 130 patients in each group.
Pre-assignment details
There was no any pre-assignment dropout or exclusion.
Participants by arm
| Arm | Count |
|---|---|
| Study Group 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.
Modulated Electro-Hyperthermia (mEHT): 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.
TCM Herbal Decoction (Shi Pi): Shi Pi Decoction can warm Yang, invigorate the spleen, promote Qi circulation to induce diuresis and treat Foot-Taiyin meridian in Gu Zhang. | 130 |
| Control Group 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.
IPCI (CDDP+5FU): Intraperitoneal chemoinfusion of CDDP (30-60 mg) and 5-fluorouracil (500-600 mg/sqm). | 130 |
| Total | 260 |
Baseline characteristics
| Characteristic | Control Group | Study Group | Total |
|---|---|---|---|
| 5-FU (Intraperitoneal Chemoinfusion) Dose Per Session | 548.5 mg/sqm STANDARD_DEVIATION 39.68 | 0 mg/sqm STANDARD_DEVIATION 0 | NA mg/sqm |
| Age, Continuous | 56.07 years STANDARD_DEVIATION 15.38 | 58.88 years STANDARD_DEVIATION 12.43 | 57.48 years STANDARD_DEVIATION 14.03 |
| CDDP (Intraperitoneal Chemoinfusion) Dose Per Session | 49.63 mg STANDARD_DEVIATION 10.19 | 0 mg STANDARD_DEVIATION 0 | NA mg |
| Interventions IPCI | 2 sessions | 0 sessions | NA sessions |
| Interventions mEHT | 0 sessions | 14 sessions | NA sessions |
| Interventions TCM | 0 sessions | 28 sessions | NA sessions |
| Karnofsky Performance Score 60 | 21 participants | 26 participants | 47 participants |
| Karnofsky Performance Score 70 | 47 participants | 50 participants | 97 participants |
| Karnofsky Performance Score 80 | 48 participants | 42 participants | 90 participants |
| Karnofsky Performance Score 90 | 14 participants | 12 participants | 26 participants |
| Metastases Bones | 25 participants | 22 participants | 47 participants |
| Metastases Celiac lymph nodes | 50 participants | 53 participants | 103 participants |
| Metastases Liver | 35 participants | 32 participants | 67 participants |
| Metastases Lungs | 20 participants | 23 participants | 43 participants |
| Primary Disease Colon Cancer | 37 participants | 34 participants | 71 participants |
| Primary Disease Endometrial Cancer | 5 participants | 9 participants | 14 participants |
| Primary Disease Gastric Cancer | 24 participants | 22 participants | 46 participants |
| Primary Disease Liver Cancer | 25 participants | 23 participants | 48 participants |
| Primary Disease Ovarian Cancer | 16 participants | 11 participants | 27 participants |
| Primary Disease Pancreatic Cancer | 8 participants | 13 participants | 21 participants |
| Primary Disease Rectal Cancer | 15 participants | 18 participants | 33 participants |
| Region of Enrollment China | 130 participants | 130 participants | 260 participants |
| Sex: Female, Male Female | 61 Participants | 72 Participants | 133 Participants |
| Sex: Female, Male Male | 69 Participants | 58 Participants | 127 Participants |
| Stage I | 0 participants | 0 participants | 0 participants |
| Stage II | 0 participants | 0 participants | 0 participants |
| Stage III | 76 participants | 66 participants | 142 participants |
| Stage IV | 54 participants | 64 participants | 118 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 130 | 16 / 130 |
| serious Total, serious adverse events | 0 / 130 | 0 / 130 |
Outcome results
Primary
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.
Time frame: 8 weeks after start of treatment (4 weeks on completion of treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Group | Objective Response Rate (ORR) | 77.7 percentage of participants |
| Control Group | Objective Response Rate (ORR) | 63.8 percentage of participants |
Comparison: Applies to Objective Response Rate (ORR)p-value: 0.014Chi-squared
Secondary
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.
Time frame: During 4 weeks of treatment course and 4 weeks after treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Adverse Events Rate (AER) | Abdominal pain (Gr. I) | 3 participants |
| Study Group | Adverse Events Rate (AER) | Damage of hepatic or renal function (Gr. I) | 0 participants |
| Study Group | Adverse Events Rate (AER) | Gastrointestinal Reactions (Gr. I) | 0 participants |
| Study Group | Adverse Events Rate (AER) | Bone marrow depression (Gr. I) | 0 participants |
| Study Group | Adverse Events Rate (AER) | All | 3 participants |
| Control Group | Adverse Events Rate (AER) | Bone marrow depression (Gr. I) | 6 participants |
| Control Group | Adverse Events Rate (AER) | All | 16 participants |
| Control Group | Adverse Events Rate (AER) | Abdominal pain (Gr. I) | 5 participants |
| Control Group | Adverse Events Rate (AER) | Gastrointestinal Reactions (Gr. I) | 3 participants |
| Control Group | Adverse Events Rate (AER) | Damage of hepatic or renal function (Gr. I) | 2 participants |
Comparison: Applies to All Adverse Events ratep-value: 0.0016Chi-squared
Comparison: Applies to Abdominal pain ratep-value: >0.05Chi-squared
Comparison: Applies to Gastrointestinal reactionsp-value: >0.05Chi-squared
Comparison: Applies to Damage of hepatic or renal functionp-value: >0.05Chi-squared
Comparison: Applies to Bone marrow depressionp-value: 0.0215Chi-squared
Secondary
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%.
Time frame: 8 weeks after start of treatment (4 weeks on completion of treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Group | Quality of Life (QoL) | Better QoL (KPS IR) | 49.2 percentage of participants |
| Study Group | Quality of Life (QoL) | No Change | 40.8 percentage of participants |
| Study Group | Quality of Life (QoL) | Worse QoL | 10 percentage of participants |
| Control Group | Quality of Life (QoL) | Better QoL (KPS IR) | 32.3 percentage of participants |
| Control Group | Quality of Life (QoL) | No Change | 52.3 percentage of participants |
| Control Group | Quality of Life (QoL) | Worse QoL | 15.4 percentage of participants |
Comparison: Applies to Better QoLp-value: 0.0053Chi-squared
Comparison: Applies to No Changep-value: 0.0527Chi-squared
Comparison: Applies to Worse QoLp-value: >0.05Chi-squared