Effect of Multi-modal Intervention Care on Cachexia in Patients With Advanced Cancer Compared to Conventional Management (MIRACLE)

Study Overview
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Brief Summary
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Background Cancer Cachexia (CC) is a multi-factorial process characterized by progressive weight loss, muscle mass and fat tissue wasting, and adversely affecting their quality of life and survival in patients with advanced stage of cancer. Megestrol acetate (MA), which can help maintain body weight in advanced cancer patients, has not been proven to be effective in improving quality of life or lean body mass. Furthermore, its use is often limited due to various adverse event such as Cushing syndrome, adrenal insufficiency, or thromboembolic risk. CC has a complex and multi-factorial pathophysiology, and there is no established standard treatment. Hypothesis CC is irreversible once it occurs and is also difficult to suppress its progression with any single treatment modality. The investigators hypothesized that a multi-modal intervention comprised of anti-inflammation, omega-3-fatty acids, oral nutritional supplement with counselling by nutritionist, physical exercise, psychiatric intervention as well as Bojungikki-tang which mediates immune-modulation and reverse both of chronic inflammation and wasting condition as a complementary and alternative medicine (CAM) could prevent the development of CC or improve the CC in advanced cancer patients during chemotherapy compared to those who received usual supportive.

Detailed Description
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[PICOT] Population: Patients with recurrent or metastatic solid cancer (gastric, colorectal, pancreas, biliary tract and lung) Intervention: Multimodal treatment Comparison: Conventional palliative care Outcome: Change of total lean body mass, Change of handgrip strength Time: 12 weeks of study period for each subject during the first- or second-line palliative chemotherapy

Official Title
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Effect of Multi-modal Intervention Care on Cachexia in Patients With Advanced Cancer Compared to Conventional Management (MIRACLE): An Open-label, Phase 2 Tria

Conditions
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Gastric Cancer, Colorectal Cancer, Pancreatic Cancer, Biliary Tract Cancer, Lung Cancer, Precachexia, Cachexia

Intervention / Treatment
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* Combination Product: Multi-modal intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 19 years of age Patients diagnosed with gastrointestinal (stomach, esophageal, direct colon, liver, pancreatic biliary tract) cancer and lung cancer Patients receiving first- or second-line palliative chemotherapy ECOG PS 0-2 Patients who were classified as normal, precachexia or cachexia according to the cachexia classification criteria Normal: Neither pre-cachexia Nor cachexia Precachexia: Weight loss ≤5%, Anorexia or glucose intolerance in last 6 months Cachexia: Weight loss >5%, or BMI <20 with weight loss >2% in last 6 months Adequate organ functions Exclusion Criteria: Patients with history of heart failure or currently being treated for heart failure Patients with SBP of 160 mmHg or higher or DBP of 100 mmHg or higher despite antihypertensive medication Patients with or have a history of bronchial asthma Patients with bowel obstruction Patients who have taken appetite stimulants or anabolic or anti-catabolic agents (eg. Megestrol acetate, progestational agents, etc.) within 30 days prior to the study enrollment Patients who received steroid treatment (> 10 mg/d prednisolone or equivalent) within 3 months prior to the study enrollment Patients who have taken nonsteroidal anti-inflammatory drugs or aspirin continuously for more than 1 week Patients with problems with taking non-steroidal anti-inflammatory drugs (NSAIDs) or those with uncontrolled diabetes due to digestive system diseases (gastric ulcer, gastrointestinal bleeding, etc.) Patients who are pregnant or breastfeeding, who have not used proper contraception (oral, injection, infusion or hormonal contraceptive methods, intrauterine devices and blocking methods) Patients who are taking anticoagulants (e.g. warfarin or heparin) Patients who have difficulty in oral administration Patients who have a history of hypersensitivity reactions such as asthma, hives, or allergic reactions to drugs containing ibuprofen, aspirin, and other nonsteroidal anti-inflammatory drugs (including COX-2 inhibitors) Patients who showed clinically significant hypersensitivity reactions to investigational products

Ages Eligible for Study
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Minimum Age: 19 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An open-label, randomized phase 2 trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIC<br>Multi-modal intervention | Combination Product: Multi-modal intervention<br>* Daily oral medications: ibuprofen 400 mg three times a day, omega-3-fatty acid 1 g twice a day, Bojungikki-tang 3.75g twice a day, oral nutritional supplement (HAMONILAN SOLN) 200 ml twice a day Weekly physical exercise by physiatrist (60 minutes per visit) Biweekly psychiatric intervention Nutritional counselling total four times during the study period<br>* Other names: oral nutritionalsupplement (HARMONILAN SOLN);|
| No Intervention: CPC<br>Conventional Palliative Care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median change (kilogram, kg) in total lean body mass (LBM) | The average of the change (kg) from baseline at week 7 and change from baseline at week 13 measured by DEXA (dual-energy X-ray absorptiometry) | Change of value between baseline and week13 | 
| Median change (kg) in handgrip strength | The average of the change (kg) from baseline at week 7 and change from baseline at week 13 measured by DEXA (dual-energy X-ray absorptiometry) | Change of value between baseline and week13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median change (kg) in fat mass | The average of the change (kg) from baseline at week 7 and change from baseline at week 13 measured by DEXA (dual-energy X-ray absorptiometry) | Change of value between baseline and week13 | 
| Median change (kg) in total body mass | The average of the change (kg) from baseline at week 7 and change from baseline at week 13 measured by DEXA (dual-energy X-ray absorptiometry) | Change of value between baseline and week13 | 
| Median change (kg) in body weight (kg) | The average of the change (kg) from baseline at week 7 and change from baseline at week 13 measured by the calibrated scale | Change of value between baseline and week13 | 
| Median change (kg) in lean body mass of trunk | The average of the change (kg) from baseline at week 7 and change from baseline at week 13 measured by DEXA (dual-energy X-ray absorptiometry) | Change of value between baseline and week13 | 
| Median change (kg) in lean body mass of both upper and lower extremities | The average of the change (kg) from baseline at week 7 and change from baseline at week 13 measured by DEXA (dual-energy X-ray absorptiometry) | Change of value between baseline and week13 | 
| Change from Anorexia-Cachexia scale | Functional Assessment of Anorexia/Cachexia Treatment (FAACT) version 4, The higher the score, the better the quality of life (QoL) with range 0-156. | Change of value between baseline and week 13 | 
| Change in quality of life (QoL) | The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 (Not at all), 2 (A little), 3 (Quite a bit) and 4 (Very much). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 (very poor) to 7 (excellent). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome. | Change of value between baseline and week 13 | 
| Rate of toxicity with clinical significance, and possible relationship to either study intervention | Assessed by the investigator, based on toxicity grade (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | Change of value between baseline and week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cachexia, chemotherapy, cancer, multi-modal intervention, NSAID