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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Lung Cancer; Cachexia; Biliary Tract Cancer; Precachexia
• Intervention / Treatment: Combination product: Multi-modal intervention

Detailed Description

[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

• Study Type: Interventional
• Enrollment (Anticipated): 112
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chi Hoon Maeng, M.D.; Phone Number: +82-2-958-2965; Email: mchihoon@khu.ac.kr
• Study Contact Backup: Name: Bo-Hyung Kim, M.D.; Phone Number: +82-2-958-9326; Email: bhkim98@khu.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 02447
    • Recruiting
    • Kyung Hee University Hospital
    • Contact: Chi Hoon Maeng, M.D.; Phone Number: +82-2-958-2965; Email: mchihoon@khu.ac.kr
    • Contact: Bo-Hyung Kim, M.D.; Phone Number: +82-2-958-9326; Email: bhkim98@khu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MIC; Multi-modal intervention	Combination product: Multi-modal intervention; 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; Other Names: ibuprofen (Brufen); omega-3-fattyacid (Omacor); Bojungikki-tang (Kracie Bojungikgitang Extract Fine Granule); oral nutritionalsupplement (HARMONILAN SOLN)
No Intervention: CPC; Conventional Palliative Care

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kil Yeon Lee
• Collaborators: National Research Foundation of Korea
• Investigators: Principal Investigator: Kil Yeon Lee, M.D., Kyung Hee University Hospital

Publications and helpful links

General Publications

• Maeng CH, Kim BH, Chon J, Kang WS, Kang K, Woo M, Hong IK, Lee J, Lee KY. Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): an open-label, parallel, randomized, phase 2 trial. Trials. 2022 Apr 11;23(1):281. doi: 10.1186/s13063-022-06221-z.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2020
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 28, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 28, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: chemotherapy; cancer; NSAID; cachexia; multi-modal intervention
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Nutrition Disorders; Body Weight; Body Weight Changes; Biliary Tract Diseases; Emaciation; Weight Loss; Wasting Syndrome; Cachexia; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: KHMC-HUMANITAS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After anonymizing the patient's confidential information, it can be converted into data and shared.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No