Herbal Treatment to Improve Chemotherapy Delivery (HATCHED)

Effect of TCM-TSKSR on Completion Rates of Chemotherapy in Patients With Stage II & III Colon Cancer: A Randomized Placebo-Controlled Clinical Trial

This study is designed to:(1) determine the efficacy of Traditional Chinese Medicine (TCM) 'Tonifying Spleen and Kidney Sequential Regimen' (TSKSR) in improving the completion rate of 8-cycle CapeOX chemotherapy in patients with stage II (high-risk)& III colon cancer;(2) evaluate the efficacy of the TCM-TSKSR on adverse events of CapeOX chemotherapy and it's impact on patients' quality of life (QoL).A randomized,double-blinded,placebo-controlled clinical trial including seven centers will be conducted in Mainland China.The study will enroll patients with stage II (high-risk)& III colon cancer who have completed radical surgery and are going to receive CapeOX chemotherapy.All participants will receive chemotherapy as prescribed by their treating physicians and be randomly assigned to either concurrent use of TCM-TSKSR or placebo.

Study Overview

• Status: Unknown
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: Tonifying Spleen and Kidney Sequential Regimen; Drug: Placebo of 'Tonifying Spleen and Kidney Sequential Regimen

Detailed Description

CapeOX chemotherapy is a combination therapy of Oxaliplatin 130mg/m^2 IV on 1st day and Capecitabine 1000mg/m^2 PO twice daily from 1th day to 14th day,21 days for each course of treatment.Adverse effects of chemotherapy,such as myelosuppression and gastrointestinal reactions,may lead to dose reductions,treatment delays or even discontinuation among cancer patients. According to IDEA study,the completion rate of 8-cycle CapeOX chemotherapy in colorectal cancer patients is 64%,which means that nearly 4 in 10 patients could not complete adjuvant chemotherapy as planned,which may negatively impact patients' survival outcomes.Some prior studies have shown that TCM can improve patients' symptom control and QoL during adjuvant chemotherapy,which may further improve the completion of adjuvant chemotherapy. However,there is a lack of definitive evidence to evaluate the effects of TCM in stage II(high-risk)& III colon cancer patients who receive adjuvant chemotherapy after radical surgery.The study will be conducted between 2018 and 2021.Four hundred participants will be enrolled and randomly assigned to either the experimental group or the control group.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yufei Yang, M.D.; Phone Number: 8613701366913; Email: yyfwdbwyy@126.com
• Study Contact Backup: Name: Yun Xu, M.D.; Phone Number: 8615210775378; Email: xyxiao78@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Aiwen Wu, M.D.; Phone Number: 13911577190
    • Beijing, Beijing, China, 100091
      • Recruiting
      • Oncology Department of Xiyuan Hospital of China Academy of Chinese Medical Sciences
      • Contact: Yufei Yang, M.D.; Phone Number: 86 10 62835355; Email: yyfwdbwyy@126.com
    • Beijing, Beijing, China, 100020
      • Recruiting
      • Beijing Chao Yang Hospital
      • Contact: Minzhe Li, M.D.
    • Beijing, Beijing, China, 100025
      • Recruiting
      • Civil Aviation General Hospital
      • Contact: Jianping Cheng
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Recruiting
      • Chongqing University Cancer Hospital
  • Guangzhou
    • Guangdong, Guangzhou, China, 510120
      • Recruiting
      • Guangdong Provincial Hospital of Traditional Chinese Medicine
      • Contact: Jin Wan, M.D.
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Provincial People's Hospital
      • Contact: Shundong Cang, M.D.; Phone Number: 13592675836
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • The Third People's Hospital of Zhengzhou
      • Contact: Yang Cao
    • Zhengzhou, Henan, China, 450007
      • Recruiting
      • Zhengzhou Hospital of Traditional Chinese Medicine
      • Contact: Baozhu Zeng; Phone Number: 13838520891
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital of Traditional Chinese Medicine
      • Contact: Peng Shu, M.D.
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Shanghai Zhongshan Hospital
      • Contact: Tianshu Liu, M.D.
  • Tianjin
    • Tianjin, Tianjin, China, 300121
      • Recruiting
      • Tianjin Union Medical Center
      • Contact: Huaqing Wang, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with pathological diagnosis of colon cancer; no residual tumor at the resection margin.

• tumor-node-metastasis(TNM)Stage II (high-risk)or III colon cancer according to 8th edition of American Joint Committee on Cancer(AJCC)Staging Manual. High-risk stage II disease is characterized by at least one of the following:

  1. T4 tumor,
  2. inadequately sampled nodes (<12 lymph nodes),
  3. clinical presentation with bowel obstruction or perforation,
  4. poorly differentiated histology ,exclusive of those cancers that are High degree of microsatellite instability(MSI-H),
  5. lymphovascular invasion,perineural invasion(PNI).
• Underwent radical surgery no more than six weeks ago and plan to start chemotherapy.
• Have not been enrolled in other therapeutic clinical trials within the near 30 days.
• Age between 18 to 75 years; All genders; Eastern Cooperative Oncology Group - performance status(ECOG-PS)from 0 to 2; Women who are pregnant, lactating or of reproductive age are not eligible, while those of reproductive age using secure contraceptives are eligible.
• No history of previous malignancy other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin, unless there has been a disease-free interval of at least 5 years.
• Laboratory testing: blood routine examination: WBC≥3.5×109/L，NEUT≥1.5×109/L,PLT≥100×109/L,HGB≥90g/L;biochemical tests:TBIL≤1.5×ULN,AST(SGOT),ALT(SGPT)≤2.5×ULN,Scr≤1.5×ULN;CEA after surgery was normal.
• Consented.
• Agree not to be enrolled in other interventional studies during the research.

Exclusion Criteria:

• Patients not suitable for chemotherapy of CapeOX ,which will be determined by the investigator or the attending physician.
• Clinically relevant cardiovascular and/or cerebrovascular disease,active hepatitis,severe abnormalities in liver/ renal function tests.
• Known allergy to any of the components of study drug.
• Those who cannot take the study drug orally because of bowel obstruction and/or require for peripheral vein nutrition.
• Malabsorption or diseases that affect the absorption.
• Unstable situations or situations that may endanger the safety of patients and their compliance, such as severe mental illness,schizophrenia.
• Colostomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TCM group; Tonifying Spleen and Kidney Sequential Regimen(TSKSR) will be prescribed to the participants in each course of chemotherapy.	Drug: Tonifying Spleen and Kidney Sequential Regimen; TSKSR will be given to the participants as follows:Liu-jun-an-wei Granule,1 pack each time,twice a day,PO,from 0 to 6th day of chemotherapy and Qi-tu-er-zhi Granule,1 pack each time,twice a day,PO,from 7th to 20th day of chemotherapy.; Other Names: TSKSR
PLACEBO_COMPARATOR: Placebo group; Placebo of Tonifying Spleen and Kidney Sequential Regimen(TSKSR)similar in color,smell and texture with TSKSR will be prescribed to participants in each course of chemotherapy.	Drug: Placebo of 'Tonifying Spleen and Kidney Sequential Regimen; Placebo of TCM-TSKSR will be given to the participants as follows:placebo of Liu-jun-an-wei Granule,1 pack each time,twice a day,PO,from 0 to 6th day of chemotherapy and placebo of Qi-tu-er-zhi Granule,1 pack each time,twice a day,from 7th to 20th day of chemotherapy.; Other Names: Placebo of TSKSR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion Rate of 8-cycle Adjuvant Chemotherapy	Completion Rate of 8-cycle Adjuvant Chemotherapy=number of participants completing 8-cycle adjuvant chemotherapy/number of participants randomized to each group*100%	6months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion Rate of Adjuvant Chemotherapy of Each Participant	Completion Rate of Adjuvant Chemotherapy of Each Participant=number of the last courses of chemotherapy/8*100%	6months
Completion Rate of 4-cycle Adjuvant Chemotherapy	Completion Rate of 4-cycle Adjuvant Chemotherapy=number of participants completing 4-cycle adjuvant chemotherapy/number of participants randomized to each group*100%	3months
Time to Treatment Failure,TTF	TTF is the period from randomization to the earliest day of an event such as withdrawal from protocol treatment for any reasons, patients refusal and loss to follow-up.	6months
Relative Dose Intensity (RDI) of Adjuvant Chemotherapy	Relative dose intensity (RDI) (%) = (actual dose/ initial dose of adjuvant chemotherapy) × 100%	6months
Proportion of Modifications of Time	Proportion of Modifications of Time=number of participants delaying chemotherapy /number of participants randomized to each group*100%.Delay is defined as ≥7days because of adverse event,such as weakness, myelosuppression, gastrointestinal reactions and other toxicity,except for administrative issues related to hospitalization.	6months
Time of Dose Reductions of Adjuvant Chemotherapy for the First Time	It is the period from randomization to when a chemo-induced grade 3-4 granulocytopenia and/or a chemo-induced grade 2 thrombocytopenia is observed in participants for the first time,in which case,the dose of both Oxaliplatin and Capecitabine will be reduced by 25% of planned dosage.	6months
Time of Dose Reductions of Adjuvant Chemotherapy for the Second Time	It is the period from randomization to when a chemo-induced grade 3-4 granulocytopenia and/or a chemo-induced grade 2 thrombocytopenia is observed in participants for the second time,in which case,the dose of both Oxaliplatin and Capecitabine will be reduced by 50% of planned dosage.	6months
Proportion of Salvage Treatment	Proportion of Salvage Treatment=Number of participants receiving salvage treatment/Number of participants randomized to each group*100%.	6months
Incidence of a Chemo-induced Grade 3-4 Nausea/Vomiting		6 months
Incidence of a Chemo-induced Grade 2 Diarrhea		6 months
Changes of Participants' ESAS Score	Edmonton Symptom Assessment Scale(ESAS) score will be used to evaluate the change of participants' QoL during adjuvant chemotherapy.ESAS has 9 items designed to assess the severity of commonly reported symptoms experienced by cancer patients,including pain, fatigue, drowsiness, nausea, dyspnea, depression, anxiety, well-being, and loss of appetite.Each items ranges from 0 to 10.	6 months
Changes of Participants' FACT-C Score	Functional Assessment of Cancer Therapy-Colorectal (FACT-C) score will be used to evaluate the change of participants' QoL during adjuvant chemotherapy.The FACT-C consists of 36 items,in four domains of well-being (physical,emotional,social,and functional),on a scale of 0 to 4.	6months
Changes of TCM Symptoms Score	Based on a prior expert consensus,11 TCM symptoms were considered to be the most common symptoms during CapeOX chemotherapy,including vomiting, numbness, diarrhea, constipation, sensation of chill, nocturia, forgetfulness, spontaneous sweating, night sweats, dry mouth and canker sores, each of which ranges from 0 to 10.	6months
Changes of Spleen Deficiency Scale Score	Based on prior researches,the investigator designed Spleen Deficiency Scale,which includes 8 items involving appetite,abdominal distension and so on.Each question ranges from 1 to 5.	6months
Changes of Kidney Deficiency Scale Score	Based on prior researches,the investigator designed Kidney Deficiency Scale, which includes 8 items involving soreness of waist, tinnitus, and so on. Each question ranged from 1 to 5.	6months
Incidence of AEs	Adverse effects(AEs) includes abnormal results of blood/urine/stool routine examination, liver/renal function test and electrocardiograms.	6months
Incidence of SAEs	Serious Adverse effects(SAEs) includes abnormal results of blood/urine/stool routine examination, liver/renal function test and electrocardiograms.	6months

Collaborators and Investigators

• Sponsor: Xiyuan Hospital of China Academy of Chinese Medical Sciences
• Collaborators: Jiangsu Province Hospital of Traditional Chinese Medicine; Chongqing University Cancer Hospital; Guangdong Provincial Hospital of Traditional Chinese Medicine; Shanghai Zhongshan Hospital; Peking University Third Hospital; Peking University Cancer Hospital & Institute; Beijing Chao Yang Hospital; Henan Provincial People's Hospital; Tianjin Union Medical Center; Beijing University of Chinese Medicine; Civil Aviation General Hospital; Zhengzhou Hospital of Traditional Chinese Medicine
• Investigators: Principal Investigator: Yufei Yang, M.D., Xi-Yuan Hospital, China Academy of Chinese Medical Sciences

Publications and helpful links

General Publications

• Zhang T, Fei YT, Xu Y, Sun LY, He B, Yan SH, Tang M, Yan YZ, Mao J, Yang YF. Effect of Jianpi Bushen Sequential Formula on Adjuvant Chemotherapy of Colon Cancer: Study Protocol for a Randomized Controlled Trial. Chin J Integr Med. 2021 Dec;27(12):891-895. doi: 10.1007/s11655-021-3448-9. Epub 2021 Aug 25.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 12, 2018
• Primary Completion (ANTICIPATED): May 31, 2021
• Study Completion (ANTICIPATED): May 31, 2021

Study Registration Dates

• First Submitted: October 14, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (ACTUAL): October 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 9, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Chemotherapy; Traditional Chinese Medicine; Colon Cancer; Adverse Effect of Chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: 2017YFC1700604

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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