Clinical trial NCT06596343: Evaluating the Benefits of Personalized Traditional Chinese Medicine in Postoperative Treatment for Locally Advanced Colorectal Cancer
Official title: Study on the Value of Traditional Chinese Medicine Precision Treatment Based on Syndrome Differentiation in Postoperative Adjuvant Therapy for Locally Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Colorectal Cancer
Postoperative Adjuvant Therapy
Lead sponsor: Sir Run Run Shaw Hospital
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to explore the role of Traditional Chinese Medicine (TCM) based on syndrome differentiation in reducing chemotherapy side effects, lowering the risk of metastasis and recurrence, and improving survival rates in postoperative colorectal cancer patients through a prospective, single-arm interventional clinical trial.

Detailed description: Colorectal cancer is the third leading cause of cancer-related deaths worldwide, with 1.9 million new cases and nearly 935,000 deaths reported in 2020. In China, colorectal cancer ranks third in new cases for both men and women, while it ranks fifth in cancer-related deaths among men and second among women. It has become a global public health issue and a major threat to people's health. Surgical resection is the primary treatment for colon cancer and can potentially cure the tumor. More than 50% of colon cancer patients are diagnosed at locally advanced stages (stage II and III). Even after curative surgery, about 50% of these patients experience tumor recurrence due to undetectable micrometastases that persist post-surgery. Most of these patients require adjuvant chemotherapy to eliminate micrometastases and improve cure rates. Postoperative adjuvant chemotherapy can eradicate hidden micrometastases and prolong survival in colorectal cancer patients. Large clinical trials have shown that adjuvant chemotherapy reduces the recurrence rate by 41% and overall mortality by 33%. Thus, surgery combined with postoperative adjuvant chemotherapy is the standard treatment approach to cure colon cancer.

However, about 25% of stage III colorectal cancer patients still relapse despite adjuvant chemotherapy, indicating that not all patients benefit from it. Additionally, postoperative adjuvant chemotherapy can cause numerous side effects. The IDEA study reported that grade 3 or higher chemotherapy-related toxicities occurred in 20% of patients receiving 3 months of adjuvant chemotherapy and 36.9% of patients receiving 6 months. These side effects include mucositis, vomiting, diarrhea, febrile neutropenia, fatigue, hair loss, hand-foot syndrome (pain, redness, and peeling of the skin on the palms and soles), neurotoxicity, and cardiotoxicity. The incidence and severity of these side effects vary depending on the specific drugs and administration methods, and some side effects, such as oxaliplatin-induced peripheral neuropathy, can persist long-term, significantly affecting patients' quality of life.

Thus, both healthcare providers and patients are seeking additional therapies to reduce toxicity and improve the efficacy of standard treatment. In real-world practice, many colorectal cancer patients have received Traditional Chinese Medicine (TCM) as part of their postoperative care, and TCM plays a significant role in colorectal cancer prevention and treatment.

In TCM, colorectal cancer is classified under conditions such as "zang du" (organ toxin), "chang ji" (intestinal accumulation), and "ji ju" (mass accumulation), primarily caused by irregular diet, emotional imbalance, and deficiency of vital energy (qi). Although the disease originates in the intestines, it is closely related to the spleen, stomach, liver, and kidneys. Early-stage disease is dominated by damp-heat and toxin stagnation, while later stages are characterized by a deficiency of vital energy with excess pathogenic factors, typically involving spleen and kidney yang deficiency, qi and blood deficiency, or liver and kidney yin deficiency. A deficiency in vital energy and yin-yang imbalance are key factors in the development of colorectal cancer. Damp-heat accumulation in the intestines leads to stagnation of qi, toxin formation, and eventual mass formation, which is a core mechanism of disease development.

This study aims to investigate the role of adding TCM during and after surgery and chemotherapy to enhance the clinical efficacy of adjuvant chemotherapy, reduce the occurrence of adverse effects, prevent metastasis and recurrence, and ultimately improve survival rates.

Eligibility criteria: Inclusion Criteria:

* 1. Age between 18 and 75 years. 2. Diagnosed with colorectal cancer at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and underwent standard radical colorectal cancer surgery. Postoperative pathological staging is stage III (AJCC 8th edition: T4, any N+, M0, or any T, N2, M0), indicating the need for chemotherapy according to the CSCO 2023 colorectal cancer guidelines.

  3. Willing to receive Traditional Chinese Medicine (TCM) treatment. 4. Voluntarily agree to participate in the study and sign the informed consent form. If the subject is unable to read or sign the consent due to incapacity, the informed consent must be obtained from a legal guardian. If the subject cannot read the consent (e.g., illiterate subjects), a witness must observe and sign the consent process.

  5. Expected survival of ≥12 months. 6. ECOG performance status score of 0-1. 7. No prior anti-cancer, immunotherapy, or radiation treatment. 8. Laboratory tests meeting the following criteria:
* White blood cell count ≥3.5 × 10\^9/L, absolute neutrophil count ≥1.8 × 10\^9/L, platelet count ≥100 × 10\^9/L, hemoglobin ≥100 g/L.
* INR ≤1.5 and APTT ≤1.5 times the upper limit of normal (ULN) or PTT ≤1.5 times ULN.
* Total bilirubin ≤1.25 times ULN; ALT and AST ≤3 times ULN; serum albumin ≥28 g/L.
* 24-hour creatinine clearance rate ≥50 mL/min or serum creatinine ≤1.5 times ULN.

Exclusion Criteria:

* 1. Colorectal cancer patients with distant metastasis as indicated by preoperative evaluation.

  2. Postoperative pathological results indicate that chemotherapy is not required according to the CSCO 2023 colorectal cancer guidelines.

  3. Patients who have received neoadjuvant chemoradiotherapy before surgery. 4. Patients with severe heart, liver, kidney damage, or bone marrow dysfunction.

  5. Pregnant or breastfeeding women. 6. Patients with known allergies to Traditional Chinese Medicine components. 7. Patients who refuse chemotherapy or TCM treatment. 8. Patients with a history of mental illness or cognitive impairment.

Primary outcomes:
measure: The incidence of grade III/IV adverse events
timeFrame: From the beginning of the first chemotherapy to three months after the end of the course of chemotherapy
Secondary outcomes:
measure: 3-year Disease-Free Survival
timeFrame: 3 years post-treatment
measure: 3-year Overall Survival
timeFrame: 3 years post-treatment
measure: Completion rate of adjuvant chemotherapy
timeFrame: From the beginning of the first chemotherapy to the end of the course of chemotherapy, up to 6 months.
measure: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30
timeFrame: From the beginning of the first chemotherapy to three months after the end of the course of chemotherapy
measure: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module （EORTC QLQ-CR29）
timeFrame: From the beginning of the first chemotherapy to three months after the end of the course of chemotherapy
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University
Study officials:
References:
citation: Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. doi: 10.1056/NEJMoa1713709.
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citation: Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023 May-Jun;73(3):233-254. doi: 10.3322/caac.21772. Epub 2023 Mar 1.