A Study Evaluating Bacillus Cereus in the Prevention of Afatinib-associated Diarrhea

A Single-arm, Single-institutional, Phase II Study Evaluating the Efficacy and Safety of Bacillus Cereus (Changfukang®) in the Prevention of Afatinib-associated Diarrhea in NSCLC Patients

Afatinib is an irreversible ErbB-family blocker with approved clinical activity in non-small-cell lung cancer (NSCLC) with EGFR mutations. It has received regulatory approval for use as a treatment for patients with lung adenocarcinoma whose tumors harbour activating EGFR mutations within exons 18-21 of the EGFR receptor, or patients with lung squamous cell carcinoma whose disease progress after platinum-based doublet chemotherapy. However, diarrhea is the most commonly reported adverse events associated with afatinib treatment (> 90%). Although these events are generally mild to moderate in severity, diarrhea adversely affects the tolerability of cancer treatment, and in severe cases diarrhea has the potential to affect the efficacy of treatment due to poor compliance, or treatment interruption, or dosage reduction. Currently, no prophylactic measure was demonstrated efficaciously. Bacillus cereus is an aerobic spore-forming bacterium that is commonly found in soil. The efficacy of Bacillus cereus in the management of afatinib treatment-associated diarrhoea has not been extensively evaluated in clinical studies. This is a single-arm, single-institutional, phase II study evaluating the efficacy and safety of Bacillus cereus (Changfukang®) in the prevention of afatinib-associated diarrhea in NSCLC patients.

Study Overview

• Status: Terminated
• Conditions: Diarrhea; Treatment Side Effects
• Intervention / Treatment: Drug: Bacillus Cereus tablets

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed locally advanced or metastastic non-small-cell lung cancer
• Suitable for the treatment of afatinib assessed by investigator
• Age >=18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy of at least 12 weeks
• Able to swallow and retain oral medications
• Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, ie, intrauterine device, bilateral tubal ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle of the patient), from the time of informed consent until 28 days after the last dose of the investigational products. Men and their female partners of childbearing potential must agree and commit to use a highly effective method of contraception (ie, any of the above methods or hormonal contraception associated with inhibition of ovulation) while on treatment and for 3 months after last dose of investigational products
• Provide written, informed consent to participate in the study and follow the study procedures

• Patient has adequate bone marrow as defined by the following laboratory values:

  • White blood cell ≥ 3.0 × 109/L
  • Absolute neutrophil count ≥ 1.5 × 109/L
  • Platelets ≥ 75 × 109/L

• Patient has adequate organ function as defined by the following laboratory values:

  • In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver metastases, ALT and AST should be < 5 × ULN
  • Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range of the central laboratory in patients with well documented
  • Gilbert's Syndrome
  • Serum creatinine ≤ 1.5 × ULN

Exclusion Criteria:

• Previous treatment with EGFR-TKI or anti-EGFR antibody
• History of gastrointestinal disease with diarrhea as the primary symptom in the last three months.
• Another malignancy within 3 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
• Diagnosed as having CNS metastases, except those whose CNS disease were stable and dehydration treatment were unrequired within 4 weeks prior to the first dose of afatinib
• Any severe and / or uncontrolled medical conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Changfukang® group; Patients in Changfukang group will receive Changfukang® (Bacillus Cereus tablets).	Drug: Bacillus Cereus tablets; Bacillus Cereus tablets was taken two tablets three times a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diarrhoea rate of all grades	Proportion of subjects experiencing diarrhoea of all grades, as defined by the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 4.03, recorded as AEs in the Electronic case report form (eCRF)	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diarrhoea rate of grade 2 and above	Proportion of subjects experiencing diarrhoea of grade 2 and above, as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF	Up to 4 weeks
Diarrhoea rate of grade 3 and above	Proportion of subjects experiencing diarrhoea of grade 3 and above, as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF	Up to 4 weeks
Days of diarrhoea of all grades	Number of days of subjects experiencing diarrhoea of all grades, as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF	Up to 4 weeks
Days of diarrhoea of grade 2 and above	Number of days of subjects experiencing diarrhoea of grade 2 and above, as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF	Up to 4 weeks
Days of diarrhoea of grade 3 and above	Number of days of subjects experiencing diarrhoea of grade 3 and above, as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF	Up to 4 weeks
Proportion of subjects taking anti-diarrheal medication	Proportion of subjects taking anti-diarrhoeal medication as recorded in the eCRF	Up to 4 weeks
Proportion of subjects with AEs and SAEs	Proportion of subjects with AEs and SAEs were assessed from the start of the study until end of study as recorded in the eCRF	Up to 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall response rate as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks
Clinical Benefit Response	Clinical benefit response as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks
Progression-free Survival	Progression-free Survival as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2018
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: March 18, 2018
• First Submitted That Met QC Criteria: March 31, 2018
• First Posted (Actual): April 3, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: NSCLC; diarrhea; afatinib; Bacillus Cereus
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: 2017-FXY-137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes