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

• ClinicalTrials.gov Identifier: NCT03486587
• Recruitment Status: Terminated
• First Posted: April 3, 2018
• Last Update Posted: October 4, 2021
• Sponsor: Sun Yat-sen University
• Information provided by (Responsible Party): Li Zhang, MD, Sun Yat-sen University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Diarrhea; Treatment Side Effects	Drug: Bacillus Cereus tablets	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: a single-arm, single-institutional, phase II study
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: April 15, 2018
• Actual Primary Completion Date: August 31, 2020
• Actual Study Completion Date: December 31, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Diarrhoea rate of all grades [ Time Frame: Up to 4 weeks ]
   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)

Secondary Outcome Measures :

1. Diarrhoea rate of grade 2 and above [ Time Frame: Up to 4 weeks ]
   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
2. Diarrhoea rate of grade 3 and above [ Time Frame: Up to 4 weeks ]
   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
3. Days of diarrhoea of all grades [ Time Frame: Up to 4 weeks ]
   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
4. Days of diarrhoea of grade 2 and above [ Time Frame: Up to 4 weeks ]
   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
5. Days of diarrhoea of grade 3 and above [ Time Frame: Up to 4 weeks ]
   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
6. Proportion of subjects taking anti-diarrheal medication [ Time Frame: Up to 4 weeks ]
   Proportion of subjects taking anti-diarrhoeal medication as recorded in the eCRF
7. Proportion of subjects with AEs and SAEs [ Time Frame: Up to 4 weeks ]
   Proportion of subjects with AEs and SAEs were assessed from the start of the study until end of study as recorded in the eCRF

Other Outcome Measures:

1. Overall Response Rate [ Time Frame: Up to 4 weeks ]
   Overall response rate as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
2. Clinical Benefit Response [ Time Frame: Up to 4 weeks ]
   Clinical benefit response as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
3. Progression-free Survival [ Time Frame: Up to 4 weeks ]
   Progression-free Survival as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

China, Guangdong

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China, 510060

Sponsors and Collaborators

Sun Yat-sen University

Investigators

• Principal Investigator: Li Zhang, MD; Sun Yat-sen University

More Information

• Responsible Party: Li Zhang, MD, Professor, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT03486587
• Other Study ID Numbers: 2017-FXY-137
• First Posted: April 3, 2018
• Last Update Posted: October 4, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Keywords provided by Li Zhang, MD, Sun Yat-sen University:

afatinib; diarrhea; Bacillus Cereus; NSCLC

Additional relevant MeSH terms:

Diarrhea; Signs and Symptoms, Digestive