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

Primary Purpose

Diarrhea, Treatment Side Effects

Status
Terminated
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Bacillus Cereus tablets
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diarrhea focused on measuring afatinib, diarrhea, Bacillus Cereus, NSCLC

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sun Yat-sen University Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Changfukang® group

Arm Description

Patients in Changfukang group will receive Changfukang® (Bacillus Cereus tablets).

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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
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
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
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
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
Proportion of subjects taking anti-diarrheal medication
Proportion of subjects taking anti-diarrhoeal medication as recorded in the eCRF
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

Full Information

First Posted
March 18, 2018
Last Updated
September 27, 2021
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT03486587
Brief Title
A Study Evaluating Bacillus Cereus in the Prevention of Afatinib-associated Diarrhea
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Terminated
Why Stopped
Participants have better treatment selection, resulting in a slow recruitment.
Study Start Date
April 15, 2018 (Actual)
Primary Completion Date
August 31, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diarrhea, Treatment Side Effects
Keywords
afatinib, diarrhea, Bacillus Cereus, NSCLC

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
a single-arm, single-institutional, phase II study
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Changfukang® group
Arm Type
Experimental
Arm Description
Patients in Changfukang group will receive Changfukang® (Bacillus Cereus tablets).
Intervention Type
Drug
Intervention Name(s)
Bacillus Cereus tablets
Intervention Description
Bacillus Cereus tablets was taken two tablets three times a day.
Primary Outcome Measure Information:
Title
Diarrhoea rate of all grades
Description
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)
Time Frame
Up to 4 weeks
Secondary Outcome Measure Information:
Title
Diarrhoea rate of grade 2 and above
Description
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
Time Frame
Up to 4 weeks
Title
Diarrhoea rate of grade 3 and above
Description
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
Time Frame
Up to 4 weeks
Title
Days of diarrhoea of all grades
Description
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
Time Frame
Up to 4 weeks
Title
Days of diarrhoea of grade 2 and above
Description
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
Time Frame
Up to 4 weeks
Title
Days of diarrhoea of grade 3 and above
Description
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
Time Frame
Up to 4 weeks
Title
Proportion of subjects taking anti-diarrheal medication
Description
Proportion of subjects taking anti-diarrhoeal medication as recorded in the eCRF
Time Frame
Up to 4 weeks
Title
Proportion of subjects with AEs and SAEs
Description
Proportion of subjects with AEs and SAEs were assessed from the start of the study until end of study as recorded in the eCRF
Time Frame
Up to 4 weeks
Other Pre-specified Outcome Measures:
Title
Overall Response Rate
Description
Overall response rate as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Time Frame
Up to 4 weeks
Title
Clinical Benefit Response
Description
Clinical benefit response as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Time Frame
Up to 4 weeks
Title
Progression-free Survival
Description
Progression-free Survival as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Time Frame
Up to 4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Li Zhang, MD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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