Clinical trial NCT04736186: Prevention and Treatment of Pyrrolitinib-associated Diarrhea
Official title: Prevention and Treatment of Pyrrolitinib-associated Diarrhea: a Prospective, Multicenter, Open-label Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Breast Cancer
Keywords: Diarrhea
Non-secondary prevention
Secondary prevention
pyrrolitinib
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2021-02-03
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non-secondary prevention: Explore the recovery time of oral loperamide 4mg T.I.D. for pyrrolitinib induced diarrhea of 1-2 degrees.

Secondary prevention: To explore the incidence of grade 3 and above diarrhea during c1D1-C1D22 in patients with oral loperamide 4 mg, T.I.D. (D1-7) →4 mg, B.I.D. (D8-21).
Primary purpose: PREVENTION

Brief summary: In this study, patients taking pyrrolitinib alone or combined with pyrrolitinib were recruited (170 cases of secondary prevention and 300 cases of non-secondary prevention).

Non-secondary prevention: Explore the recovery time of oral loperamide 4mg T.I.D. for pyrrolitinib induced diarrhea of 1-2 degrees.

Secondary prevention: To explore the incidence of grade 3 and above diarrhea during c1D1-C1D22 in patients with oral loperamide 4 mg, T.I.D. (D1-7) →4 mg, B.I.D. (D8-21).

Detailed description: The study can only be formally carried out with the written approval of the ethics committee. Investigators regularly submit annual research reports to the ethics committee. Investigators will inform the ethics committee in writing when the study is discontinued and / or completed.

All patients were required to sign informed consent before entering the group. All updated versions of informed consent and written information will be provided to the subjects during the participant's participation.

In the experimental design stage, the statistical principle was used to make reasonable and effective arrangements for the relevant factors. Employ statistical experts to calculate the sample size and data statistics, and participate in the design process. Data collection and follow-up were conducted by specially assigned personnel, professional doctors were assigned to conduct data review regularly, and special data management personnel were provided. They will ensure the authenticity, reliability and security of data throughout the process.

Eligibility criteria: Inclusion Criteria:

1. One of the following two situations:

   A) Plan to take pyrrolitinib for ≥21 days; B) Third-degree diarrhea or second-degree diarrhea with complications after taking pyrrolitinib at present, plan to take pyrrolitinib for ≥21 days;
2. Age ≥18 years;
3. ECOG PS 0-2;
4. Life expectancy ≥6 months;
5. Participate in this study voluntarily, sign informed consent, have good compliance and are willing to cooperate with the follow-up.

Exclusion Criteria:

1. May be allergic to pyrrolitinib or excipients;
2. There are many factors affecting the absorption of oral drugs, such as inability to swallow, nausea and vomiting;
3. Patients with biliary obstruction;
4. Participate in other diarrhea-related clinical trials;
5. Pregnant and lactating women, fertile women who tested positive in the baseline pregnancy test, or women of childbearing age who were unwilling to use effective contraception during the whole trial period;
6. Concomitant diseases (including but not limited to severe hypertension beyond the control of drugs, severe diabetes, etc.) that, according to the judgment of the researcher, seriously endanger the safety of the patient or affect the completion of the study; The investigator concluded that the patient was not eligible for any of the other conditions in the study.

Primary outcomes:
measure: time from the first day of treatment until diarrhea returns to level 0 or baseline during the first day of treatment to the 22nd day of treatment
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The proportion of 3/4 degree diarrhea in group A From the first day of treatment to the 22nd day of treatment
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
Secondary outcomes:
measure: Loperamide combined program, diarrhea recovery to level 0 or baseline time
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: 3/4 degree incidence of diarrhea
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The accumulated time of diarrhea during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: Time of first occurrence of diarrhea
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The incidence rate of all degrees of diarrhea during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The incidence of constipation of degree 2 or above during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: Other AE/SAE during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The proportion of cases with 3/4 degree diarrhea
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The proportion of incidences of 3/4 degree diarrhea during follow-up
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The incidence rate of all degrees of diarrhea during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The incidence of constipation of degree 2 or above during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The time of the first diarrhea attack during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: The cumulative duration of diarrhea during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: Proportion of subjects with delayed or reduced doses of pyrrolitinib due to diarrhea
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: Other AE/SAE during the follow-up period
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
Other outcomes:
measure: Risk factor analysis for diarrhea（The baseline information, demographic data, past treatment history, treatment plan and diet habits of patients with diarrhea were summarized, and the risk factors of diarrhea were summarized）
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: Analysis of intestinal flora（During the experiment, the feces were collected three times for microbiological examination, and the results of microbiological examination were summarized and analyzed to understand the types of microbiota）
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
measure: Efficacy of pyrrolitinib (According to the curative effect evaluation standard of solid tumor version 1.1, the imaging curative effect of tumor was evaluated）
timeFrame: From the first day of treatment to the 22nd day of treatment(about 21 days)
Locations:
city: Tianjin
country: China
facility: TianJin Medical University Cancer Institute and Hospital
Study officials:
References: