Prevention and Treatment of Pyrrolitinib-associated Diarrhea

Prevention and Treatment of Pyrrolitinib-associated Diarrhea: a Prospective, Multicenter, Open-label Clinical Study

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).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Loperamide; Drug: Loperamide and golden bifid; Drug: Loperamide and montmorillonite powder

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.

• Study Type: Interventional
• Enrollment (Anticipated): 470
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Tianjin, China, 300060
    • Recruiting
    • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Loperamide; Loperamide 4 mg, T.I.D. (D1-7) →4 mg, B.I.D. (D8-21)	Drug: Loperamide; Loperamide 4 mg， t.i.d.(d 1-7);4 mg, b.i.d.(d 8-21)
EXPERIMENTAL: Loperamide and gold bifid; Loperamide 4 mg, T.I.D. (D1-7) →4 mg, B.I.D. (D8-21) + gold bifid2g T.I.D.	Drug: Loperamide; Loperamide 4 mg， t.i.d.(d 1-7);4 mg, b.i.d.(d 8-21); Drug: Loperamide and golden bifid; Patients with secondary prevention will be randomly assigned to B：Loperamide 4 mg， t.i.d.(d 1-7);4 mg, b.i.d.(d 8-21)+golden bifid 2 g t.i.d.
EXPERIMENTAL: Loperamide and Montmorillonite SAN; Loperamide 4 mg, T.I.D. (D1-7) →4 mg, B.I.D. (D8-21) + Montmorillonite SAN 3 g, T.I.D.	Drug: Loperamide; Loperamide 4 mg， t.i.d.(d 1-7);4 mg, b.i.d.(d 8-21); Drug: Loperamide and montmorillonite powder; Patients with secondary prevention will be randomly assigned to D：Loperamide 4 mg， t.i.d.(d 1-7);4 mg, b.i.d.(d 8-21)+montmorillonite powder 3 g t.i.d.
NO_INTERVENTION: Non-intervention; Do not intervene and stop diarrhea as needed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Non-secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The proportion of 3/4 degree diarrhea in group A From the first day of treatment to the 22nd day of treatment	Secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loperamide combined program, diarrhea recovery to level 0 or baseline time	Non-secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
3/4 degree incidence of diarrhea	Non-secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The accumulated time of diarrhea during the follow-up period	Non-secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
Time of first occurrence of diarrhea	Non-secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The incidence rate of all degrees of diarrhea during the follow-up period	Non-secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The incidence of constipation of degree 2 or above during the follow-up period	Non-secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
Other AE/SAE during the follow-up period	Non-secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The proportion of cases with 3/4 degree diarrhea	secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The proportion of incidences of 3/4 degree diarrhea during follow-up	secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The incidence rate of all degrees of diarrhea during the follow-up period	secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The incidence of constipation of degree 2 or above during the follow-up period	secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The time of the first diarrhea attack during the follow-up period	secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
The cumulative duration of diarrhea during the follow-up period	secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
Proportion of subjects with delayed or reduced doses of pyrrolitinib due to diarrhea	secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)
Other AE/SAE during the follow-up period	secondary prevention	From the first day of treatment to the 22nd day of treatment(about 21 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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）	exploratory，descriptive results	From the first day of treatment to the 22nd day of treatment(about 21 days)
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）	exploratory，descriptive results	From the first day of treatment to the 22nd day of treatment(about 21 days)
Efficacy of pyrrolitinib (According to the curative effect evaluation standard of solid tumor version 1.1, the imaging curative effect of tumor was evaluated）	exploratory，descriptive results	From the first day of treatment to the 22nd day of treatment(about 21 days)

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 16, 2020
• Primary Completion (ANTICIPATED): October 31, 2022
• Study Completion (ANTICIPATED): April 30, 2023

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (ACTUAL): February 3, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 3, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Diarrhea; Secondary prevention; Non-secondary prevention; pyrrolitinib
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Physiological Effects of Drugs; Gastrointestinal Agents; Protective Agents; Antidotes; Loperamide; Antidiarrheals; Bentonite
• Other Study ID Numbers: YWBC-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No