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Infliximab or Vedolizumab in Treating Immune Checkpoint Inhibitor-Related Colitis in Patients With Genitourinary Cancer or Melanoma

Primary Purpose

Colitis, Lung Non-Small Cell Carcinoma, Malignant Genitourinary System Neoplasm

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Infliximab

Vedolizumab

About this trial

This is an interventional treatment trial for Colitis

Eligibility Criteria

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

Inclusion Criteria:

Patients who receive any type of immune checkpoint inhibitor (ICI) therapy
Patients with peak grade >= 2 immune-related diarrhea and/or colitis (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 within 45 days prior to initiation of study treatment (infliximab/ vedolizumab)
Patients with ability to understand and willingness to sign informed consent
Patients with genitourinary cancer or melanoma or non-small cell lung cancer
No concern for active concomitant GI infection for immune-related diarrhea and/or colitis work up at the time of protocol therapy initiation as confirmed by stool tests or as per the treating physician based on clinical presentation
Patient who has been cleared for enrollment by Infectious Diseases consultant or treating physician if positive infection workup or screening tests (e.g. lifelong positive T-spot due to BCG inoculation, chronic colonization) prior to initiation of diarrhea/colitis treatment

Exclusion Criteria:

Patients younger than 18 years of age
Patients with persistent gastrointestinal infection confirmed with positive testing despite completing 5 days of antibiotics
Patients are on concurrent immunosuppressive therapies other than what will be given for colitis
Patients with preexisting activehistory of inflammatory bowel disease and/or radiation enterocolitis with active disease status at the time of study treatment initiation
Pregnant and breastfeeding women, and
Women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test unless last menstrual cycle was > 1 year prior to consent and/ or clear documentation states that patient is peri- or post-menopausal or there was recent supporting objective evidence of 'no pregnancy' status (e.g. blood or imaging) within 30 days prior to initiation of study treatment
Patients who develop concurrent non-GI toxicity at the time of study treatment initiation

Sites / Locations

M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I (infliximab)

Arm II (vedolizumab)

Arm Description

Patients receive infliximab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Patients receive vedolizumab IV over 1 hour at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Clinical remission/response rate of immune-mediated colitis (IMC)

The difference of the remission rate between standard of care (infliximab + corticosteroid) and the treatment with vedolizumab + corticosteroid will be calculated along with the 95% confidence interval.

Treatment-related adverse events

Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.

Secondary Outcome Measures

Clinical remission/response rate of IMC

Will be estimated and compared between the two treatment arms using chi-square test.

Complete weaning of corticosteroid

Will be estimated and compared between the two treatment arms using chi-square test.

Recurrent immune-related diarrhea/colitis

Will be estimated and compared between the two treatment arms using chi-square test.

Full Information

NCT ID

NCT04407247

First Posted

May 27, 2020

Last Updated

October 5, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04407247

Brief Title

Infliximab or Vedolizumab in Treating Immune Checkpoint Inhibitor-Related Colitis in Patients With Genitourinary Cancer or Melanoma

Official Title

Treatment of Immune Checkpoint Inhibitor-Related Colitis With Infliximab or Vedolizumab: A Randomized Trial

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 9, 2020 (Actual)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This phase I/II trial studies the side effects of infliximab and vedolizumab and to see how well they work in treating inflammation of the colon (colitis) caused by immune checkpoint inhibitor therapy in patients with cancer of the genital and urinary organs (genitourinary) or melanoma. Monoclonal antibodies, such as infliximab or vedolizumab, may help to treat immunotherapy induced colitis/diarrhea. This study may help to identify the optimal treatment strategy for immune checkpoint inhibitor-related colitis in patients with genitourinary cancer or melanoma.

Detailed Description

PRIMARY OBJECTIVES: I. To compare the efficacy of infliximab and vedolizumab for clinical remission/response of immune-related diarrhea and/or colitis. II. To assess the safety and tolerability of the treatment for immune-mediated diarrhea and/or colitis. SECONDARY OBJECTIVES: I. To assess the efficacy of infliximab and vedolizumab for clinical remission/response of IMC at 4 weeks. II. To assess the success of corticosteroid tapering. III. To measure the recurrence rate after corticosteroid taper. EXPLORATORY OBJECTIVES: I. To assess the efficacy of infliximab and vedolizumab to achieve endoscopic remission of immune-related diarrhea and/or colitis. II. To assess the efficacy of infliximab and vedolizumab to achieve histological remission of immune-related diarrhea and/or colitis. III. To assess the time duration to achieve the clinical remission/response. IV. To assess the long term outcome of cancer. V. To assess immunological, molecular and microbiome changes in tissue/blood/stool. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive infliximab intravenously (IV) over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive vedolizumab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity. Patients are followed up weekly for 1 month and then at 2 and 3 months after the treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colitis, Lung Non-Small Cell Carcinoma, Malignant Genitourinary System Neoplasm, Malignant Solid Neoplasm, Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm I (infliximab)

Arm Type

Active Comparator

Arm Description

Patients receive infliximab IV over 1 hour once at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Arm Title

Arm II (vedolizumab)

Arm Type

Experimental

Arm Description

Patients receive vedolizumab IV over 1 hour at week 0, 2, 6 for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

Intervention Type

Biological

Intervention Name(s)

Infliximab

Other Intervention Name(s)

Avakine, cA2, Remicade, Remsima

Intervention Description

Given IV

Intervention Type

Biological

Intervention Name(s)

Vedolizumab

Other Intervention Name(s)

Entyvio, Immunoglobulin G1, anti-(human integrin LPAM-1 (lymphocyte Peyer''s patch adhesion molecule 1)) (human-Mus musculus heavy chain), disulfide with human-Mus musculus kappa-chain, dimer, LDP 02, LDP-02, LDP02, MLN0002, MLN02

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Clinical remission/response rate of immune-mediated colitis (IMC)

Description

Time Frame

At 2 weeks after initiation of infliximab or vedolizumab with corticosteroid taper

Title

Treatment-related adverse events

Description

Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.

Time Frame

Within 3 months after initiation of infliximab or vedolizumab

Secondary Outcome Measure Information:

Title

Clinical remission/response rate of IMC

Description

Will be estimated and compared between the two treatment arms using chi-square test.

Time Frame

At 4 weeks after initiation of infliximab or vedolizumab with corticosteroid taper

Title

Complete weaning of corticosteroid

Description

Will be estimated and compared between the two treatment arms using chi-square test.

Time Frame

Within 4 weeks after infliximab or vedolizumab initiation without rebound of IMC

Title

Recurrent immune-related diarrhea/colitis

Description

Will be estimated and compared between the two treatment arms using chi-square test.

Time Frame

Within 3 months after corticosteroid taper

Other Pre-specified Outcome Measures:

Title

Endoscopic remission (Mayo Clinic sub-score 0-1) of immune-related diarrhea/colitis

Description

Will be compared between the two treatment arms.

Time Frame

At 4 and 8 weeks after initiation of infliximab or vedolizumab treatment

Title

Histological remission (resolution of active inflammation) of immune-related diarrhea/colitis

Description

Will be compared between the two treatment arms.

Time Frame

At 8 weeks after initiation of infliximab or vedolizumab treatment

Title

Time duration to achieve clinical remission/response

Description

Will be estimated using the method of Kaplan and Meier. Comparisons of the time-to-event endpoint by important subgroups will be made using the log-rank tests.

Time Frame

From initiation of infliximab or vedolizumab treatment to clinical remission/response or last follow-up, assessed up to 3 months

Title

Overall survival

Description

Will be estimated using the method of Kaplan and Meier.

Time Frame

From the initiation of infliximab or vedolizumab treatment till death or last follow-up, assessed up to 3 months

Title

Change in levels of cytokines in tissue/blood/stool samples

Description

Will be compared using 2-sample t-test.

Time Frame

Baseline up to 3 months after infliximab or vedolizumab treatment

Title

Change in frequencies of immune cells in tissue/blood/stool samples

Description

Will be compared using 2-sample t-test.

Time Frame

Baseline up to 3 months after infliximab or vedolizumab treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients who receive any type of immune checkpoint inhibitor (ICI) therapy Patients with peak grade >= 2 immune-related diarrhea and/or colitis (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 within 45 days prior to initiation of study treatment (infliximab/ vedolizumab) Patients with ability to understand and willingness to sign informed consent Patients with genitourinary cancer or melanoma or non-small cell lung cancer No concern for active concomitant GI infection for immune-related diarrhea and/or colitis work up at the time of protocol therapy initiation as confirmed by stool tests or as per the treating physician based on clinical presentation Patient who has been cleared for enrollment by Infectious Diseases consultant or treating physician if positive infection workup or screening tests (e.g. lifelong positive T-spot due to BCG inoculation, chronic colonization) prior to initiation of diarrhea/colitis treatment Exclusion Criteria: Patients younger than 18 years of age Patients with persistent gastrointestinal infection confirmed with positive testing despite completing 5 days of antibiotics Patients are on concurrent immunosuppressive therapies other than what will be given for colitis Patients with preexisting activehistory of inflammatory bowel disease and/or radiation enterocolitis with active disease status at the time of study treatment initiation Pregnant and breastfeeding women, and Women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test unless last menstrual cycle was > 1 year prior to consent and/ or clear documentation states that patient is peri- or post-menopausal or there was recent supporting objective evidence of 'no pregnancy' status (e.g. blood or imaging) within 30 days prior to initiation of study treatment Patients who develop concurrent non-GI toxicity at the time of study treatment initiation

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yinghong Wang

Phone

713-792-7672

ywang59@mdanderson.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yinghong Wang

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yinghong Wang

Phone

713-792-7672

First Name & Middle Initial & Last Name & Degree

Yinghong Wang

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center

Learn more about this trial

Infliximab or Vedolizumab in Treating Immune Checkpoint Inhibitor-Related Colitis in Patients With Genitourinary Cancer or Melanoma

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