Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Infliximab for Treatment of Ipilimumab Colitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04305145
Recruitment Status : Not yet recruiting
First Posted : March 12, 2020
Last Update Posted : March 12, 2020
Sponsor:
Information provided by (Responsible Party):
Michael Dougan, Massachusetts General Hospital

Brief Summary:
This research study is evaluating the effectiveness and safety of infliximab therapy compared with steroids in the treatment of ipilimumab-induced colitis in patients with III/IV melanoma.

Condition or disease Intervention/treatment Phase
Melanoma Stage III Melanoma Stage IV Side Effect of Drug Colitis Drug: Infliximab Drug: Methylprednisolone Drug: Prednisone Phase 2

Detailed Description:

This is a phase II, randomized, signal-detection trial to evaluate the efficacy and safety of the drugs Infliximab, Methylprednisolone and prednisone to manage the side of effect of colitis from the standard of care drug ipilimumab

The names of the study drugs involved in this study are:

  • Infliximab
  • Methylprednisolone
  • Prednisone

Participants will receive ipilimumab and any other cancer treatments per standard of care for stage III/IV melanoma at the discretion of treating oncologist.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Participants are expected to be on study treatment for up to 7 weeks and followed every to 6 months as agreed.

It is expected that about 42 people will take part in this research study.

The FDA has approved infliximab, methylprednisolone, and prednisone as treatment options for colitis.

Patients will also receive ipilimumab as part of the standard of care for stage III/IV melanoma.

The U.S. Food and Drug Administration (FDA) has approved ipilimumab as a treatment option for III/IV melanoma.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Infliximab for the Treatment of Ipilimumab Colitis
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Infliximab

Arm Intervention/treatment
Experimental: Infliximab

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

  • Infliximab: Predetermined intravenous single dose, up to 3 doses over 7 weeks.
  • Cross over for inadequate response -- Patients who do not respond to initial treatment within 3 days with a decrease in symptoms by one grade, or who do not improve to grade 2 or less symptoms by 5 days will add combination therapy from the other treatment arm at full initial dosing
Drug: Infliximab
Infusion
Other Names:
  • AVSOLA
  • Ixifi
  • Remicade
  • Renflexis

Experimental: Inpatient

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

  • methylprednisone-Predetermined intravenous dose, 2x daily up to 7 weeks
  • prednisone Oral daily predetermined dose
  • Cross over for inadequate response -- Patients who do not respond to initial treatment within 3 days with a decrease in symptoms by one grade, or who do not improve to grade 2 or less symptoms by 5 days will add combination therapy from the other treatment arm at full initial dosing
Drug: Methylprednisolone
Infusion
Other Names:
  • Solu-Medrol
  • Duralone
  • Medralone
  • Medrol
  • M-Prednisol

Drug: Prednisone
Orally
Other Names:
  • Deltasone
  • Prednicot
  • predniSONE Intensol
  • Rayos
  • Sterapred
  • Sterapred DS

Experimental: Outpatient

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits

  • Prednisone Predetermined oral dose, 2x daily up to 7 weeks
  • Cross over for inadequate response -- Patients who do not respond to initial treatment within 3 days with a decrease in symptoms by one grade, or who do not improve to grade 2 or less symptoms by 5 days will add combination therapy from the other treatment arm at full initial dosing
Drug: Prednisone
Orally
Other Names:
  • Deltasone
  • Prednicot
  • predniSONE Intensol
  • Rayos
  • Sterapred
  • Sterapred DS




Primary Outcome Measures :
  1. Proportion of patients with Steroid-Free Colitis [ Time Frame: 7 weeks ]
    Proportion of Patients with Steroid-Free Colitis at seven weeks with steroid-free colitis remission defined as less than 7.5 mg a day of prednisone or equivalent and grade-1 or lower symptoms.


Secondary Outcome Measures :
  1. Proportion of Participants with Treatment Related Adverse Events as Assessed by CTCAE 5. [ Time Frame: 6 Months ]
    National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  2. The proportion of patients requiring secondary immune suppression-Infliximab [ Time Frame: 7 Weeks ]
    patients randomly assigned to infliximab, secondary immune support will be defined as requiring subsequent treatment with steroids. The proportions of patients in each treatment arm requiring secondary immune suppression will be summarized and presented with 90% exact binomial confidence intervals

  3. The proportion of patients requiring secondary immune suppression-Steroids [ Time Frame: 7 Weeks ]
    patients randomly assigned to steroids, secondary immune support will be defined as requiring subsequent treatment with steroids. The proportions of patients in each treatment arm requiring secondary immune suppression will be summarized and presented with 90% exact binomial confidence intervals

  4. Time to steroid-free remission [ Time Frame: randomization to grade-1 or lower symptoms of colitis and less than 7.5 mg a day of prednisone or equivalent or up to 6 months ]
    The initial analysis of steroid-free remission will be based on cumulative incidence (1-Kaplan-Meier estimates).

  5. Rate of Symptom Remission at 72 hours [ Time Frame: 72 hours ]
    The proportion of patients in each treatment arm who have colitis symptom reduction to grade-1 or less within 72 hours of starting randomized treatment will be summarized and presented with 90% exact binomial confidence intervals. The treatment arms will be compared using Fisher's exact tests.

  6. Rate of Symptom Remission at 4 Weeks [ Time Frame: 4 weeks ]
    The proportion of patients in each treatment arm who have colitis symptom reduction to grade-1 or less within 72 hours of starting randomized treatment will be summarized and presented with 90% exact binomial confidence intervals. The treatment arms will be compared using Fisher's exact tests.

  7. Proportion of patients with colectomy or colitis-specific mortality [ Time Frame: 7 weeks ]
    The proportions of patients with colectomy or colitis-specific mortality (investigator assessed) will be presented by treatment arm with 90% exact binomial confidence intervals

  8. Cumulative steroid exposure [ Time Frame: 7 weeks ]

    Cumulative steroid exposure over time for each patient will be calculated by adding the number of doses multiplied by strength of dose over the total follow-up time. Steroid exposure will be summarized descriptively for each treatment arm, and compared using a Wilcoxon rank-sum test.

    With 20 patients per treatment arm, a Wilcoxon rank-sum test will have 80% power to detect a 41difference in cumulative steroid exposure that is 0.85 times the common standard deviation, assuming a one-sided, type-I error of 10


  9. Progression Free Survival [ Time Frame: duration of time from start of randomization to time of progression or death, whichever occurs first or up to 24 months. ]
    summarized using the method of Kaplan-Meier and compared using stratified log-rank tests

  10. Overall Survival [ Time Frame: the duration of time from start of randomization to time of death or up to 24 months ]
    summarized using the method of Kaplan-Meier and compared using stratified log-rank tests

  11. Overall Response Rate [ Time Frame: proportion of evaluable patients who achieve either a (complete response) CR or (partial response) PR or up to 24 Months ]
    Response rates will be summarized by treatment arm and presented with 90% exact binomial confidence intervals. The comparison of response rates between treatment arms will use Fisher's exact test



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18
  • Stage III/IV melanoma
  • Treatment with ipilimumab or ipilimumab in combination with PD-1or PD-L1 blockade within the past 8 weeks; investigational combinations will be permitted provided that they include ipilimumab and a drug targeting PD-1 and/or PD-L1
  • Meets eligibility requires for treatment with ipilimumab
  • Patients with brain metastases and who have received radiation are eligible
  • Prior treatment with targeted or alternative immunotherapy is allowed, provided that these medications were discontinued prior to initiation of the current ipilimumab containing treatment regimen
  • Grade 2-4 diarrhea by Common Terminology Criteria for Adverse Events (CTCAE) onset after treatment
  • Prior to randomization, endoscopically determined colitis, according to Mayo Scoring system, score of 1-3
  • Patients will be permitted to have received up to 3 doses of systemic corticosteroids within 72 hours (up to a maximum dose of 2 mg/kg) prior to endoscopy and randomization
  • Hepatitis B surface antigen, surface antibody, and core antibody must be sent but will not need to be resulted prior to enrollment

Exclusion Criteria:

  • Prior history of inflammatory colitis related to immune checkpoint inhibitors requiring treatment with > 10 mg/day of prednisone or equivalent, or any other immunosuppressive medication
  • Concurrent immune-related Adverse Event (irAE) requiring treatment with systemic corticosteroids (dose equivalent of prednisone 10 mg/day or higher) or another systemic immune suppressing medication within the past 10 days
  • Current use of any immune suppressing biologic medication, or use within the last 4 weeks; immune stimulating medications such as checkpoint blockade are explicitly permitted
  • Current use of combination treatment with an investigation immunotherapy targeting a pathway other than PD-1 or PD-L1, concurrent chemotherapy, or targeted therapy
  • Previous adverse reaction to infliximab or corticosteroids
  • Colonic perforation or abscess
  • History of Hepatitis B or C with a positive viral load, untreated mycobacterium tuberculosis, or active herpes zoster infection; current negative testing results will not be required to be sent prior to study enrollment
  • Positive testing for C Difficile or another colonic infection
  • Current bacterial infection requiring antibiotic treatment, or systemic fungal infection
  • Prior history of inflammatory bowel disease, microscopic colitis or segmental colitis associated with diverticulosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04305145


Contacts
Layout table for location contacts
Contact: Michael Dougan, MD, PHD 617-726-3527 Michael_Dougan@DFCI.HARVARD.EDU

Locations
Layout table for location information
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Contact: Michael Dougan, MD, PhD    617-726-3527    Michael_Dougan@DFCI.HARVARD.EDU   
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Contact: Elizabeth Buchbinder, MD    617-632-5055    Elizabeth_buchbinder@dfci.harvard.edu   
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Layout table for investigator information
Principal Investigator: Michael Dougan, MD, PHD Massachusetts General Hospital
Layout table for additonal information
Responsible Party: Michael Dougan, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04305145    
Other Study ID Numbers: 19-763
First Posted: March 12, 2020    Key Record Dates
Last Update Posted: March 12, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: Massachusetts General Hospital (MGH) - Contact the Partners Innovations team at http://www.partners.org/innovation

Layout table for additional information
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.: No
Keywords provided by Michael Dougan, Massachusetts General Hospital:
Melanoma Stage III
Melanoma Stage IV
Side Effect of Drug
Colitis
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Colitis
Drug-Related Side Effects and Adverse Reactions
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Chemically-Induced Disorders
Prednisone
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Infliximab
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs