Melanoma Stage IIIPhase 2NCT04305145
Infliximab for Treatment of Immune Checkpoint Inhibitor Colitis
A Phase 2 study testing Infliximab, Methylprednisolone and Prednisone in people with Melanoma Stage III and Melanoma Stage IV, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
The goal of this clinical trial is to compare the safety and effectiveness of infliximab compared to steroids for the treatment of immune checkpoint inhibitor-induced colitis (ICI colitis) in patients with stage III/IV skin cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage III, Melanoma Stage IV, Skin Cancer Stage III
- What is being tested?
- Infliximab, Methylprednisolone and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 2 sitesUnited States
- Study dates
- 31 Aug 2020to 30 Jun 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18
- Stage III/IV skin cancer
- Treatment with CTLA-4 inhibitor alone or in combination with PD-1or PD-L1 blockade within the past 8 weeks
- Clinically significant diarrhea resulting in the decision to pause immunotherapy treatment
- Endoscopically visible colitis (Mayo 1-3) at the time of screening
Who cannot join
- 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 present at the time of screening
Show all 10Show fewer
- History of Hepatitis B or C with a positive viral load, untreated mycobacterium tuberculosis, or active herpes zoster 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
- Received more than 3 doses of systemic corticosteroids, or receive dsystemic corticosteroids at a dose exceeding 2mg/kg methylprednisolone or equivalent, within 72 hours prior to endoscopy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Phase II Study of Infliximab for the Treatment of Immune Checkpoint Inhibitor Colitis
The goal of this clinical trial is to compare the safety and effectiveness of infliximab compared to steroids for the treatment of immune checkpoint inhibitor-induced colitis (ICI colitis) in patients with stage III/IV skin cancer.
The main questions this study aims to answer are:
- How many patients treated with infliximab experience steroid-free disease resolution after 7 weeks?
- How many patients treated with steroids experience steroid-free disease resolution after 7 weeks?
Read the 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 caused by immune checkpoint inhibitors (ICIs) that target a protein called CTLA-4. An example of one of these ICIs is ipilimumab, which has been approved by the FDA to treat metastatic melanoma.
The names of the treatments involved in this study are:
- Infliximab
- Methylprednisolone
- Prednisone
The FDA has approved infliximab, methylprednisolone, and prednisone to treat many conditions affecting the immune system, including colitis.
Participants will receive a CTLA-4 inhibitor, like ipilimumab, and any other cancer treatments as part of their regular care for stage III/IV skin cancer at the discretion of treating oncologist.
Participants who enroll in this study will undergo one or more flexible sigmoidoscopies or colonoscopies as part of their clinical care. The first of these procedures would occur at the time of study enrollment, and the second may occur after several weeks of treatment at the discretion of the study doctor. During these procedures, biopsies will be collected for clinical purposes as well as for research purposes. Blood will also be collected for research at the time of enrollment and at the time of study completion. Any extra samples for research would only be collected if it is safe for the participant.
Participants will also complete weekly follow-ups either over the phone or in-person that may last about 10 minutes. During these visits, participants will be asked about any new symptoms or changes in their health, their medications, and their GI symptoms. Blood for research may be collected at one or more of these visits if it coincides with a scheduled clinical blood draw.
Participants are expected to be on study treatment for approximately 7 weeks. Once participants complete the study treatment, the study team will review their medical records every 6 months for any changes in their health.
It is expected that about 42 people will take part in this research study.
- Conditions
- Melanoma Stage III, Melanoma Stage IV, Skin Cancer Stage III, Skin Cancer Stage IV, Drug-Induced Colitis, Drug Toxicity
- Being tested
- Infliximab, Methylprednisolone, Prednisone
- Keywords
- Melanoma, Skin cancer, Drug toxicity, Colitis, Immune checkpoint inhibitor, Immunotherapy toxicity, Immune-related adverse event
- Medical subject headings
- Melanoma, Skin Neoplasms, Drug-Related Side Effects and Adverse Reactions, Colitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called AVSOLA, Ixifi, Remicade, Renflexis
Infusion
Also called Solu-Medrol, Duralone, Medralone, Medrol
Infusion
PrednisoneDrug
Also called Deltasone, Prednicot, predniSONE Intensol, Rayos
Orally
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Experimental | Patients randomized to this arm will receive IV infliximab regardless of whether they are hospitalized due to their colitis.
* Infliximab: Predetermined dose of intravenous infliximab, up to 3 times over 7 weeks
* Crossover 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 (corticosteroids) at full initial dosing. Receives: Drug: Infliximab |
| Corticosteroids | Experimental | Patients randomized to this arm will receive IV steroids or oral steroids depending on whether the severity of their colitis requires hospitalization ("inpatient").
* Inpatient: Predetermined intravenous dose of methylprednisolone, 2x daily up until patients can safely be transitioned to an oral prednisone taper
* Outpatient: Predetermined oral dose of predisone, daily over 7 weeks
Crossover 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 (infliximab) at full initial dosing. Receives: Drug: Methylprednisolone; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with Steroid-Free Colitis
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.
Measured: 7 weeks
Secondary outcomes (11)
Proportion of Participants with Treatment Related Adverse Events as Assessed by CTCAE 5.
National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: 6 Months
The proportion of patients requiring secondary immune suppression-Infliximab
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
Measured: 7 Weeks
The proportion of patients requiring secondary immune suppression-Steroids
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
Measured: 7 Weeks
Time to steroid-free remission
The initial analysis of steroid-free remission will be based on cumulative incidence (1-Kaplan-Meier estimates).
Measured: 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
Rate of Symptom Remission at 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.
Measured: 72 hours
Rate of Symptom Remission at 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.
Measured: 4 weeks
Proportion of patients with colectomy or colitis-specific mortality
The proportions of patients with colectomy or colitis-specific mortality (investigator assessed) will be presented by treatment arm with 90% exact binomial confidence intervals
Measured: 7 weeks
Cumulative steroid exposure
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
Measured: 7 weeks
Progression Free Survival
summarized using the method of Kaplan-Meier and compared using stratified log-rank tests
Measured: duration of time from start of randomization to time of progression or death, whichever occurs first or up to 24 months.
Overall Survival
summarized using the method of Kaplan-Meier and compared using stratified log-rank tests
Measured: the duration of time from start of randomization to time of death or up to 24 months
Overall Response Rate
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
Measured: proportion of evaluable patients who achieve either a (complete response) CR or (partial response) PR or up to 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2020
- Study start31 Aug 2020
- Primary completion30 Jun 2030 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage IIIStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Responsible party
- Principal investigator, Long Nguyen, Massachusetts General Hospital
- Investigators
- Long Nguyen, MD, MS, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04305145
- Sponsor's protocol ID
- 19-763
- Status last verified
- Oct 2026
- First submitted
- 9 Mar 2020
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Infliximab for the Treatment of Immune Checkpoint Inhibitor Colitis
- ClinicalTrials.gov ID
- NCT04305145
- Acronym / sponsor ID
- 19-763
- Conditions
- Melanoma Stage III, Melanoma Stage IV, Skin Cancer Stage III, Skin Cancer Stage IV, Drug-Induced Colitis, Drug Toxicity
- Keywords
- Melanoma, Skin cancer, Drug toxicity, Colitis, Immune checkpoint inhibitor, Immunotherapy toxicity, Immune-related adverse event
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Study start
- 31 Aug 2020 (actual)
- Primary completion
- 30 Jun 2030 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 12 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to compare the safety and effectiveness of infliximab compared to steroids for the treatment of immune checkpoint inhibitor-induced colitis (ICI colitis) in patients with stage III/IV skin cancer.
The main questions this study aims to answer are:
- How many patients treated with infliximab experience steroid-free disease resolution after 7 weeks?
- How many patients treated with steroids experience steroid-free disease resolution after 7 weeks?
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 caused by immune checkpoint inhibitors (ICIs) that target a protein called CTLA-4. An example of one of these ICIs is ipilimumab, which has been approved by the FDA to treat metastatic melanoma.
The names of the treatments involved in this study are:
- Infliximab
- Methylprednisolone
- Prednisone
The FDA has approved infliximab, methylprednisolone, and prednisone to treat many conditions affecting the immune system, including colitis.
Participants will receive a CTLA-4 inhibitor, like ipilimumab, and any other cancer treatments as part of their regular care for stage III/IV skin cancer at the discretion of treating oncologist.
Participants who enroll in this study will undergo one or more flexible sigmoidoscopies or colonoscopies as part of their clinical care. The first of these procedures would occur at the time of study enrollment, and the second may occur after several weeks of treatment at the discretion of the study doctor. During these procedures, biopsies will be collected for clinical purposes as well as for research purposes. Blood will also be collected for research at the time of enrollment and at the time of study completion. Any extra samples for research would only be collected if it is safe for the participant.
Participants will also complete weekly follow-ups either over the phone or in-person that may last about 10 minutes. During these visits, participants will be asked about any new symptoms or changes in their health, their medications, and their GI symptoms. Blood for research may be collected at one or more of these visits if it coincides with a scheduled clinical blood draw.
Participants are expected to be on study treatment for approximately 7 weeks. Once participants complete the study treatment, the study team will review their medical records every 6 months for any changes in their health.
It is expected that about 42 people will take part in this research study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Experimental | Drug: InfliximabPatients randomized to this arm will receive IV infliximab regardless of whether they are hospitalized due to their colitis. * Infliximab: Predetermined dose of intravenous infliximab, up to 3 times over 7 weeks * Crossover 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 (corticosteroids) at full initial dosing. |
| Corticosteroids | Experimental | Drug: Methylprednisolone, Drug: PrednisonePatients randomized to this arm will receive IV steroids or oral steroids depending on whether the severity of their colitis requires hospitalization ("inpatient"). * Inpatient: Predetermined intravenous dose of methylprednisolone, 2x daily up until patients can safely be transitioned to an oral prednisone taper * Outpatient: Predetermined oral dose of predisone, daily over 7 weeks Crossover 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 (infliximab) at full initial dosing. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18
- Stage III/IV skin cancer
- Treatment with CTLA-4 inhibitor alone or in combination with PD-1or PD-L1 blockade within the past 8 weeks
- Clinically significant diarrhea resulting in the decision to pause immunotherapy treatment
- Endoscopically visible colitis (Mayo 1-3) at the time of screening
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabAlso: AVSOLA, Ixifi, Remicade, RenflexisInfusion | Drug | Infliximab |
| MethylprednisoloneAlso: Solu-Medrol, Duralone, Medralone, MedrolInfusion | Drug | Corticosteroids |
| PrednisoneAlso: Deltasone, Prednicot, predniSONE Intensol, RayosOrally | Drug | Corticosteroids |
Primary outcome
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.
11 secondary outcomes
Proportion of Participants with Treatment Related Adverse Events as Assessed by CTCAE 5.
Time frame: 6 Months
The proportion of patients requiring secondary immune suppression-Infliximab
Time frame: 7 Weeks
The proportion of patients requiring secondary immune suppression-Steroids
Time frame: 7 Weeks
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
Rate of Symptom Remission at 72 hours
Time frame: 72 hours
Rate of Symptom Remission at 4 Weeks
Time frame: 4 weeks
Proportion of patients with colectomy or colitis-specific mortality
Time frame: 7 weeks
Cumulative steroid exposure
Time frame: 7 weeks
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.
Overall Survival
Time frame: the duration of time from start of randomization to time of death or up to 24 months
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Long Nguyen, MD, MS principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Infliximab, Methylprednisolone and Prednisone in people with Melanoma Stage III and Melanoma Stage IV, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with Steroid-Free Colitis (time frame: 7 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.