The iCaD Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

22 Aug 2023 → ongoing

Decision date (initial)

2023-05-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The objectives of the study are to compare the efficacy and safety of an anti-inflammatory regimen consisting of initial infliximab concomitant to corticosteroid to corticosteroid alone for the treatment of severe ICI induced colitis/diarrhoea.

Conditions and MedDRA coding

Immune checkpoint inhibitor related colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Untreated mCTCAE grade 2-4 diarrhoea or colitis, or persistent mCTCAE grade 2 diarrhoea after administration of loperamide or equivalent for mCTCAE grade ≤ 2 diarrhoea
2. No signs of colonic perforation or infection
3. Age ≥ 18
4. Understands the nature and purpose of the study and the study procedures and has signed informed consent
5. Is able to read, understand, and complete questionnaires and daily components of the Patient Diary for the study period
6. Histologically confirmed malignant solid tumours
7. Treatment with immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1 or anti-PD-L1) within the past 12 weeks. Immune checkpoint inhibitors can be administered as single agents or as combination therapy with anti-CTLA-4 and anti-PD-1
8. No probability of a concomitant treatment (e.g. laxatives) other than the immune checkpoint inhibitor being the causal drug for the colitis or diarrhoea
9. Prior treatment with immune checkpoint inhibitors is allowed
10. Usage of prednisolone ≤ 10 mg daily for non irAE is allowed
11. Diagnostic work up including screening for viral hepatic infection and QuantiFERON-TB for mycobacterium tuberculosis must be requisitioned but will not need to be reported prior to study enrolment
12. Women of child bearing potential must have a negative serum (preferred) or urine pregnancy test within 72 hours prior to registration. Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e. females who have had evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
13. Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and after the study treatment: for at least 6 months after the last study treatment, or depending on the duration antineoplastic treatment Note: A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), Intrauterine device (IUD), Intrauterine hormone-releasing system (IUS), Bilateral tubal occlusion, Vasectomized partner, Sexual abstinence

Exclusion criteria 9

1. Prior history of inflammatory bowel disease, colitis, or diarrhoea requiring treatment with any corticosteroid, or any other immunosuppressant medication
2. Prior history of recurrent bowel disease including symptomatic diverticulosis
3. Current positive testing for Clostridium difficile or other colonic infection
4. Current bacterial infection requiring antibiotic treatment, or systemic fungal infection
5. Ongoing antibiotic treatment for any reason
6. Treatment with systemic corticosteroids within the last four weeks prior to study enrolment (daily usage of prednisolone ≤ 10 mg for non irAE conditions is accepted)
7. Concurrent immune-related adverse events requiring immunosuppressant medication of any kind
8. Known hypersensitivity or contraindications to systemic corticosteroids or infliximab
9. Prior history of viral hepatitis with a positive viral load, known untreated mycobacterium tuberculosis, or known active herpes zoster infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time (days) to persistent modified CTCAE (mCTCAE; definition according to Table 3) grade ≤ 1 ir-colitis/diarrhoea. Persistent is defined as grade ≤ 1 ir-colitis/diarrhoea for five consecutive days or more with no increase in corticosteroid intake, and the event will be calculated from the first day of grade ≤ 1 ir-colitis/diarrhoea of that period (time frame: seven weeks)

Secondary endpoints 13

1. Proportion of study subjects with grade ≤ 1 ir-colitis/diarrhoea at 72 hours (time frame: 72 hours)
2. Proportion of study subjects with persistent grade ≤ 1 ir-colitis/diarrhoea at three weeks. Persistent is defined as grade ≤ 1 ir-colitis/diarrhoea for five consecutive days or more, and the event will be calculated from the first day of grade ≤ 1 ir-colitis/diarrhoea of that period (time frame: three weeks)
3. Proportion of study subjects with a corticosteroid-free clinical remission (grade ≤ 1 ir-colitis/diarrhoea) after seven weeks (time frame: seven weeks)
4. Proportion of study subjects requiring rescue immunosuppressive medication; Arm A (initial corticosteroid only): infliximab if no improvement to grade ≤ 2 ir-colitis/diarrhoea after 3 days (time frame: seven weeks); Arm B (initial infliximab): second dose infliximab according to physicians decision if no improvement to grade ≤ 2 ir-colitis/diarrhoea after seven days
5. Cumulative corticosteroid exposure (time frame: seven weeks)
6. QoL by means of EORTC-QLQ-C30 questionnaire and selected PRO-CTCAE items at baseline, 3, 12, 24, and 52 weeks after randomisation (time frame: 52 weeks)
7. Proportion of study subjects with treatment related adverse events as assessed by CTCAE v5.0 (time frame: 12 weeks)
8. Proportion of study subjects with colectomy or colitis-specific mortality (time frame: seven weeks)
9. Proportion of study subjects with recurrence of ir-colitis/diarrhoea on subsequent reintroduction of ICI
10. Subgroup analyses stratified for ipilimumab containing ICI for time (days) to persistent grade ≤ 1 ir-colitis/diarrhoea. Persistent is defined as grade ≤ 1 ir-colitis/diarrhoea for five consecutive days or more, and the event will be calculated from the first day of grade ≤ 1 ir-colitis/diarrhoea of that period (time frame: seven weeks)
11. Progression Free Survival stratified by cancer type (time frame: duration of time from start of randomisation to time of progression or death, whichever occurs first or up to 24 months)
12. Overall Survival stratified by cancer type (time frame: the duration of time from start of randomisation to time of death or up to 24 months)
13. Translational research projects to explore the diversity and evolution of the immunologic cells and faecal microbiome from initiation of immune checkpoint inhibition, to the event of ir-colitis/diarrhoea, and to resolution after immunosuppressive therapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J B Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Christina H Ruhlmann

Public contact point

Organisation

Odense University Hospital

Contact name

Christina H Ruhlmann

Third parties 1

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications