Immunotherapy in patients with early dMMR rectal cancer. A Danish DCCG phase II trial

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]

Trial duration

31 Jan 2023 → ongoing

Decision date (initial)

2022-07-04

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The purpose of this study is to evaluate the efficacy and tolerability of immunotherapy with nivolumab and ipilimumab in patients with stage 1-3 MSI/dMMR rectal cancer.

Conditions and MedDRA coding

cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥ 18 years.
2. Histologically verified non-metastatic rectal cancer stage 1-3.
3. No indication for local therapy like TEM.
4. Histologically verified dMMR or MSI.
5. Performance status (WHO) of 0-1.
6. No previous chemotherapy, radiotherapy or immunotherapy for colorectal cancer.
7. Adequate haematological function defined as neutrophils  1.5 x 109/l and platelets ≥ 100 x 109/l.
8. Adequate organ function (bilirubin ≤ 1.5 x UNL (upper normal limit), GFR (may be calculated) > 30 ml/min.
9. Women of childbearing potential must have been tested negative in a serum pregnancy test within five days prior to registration. Fertile patients must agree to use a highly effective method of birth control. (i.e., pregnancy rate of less than 1 % per year) during the study and for six months after the discontinuation of study medication.
10. Has provided written informed consent prior to performance of any study procedure.
11. Written informed consent must be obtained according to the local Ethics Committee requirements.

Exclusion criteria 4

1. Any other condition or therapy, which in the investigator’s opinion may pose a risk to the patient or interfere with the study objectives.
2. Concomitant use of systemic glucocorticoids more than the equivalent dose to tablet prednisolone 10 mg/day. Treatment with systemic glucocorticoids must end no later than two weeks before inclusion.
3. Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
4. Known allergy or intolerance to any of the drugs used (nivolumab and ipilimumab).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of patients with clinical complete response evaluated day 93 (+/- 7 days) after one or two cycles of immunotherapy. Complete clinical response will be defined as no visible or palpable tumor examined by rectal exploration (if low tumors), endoscopy and MR-scan. Patients with definite but less than complete regression BUT with a representative biopsy without viable tumor cells will also be classified as cCR in this trial.

Secondary endpoints 6

1. Number of patients with complete biological response after 1 or 2 cycles of immunotherapy.
2. Number of patients without any sign of recurrence after 12 months.
3. Response rate according to mrTRG (24).
4. Adverse events.
5. Correlation between bio-markers (ctDNA and CEA) and outcome.
6. Quality of life (EORCT QLQ-C30 and EORCT QLQ-CR29).

Investigational products

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

Test 2

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

Line Schmidt Tarpgaard

Public contact point

Organisation

Odense University Hospital

Contact name

Line Schmidt Tarpgaard

Third parties 3

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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