Immunotherapy in Patients With Early dMMR Rectal Cancer

Last updated: April 2, 2024
Sponsor: Odense University Hospital
Overall Status: Active - Recruiting

Phase

2

Condition

Colorectal Cancer

Colon Cancer

Digestive System Neoplasms

Treatment

Ipilimumab

Nivolumab

Clinical Study ID

NCT05732389
KFE nr. 22.20
  • Ages > 18
  • All Genders

Study Summary

Colorectal cancer (CRC) is the third most common cancer (1.8 million cases) and the third most common cause of cancer-related death (0.8 million deaths) worldwide in 2018, and rectal cancer accounts for roughly one-third of CRC.

The main curative treatment modality for patients with rectal cancer is surgery, often combined with chemotherapy and/or radiotherapy (RT). The global recognition of total mesorectal excision (TME), that decreased locoregional recurrence (LRR) by itself, questioned the need for radiotherapy (RT) before or after surgery. Several randomized trials have demonstrated the importance of preoperative RT (short course RT or long course chemo-radiotherapy (CRT)) in reducing LRR, in patients with high-risk rectal cancer. However, RT or CRT does not improve overall survival, and in addition neoadjuvant RT/CRT followed by TME is associated with perioperative morbidity and the risk is increasing with age. Therefore, ongoing trials are testing other strategies, such as the omission of (C)RT or even avoidance of surgery.

In May 2022, a presentation with simultaneous NEJM publication showed that 14/14 patients with dMMR rectal cancer obtained complete response after six months (9 cycles every 3 weeks) of immunotherapy (dostarlimab). Thus, the investigators have now become confident that immunotherapy without surgery will be the "new standard", and the investigators will recommend a W&W strategy in patients with rectal cancer obtaining major tumor shrinkage and these patients will be followed carefully with clinical and molecular evaluation (which was not part of the NEJM paper). No patient in the NEJM paper had progressive disease and therefore the investigators recommend a second cycle of immunotherapy (instead of resection in unclear cases) and re-evaluation. The investigators are confident that 1 or 2 cycles of immunotherapy will result in complete radiological, pathological, and molecular response in a substantial number of patients and this short duration of therapy will reduce toxicity and especially drug costs.

In conclusion, immunotherapy in patients with dMMR CRC tumors may completely eradicate the primary cancer and regional lymph nodes leading to a possibility for organ-sparing medical treatments, and the investigators are confident that this new strategy of 1 or 2 cycles of immunotherapy will be the future standard of care, and in Denmark the investigators have the chance to monitor these patients closely with clinical and high-level molecular follow-up.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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

Exclusion

Exclusion Criteria:

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

Study Design

Total Participants: 39
Treatment Group(s): 2
Primary Treatment: Ipilimumab
Phase: 2
Study Start date:
February 01, 2023
Estimated Completion Date:
February 28, 2027

Connect with a study center

  • Department of Oncology, Odense University Hospital

    Odense, 5000
    Denmark

    Active - Recruiting

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