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Neoadjuvant Immunotherapy ± Radiotherapy in MSI-H/dMMR Locally Advanced Colorectal Cancer

ConditionColorectal Cancer (MSI-H)
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFudan University

About this trial

This phase II clinical trial evaluates the efficacy and safety of three neoadjuvant regimens in patients with locally advanced microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC): 1) Regimen A: Dual immune checkpoint blockade with nivolumab plus ipilimumab. 2) Regimen B: Nivolumab plus radiotherapy. 3) Regimen C: Nivolumab monotherapy. The primary objectives are to determine whether: 1) Dual immune checkpoint blockade (Regimen A) is superior to nivolumab monotherapy (Regimen C); and 2) Immunotherapy plus radiotherapy (Regimen B) is superior to nivolumab monotherapy (Regimen C). Methods: Participants will be randomized in a 1:1:1 ratio to one of the three arms. For patients with resectable tumors, surgical resection will be performed. In patients with low rectal cancer and poor prospects for sphincter preservation, a watch-and-wait (WW) strategy is an option if a clinical complete response (CR) is achieved following neoadjuvant therapy.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histopathologically confirmed primary colorectal adenocarcinoma.

Radiographic assessment showed a stage II-III based on AJCC Stage 8th ed.

At least 18 years old.

MSI-H or dMMR.

Disqualifiers

Previously received any antitumor therapy for the disease under study, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.

Pregnancy or breastfeeding women.

History of other malignancies within 5 years.

Serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Nivolumab

    Drug

    Nivolumab 240 mg every 2 weeks

  • Ipilimumab (1mg/kg)

    Drug

    Ipilimumab 1 mg/kg every 3 weeks

  • PULSAR

    Radiation

    Irradiation targeted to the primary lesion (5 Gy per fraction, total 4 fractions, delivered every 3 weeks).

  • Radical surgery

    Procedure/Surgery

    Surgical resection will be performed in resectable cases.

  • Watch & wait

    Other intervention

    For patients with low rectal cancer who are unable to preserve the anal sphincter, a watch-and-wait (WW) strategy can be considered if a clinical complete response (CR) is achieved.

Treatment groups

114 Participants
are divided into 3 treatment groups
Group A: anti-PD-1 plus anti-CTLA-4Experimental treatment 4 interventions
Group B: anti-PD-1 plus radiotherapyExperimental treatment 4 interventions
Group C: anti-PD-1 monotherapyActive comparator 3 interventions

Trial outcomes

Primary outcomes

1

Complete regression (CR) rate

Proportion of patients achieving either clinical CR (and undergoing WW) or pathological CR (confirmed by pathology) among all evaluable patients.

Time frame
1 month after surgery or the completion of neoadjuvant therapy

Secondary outcomes

1

R0 resection rate

Proportion of patients who achieve R0 resection.

Time frame
1 month after surgery
2

Objective response rate (ORR)

Proportion of patients with complete response (CR) or partial response (PR) to preoperative multimodal therapy. ORR will be evaluated using RESIST1.1 by CT/MRI of the chest, abdomen, and pelvis.

Time frame
6 months after the enrollment of the last subject
3

Event-free survival (EFS)

The EFS was defined as the time from randomization to the first determination of inoperable disease progression, postoperative local recurrence or distant metastasis, tumor regrowth, or death from any cause, whichever occurs first.

Time frame
36 months after the enrollment of the last subject
4

Overall survival (OS)

OS is defined as the time interval from enrollment to death of any reason or censoring.

Time frame
36 months after the enrollment of the last subject

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fudan University

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: