Personalized radiation therapy combined with immunotherapy and chemotherapy for metastatic colorectal cancer

Phase 2 Study of Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR ) Combined With Anti-PD1, Chemotherapy and Target Therapy for Metastatic Colorectal Cancer(iPULSAR-CRC)

This study is testing a new combination of personalized radiation therapy, immunotherapy, and chemotherapy to see if it helps people with advanced colorectal cancer live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 116 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, sintilimab
• Locations: 1 site (Shanghai)
• Trial ID: NCT06841159 on ClinicalTrials.gov

What this trial studies

This trial investigates the efficacy and safety of Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) combined with the immunotherapy drug sintilimab and standard systemic therapy in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC). It is a phase II, single-arm trial that assigns patients to two cohorts based on their previous treatment history. Participants will receive PULSAR in five fractions of radiation, along with sintilimab administered every three weeks, and standard systemic therapy tailored to their prior chemotherapy experiences. The study aims to analyze survival benefits, response rates, and adverse effects associated with this treatment approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histopathologically confirmed MSS/pMMR adenocarcinoma of the colon or rectum and specific metastatic conditions.

Not a fit: Patients with extensive metastasis beyond the treatment limits or those who have received prior radiotherapy within the last six months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates for patients with MSS mCRC.

How similar studies have performed: While similar approaches have been explored, this specific combination of therapies in MSS mCRC is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Patient is 18-75 years old at the time of signing the informed consent form.
* ECOG performance status 0-1.
* Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum.
* Distant metastasis lesions are no more than 10 and all sites of disease can be safely treated based on a pre-plan.
* At least one evaluable metastatic lesion for radiotherapy and evaluation according to RECIST 1.1.
* No prior radiotherapy within 6 month.
* Previous system therapy. Patients Group Cohort A: participants who have not previously been treated with first-line chemotherapy. Cohort B: Patients with disease progression after first-line chemotherapy or stopped first-line therapy due to unacceptable toxic effects .
* Has an investigator determined life expectancy of at least 24 weeks.
* Demonstrate adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.
* Non pregnant or lactating patients. Effective contraceptive methods should be used during the study and within 6 months of the last administration.
* Fully informed and willing to provide written informed consent for the trial.

Exclusion Criteria:

* History of checkpoint inhibitor therapy.
* Neutrophil\< 1.5×109/L, PLT\< 100×109/L (PLT\< 80×109/L in patients with liver metastasis), or Hb\< 90 g/L.
* TBIL \> 1.5 ULN, or TBIL \> 2.5 ULN in patients with liver metastasis. AST or ALT \> 2.5 ULN, or ALT and/or AST \> 5 ULN in patients with liver metastasis.
* Cr \> 1.5 ULN, or creatinine clearance\< 50 mL/min (calculated according to Cockcroft Gault formula).
* APTT \> 1.5 ULN, PT \> 1.5 ULN (subject to the normal value of the clinical trial research center).
* Serious electrolyte abnormalities.
* Urinary protein ≥ 2+, or 24-h urine protein ≥1.0 g/24 h.
* Uncontrolled hypertension: SBP \>140 mmHg or DBP \> 90 mmHg.
* A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months.
* A history of heart disease within 6 months.
* Uncontrolled malignant pleural effusion, ascites, or pericardial effusion.
* The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years.
* A history of liver disease including, but not limited to, HBV infection or HBV DNA positive (≥1×104/mL), HCV infection or HCV DNA positive (≥1×103/mL),and liver cirrhosis.
* Pregnant or lactating women or women who may be pregnant have a positive pregnancy test before the first medication, or the female participants themselves and their partners who were unwilling to implement strict contraception during the study period.
* The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.
* Serious mental abnormalities.
* The diameter of brain metastasis is greater than 3 cm or the total volume is greater than 30 cc.
* Clinical or radiological evidence of spinal cord compression, or tumors within 3 mm of the spinal cord on MRI.

Where this trial is running

Shanghai

• Fudan University — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Zhen Zhang, MD,PhD

Conditions Microsatellite Stable Metastatic Colorectal Cancer