Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR ) Combined With Anti-PD1，Chemotherapy and Target Therapy 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)
Fudan University
116 participants
Mar 1, 2024
INTERVENTIONAL
Conditions
Summary
To improve the survival in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC) by loco-regional therapy with personalized ultra-fractionated radiation plus immunotherpy.
Eligibility
Inclusion Criteria11
- 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 Criteria18
- 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.
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Interventions
Radiation therapy will be delivered every 3 weeks on the PULSAR schedule to achieve optimal local control of metastatic cancer and augment the effects of sintilimab.
Sintilimab will be given at 200 mg q3w every 3 weeks and schedule to the next day of every pulses of radiation.
First-line standard systemic therapies in cohort A include: FOLFOX/FOLIRI/XELOX+ bevacizumab, FOLFOX/FOLIRI/XELOX+cetuximab (KRAS/NRAS/BRAF WT and left-sided tumors only). Second-line standard systemic therapies in cohort B include: FOLFOX/XELOX+ bevacizumab, FOLFOX/XELOX+cetuximab (KRAS/NRAS/BRAF WT), FOLFIRI/irinotecan+raltitrexed/irinotecan/+bevacizumab, FOLFIRI/irinotecan+raltitrexed/irinotecan/+cetuximab (KRAS/NRAS/BRAF WT), based on the previous first-line chemotherapy and adverse events.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06841159