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.
IPULSAR-CRC is a prospective, single-arm, two-cohort, investigator-initiated phase II trial to investigate the efficacy and safety of Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR ) plus sintilimab in combination with standard systemic therapy in paitents with microsatellite stable metastatic colorectal cancer (MSS mCRC). Eligible patients will be assigned to two cohorts according to previous treatment: a first-line cohort A and a second-line cohort B. Patients in both arms will receive PULSAR, administered in 5 fractions of 6-10 Gy each (30-100 Gy total) at 3 week intervals. Sintilimab will be administered 200mg every 3 weeks and schedule to the next day of every pulses of radiation. Standard systemic therapy will be administered based on previous chemotherapy and adverse reactions to chemotherapy agents and at the discretion of the oncologist.The survival benefits, response rates, and adverse effects will be analyzed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
116
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.
Fudan University
Shanghai, China
RECRUITINGProgression-Free Survival (PFS)
time from the date of start treatment until disease progression or censored at last follow-up or death.
Time frame: up to 2 years
Overall Survival (OS)
from the date of start treatment until the date of death from any cause or censored at last follow-up.
Time frame: up to 3 year
Objective response rate (ORR)
the proportion of patients with the best response of confirmed complete or partial response according to iRECIST in all metastatic lesions.
Time frame: up to 1 year
Disease control rate (DCR)
the proportion of patients with disease control in all metastatic lesions. Disease control is defined as CR, PR, or stable disease (SD) per iRECIST after treatment.
Time frame: up to 1 year
Duration of response (DOR)
time from the first documented objective response to disease progression in patients with confirmed response.
Time frame: up to 2 years
Adverse events
The percentage of patients with treatment-related acute toxicities as assessed by NCI CTCAE v5.0, from treatment initiation until 90 days upon completion of immunotherapy.
Time frame: up to 3 years
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