Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR ) Combined With Anti-PD1，Chemotherapy and Target Therapy for Metastatic Colorectal Cancer

NCT06841159 | Recruiting Phase 2

• 1 other identifier: FDRT-2023-421-3540
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Microsatellite Stable Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  time from the date of start treatment until disease progression or censored at last follow-up or death.

  up to 2 years

Secondary Outcomes (5)

• Overall Survival (OS)

  up to 3 year

• Objective response rate (ORR)

  up to 1 year

• Disease control rate (DCR)

  up to 1 year

• Duration of response (DOR)

  up to 2 years

• Adverse events

  up to 3 years

Study Arms (1)

a first-line cohort A and a second-line cohort B

EXPERIMENTAL

Personalized Ultra-fractionated Stereotactic Radiotherapy (PULSAR) plus sintilimab and standard systemic therapy.

Radiation: Ultra-fractionated radiation therapy; Drug: Sintilimab; Drug: Standard systemic therapy

Interventions

Ultra-fractionated radiation therapy RADIATION

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.

a first-line cohort A and a second-line cohort B

Sintilimab DRUG

Sintilimab will be given at 200 mg q3w every 3 weeks and schedule to the next day of every pulses of radiation.

a first-line cohort A and a second-line cohort B

Standard systemic therapy DRUG

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.

a first-line cohort A and a second-line cohort B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University

Shanghai, China

RECRUITING

MeSH Terms

Interventions

sintilimab

Central Study Contacts

Zhen Zhang, MD,PhD

CONTACT

86-0204256577200; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 29, 2024
• First Posted: February 24, 2025
• Study Start: March 1, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 24, 2025

Record last verified: 2025-02

Locations

CN (1)