125I Seed Implantation Plus Systemic Therapy for Oligoprogressive NSCLC or Colorectal Cancer

Phase 2Not Yet RecruitingNCT07333651

Li Min90 enrolled

Overview

Most patients with metastatic cancer eventually develop resistance to systemic therapy. A subset of patients experience oligoprogression, characterized by progression at a limited number of lesions while other disease sites remain controlled by ongoing systemic therapy. This randomized phase 2 trial evaluates whether image-guided 125I seed implantation targeting all oligoprogressive extracranial lesions, combined with standard-of-care systemic therapy, improves progression-free survival compared with standard-of-care systemic therapy alone in patients with metastatic NSCLC or CRC.

This is a prospective, open-label, randomized phase 2 controlled trial enrolling adults with histologically confirmed metastatic NSCLC or colorectal cancer who developed extracranial oligoprogression (≤5 progressive lesions) on PET/CT or CT while receiving at least first-line systemic therapy (including maintenance). Eligible patients will be randomized 1:1 to (1) standard-of-care systemic therapy per treating physician discretion, or (2) image-guided 125I seed implantation to all oligoprogressive lesions plus standard-of-care systemic therapy. Oligoprogression will be determined by predefined imaging response criteria (RECIST and/or PERCIST, depending on baseline imaging modality), with confirmation by designated study radiologists. Follow-up imaging will be performed at 8 weeks (±2 weeks) after randomization and every 12 weeks (±2 weeks) thereafter to assess disease status. The primary endpoint is progression-free survival measured up to 12 months. Secondary endpoints include overall survival, time to initiation of a new systemic therapy, local control of implanted lesions, safety, and quality of life. Optional exploratory objectives may include circulating tumor DNA dynamics and metabolic PET parameters.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

Standard-of-Care Systemic TherapyOTHER

Standard systemic anticancer therapy administered according to current clinical guidelines and treating physician discretion, which may include chemotherapy, immunotherapy, targeted therapy, and/or maintenance therapy.

125I Seed ImplantationPROCEDURE

Image-guided implantation of iodine-125 (125I) radioactive seeds to all extracranial oligoprogressive lesions for local tumor control, performed under CT or PET/CT guidance according to institutional standards.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years. * Histologically or cytologically confirmed metastatic non-small cell lung cancer (NSCLC) or colorectal cancer (CRC). * Presence of metastatic disease with extracranial oligoprogression, defined as progression in up to five (≤5) individual lesions on CT or PET/CT imaging, while other known disease sites remain stable or controlled. * Received at least one prior line of standard systemic anticancer therapy, including maintenance therapy, for metastatic disease. * All oligoprogressive lesions are technically feasible and considered safe for image-guided 125I seed implantation, as determined by the treating interventional team. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Adequate organ function to undergo interventional procedures and systemic therapy, per institutional standards. * Ability to understand and willingness to sign written informed consent. Exclusion Criteria: * Pregnancy or breastfeeding. * Leptomeningeal disease or diffuse central nervous system involvement. Uncontrolled infection or serious medical comorbidities that, in the investigator's judgment, would preclude safe participation or interventional procedures. * Prior radiotherapy or brachytherapy requiring re-irradiation to the same tumor location planned for 125I seed implantation. * Known bleeding diathesis or uncorrectable coagulation disorders contraindicating interventional procedures. * Any other condition that, in the investigator's judgment, would make the patient unsuitable for the study.

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

Progression-free survival is defined as the time from randomization to systemic disease progression or death from any cause, whichever occurs first. Disease progression will be assessed using RECIST version 1.1 and/or PERCIST criteria based on the baseline imaging modality.

Time frame: From randomization up to 12 months

Secondary Outcomes

Overall Survival (OS)

Overall survival is defined as the time from randomization to death from any cause.

Time frame: From randomization up to 24 months

Time to Initiation of a New Systemic Therapy (TTNT)

Time to initiation of a new systemic therapy is defined as the time from randomization to the start of a new line or regimen of systemic anticancer therapy due to disease progression or clinical decision.

Time frame: From randomization up to 12 months

Local Control of Treated Lesions

Local control is defined as the absence of in-field progression of oligoprogressive lesions treated with 125I seed implantation, assessed on follow-up imaging.

Time frame: From intervention to 12 months after randomization

Safety and Treatment-Related Adverse Events

Safety is assessed by the incidence and severity of adverse events, including procedure-related toxicities, graded according to the Common Terminology Criteria for Adverse Events (CTCAE).

Time frame: From intervention through 12 months