POLARIS — Ablative radiotherapy with immunotherapy for people with multiple metastatic lesions
STM-06: POLARIS-POlymetastic Lesion Ablative Radiotherapy With Immunotherapy Study
This pilot tests whether giving focused high-dose radiation to up to 10 metastatic tumors while patients are on immunotherapy helps people with advanced solid tumors who have 3–10 metastases.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 28 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Illinois at Chicago Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, radiation, prednisone |
| Locations | 1 site (Chicago, Illinois) |
| Trial ID | NCT07269080 on ClinicalTrials.gov |
What this trial studies
This is a non-randomized, two-arm Phase 1 pilot in which about 28 participants (approximately 14 per cohort) with advanced solid tumors and 3–10 metastatic lesions will receive ablative radiotherapy to up to 10 lesions while on immunotherapy. Blood will be collected for circulating tumor DNA (ctDNA) about 8 weeks after completing radiation, and participants will undergo imaging and serial ctDNA monitoring afterward. Additional treatments and ongoing disease assessments are managed by the treating oncologist. If a participant does not complete the planned radiation course, a final study visit is scheduled about 30 days after their last radiation fraction.
Who should consider this trial
Good fit: Adults (≥18 years) with advanced solid tumors on immunotherapy who have 3–10 metastatic sites (excluding primary tumor) located outside the GI tract, brainstem, and skin, with ECOG 0–2 and adequate organ function are the ideal candidates.
Not a fit: Patients with metastases in the GI tract, brainstem, or skin, more than 10 metastatic lesions, poor organ function, pregnancy, or inability to receive or complete ablative radiation are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, combining ablative radiotherapy with immunotherapy could improve systemic tumor control and delay disease progression for patients with limited metastatic burden.
How similar studies have performed: Previous trials combining stereotactic ablative radiotherapy with systemic therapy (including immunotherapy) have shown promising signals in oligometastatic disease, but applying ablative RT to as many as 10 lesions is less well studied and remains exploratory.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥ 18 years of age at the time of consent * ECOG (0, 1, or 2) within 30 days prior to registration. * Subjects with advanced solid tumors with at least 3 but no more than 10 sites of metastatic disease, excluding the primary tumor. * Disease site must be outside of the GI tract (including esophagus, stomach, small or large bowel, and mesenteric lymph nodes), brainstem, and skin. * Demonstrates adequate organ function. All screening labs are to be obtained within 30 days prior to registration. * Able to provide written informed consent and HIPAA authorization for release of personal health information via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization. If a subject is unable to consent, a Legally Authorized Representative (LAR) may provide consent on their behalf. * Women of childbearing potential must not be pregnant or breastfeeding. A negative serum or urine pregnancy test is required per institutional practice guidelines. * As determined at the discretion of the enrolling physician or protocol designee, the ability of the subject to understand and comply with study procedures for the entire length of the study. * Have a life expectancy of at least 3 months. * Subjects receiving treatment for \>3 months with an FDA-approved immunotherapy agent such as a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, or an LAG-3 inhibitor; either as monotherapy or in combination with another FDA-approved immunotherapy agent. Subjects may have received prior combination cytotoxic chemotherapy and immunotherapy, but must be receiving only immunotherapy for at least 30 days prior to registration. * Cohort A: Subjects with investigator-assessed stable disease or partial response after \> 3 months of immunotherapy treatment prior to registration * Cohort B: Subjects with oligo-progression defined as having at least 3 sites of disease during their disease course, with at least 1 but up to 5 sites of progressive disease within 3 months of registration. Subjects must have investigator-assessed stable disease, partial response, or complete response as prior best response to immunotherapy and have been on immunotherapy for at least 3 months prior to registration. Exclusion Criteria: * Inability to treat all sites of disease * \>10 metastatic lesions at any point in the disease course * History of interstitial lung disease or G3 or worse pneumonitis * Malignant pleural effusion * Active infection requiring IV antibiotics * Active autoimmune disease requiring immunosuppression in the last two years from enrollment. * Significant medical comorbidities precluding radiotherapy as determined by the treating physician. * Use of systemic corticosteroids equivalent to prednisone ≥10 mg daily within 14 days prior to registration, or requirement for systemic corticosteroids at screening for disease control, unless used as physiologic replacement (e.g., adrenal insufficiency). Subjects who require systemic steroids ≥10 mg/day for clinical management will be ineligible. * Substantial overlap with a previously treated radiation volume. * For patients with liver metastases, moderate/severe liver dysfunction (Child-Pugh B or C) * Patients with symptomatic brain metastases, a single metastasis greater than 5 cm in size, or any brain metastasis greater than 3 cm in size. Patients with total brain metastases volume exceeding 30 cc. * Clinical or radiologic evidence of spinal cord compression. * Metastatic disease involving the GI tract (esophagus, stomach, small or large bowel, mesenteric lymph nodes), disease in the brainstem, or skin * Pregnant or nursing * Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen, as determined by the treating medical oncologist. * Other major comorbidity, as determined by the study PI
Where this trial is running
Chicago, Illinois
- University of Illinois at Chicago — Chicago, Illinois, United States (Recruiting)
Study contacts
- Principal investigator: Ryan Nguyen, DO — University of Illinois at Chicago
- Study coordinator: Ryan Nguyen, DO
- Email: rnguye8@uic.edu
- Phone: (312) 996-9424
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.