Using radiation to delay progression in advanced lung cancer with driver mutations

Radiation Prior to TKI to Delay Progression in Advanced Driver-Mutated Non-small Cell Lung Cancers (RadiaNCe Lung X)

This study is testing if giving radiation therapy to the main lung tumor can help people with advanced lung cancer and specific gene mutations live longer without their cancer getting worse before they start taking a new medication.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medical College of Wisconsin (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Milwaukee, Wisconsin)
• Trial ID: NCT06305715 on ClinicalTrials.gov

What this trial studies

This phase II trial aims to determine if definitive radiation therapy to the primary lung lesion can prolong progression-free survival in treatment-naïve patients with metastatic, driver-mutated non-small cell lung cancer (NSCLC) who will subsequently receive a tyrosine kinase inhibitor (TKI). The trial consists of two parts: the first part will enroll up to 34 patients who will receive radiation doses ranging from 24-60 Gy, followed by TKI therapy for those with actionable driver mutations. Patients will be monitored for disease progression every three months during TKI treatment.

Who should consider this trial

Good fit: Ideal candidates are treatment-naïve adults with metastatic, driver-mutated NSCLC and an identifiable primary lung lesion.

Not a fit: Patients who have previously received radiation therapy to the primary lung lesion or those with early-stage disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly extend the time patients live without disease progression.

How similar studies have performed: While there have been studies exploring radiation and TKI combinations, this specific approach in treatment-naïve, driver-mutated NSCLC is relatively novel.

Eligibility criteria

Inclusion Criteria Part 1

1. Age ≥18 years.
2. Patient must have a pathologically-confirmed diagnosis of non-small cell lung cancer (NSCLC).
3. An identifiable primary lung lesion must be present based on the consensus opinion of the medical oncology and radiation oncology investigators.
4. Patient did not previously receive radiation therapy to the primary lung lesion. Previous or concurrent palliative radiation to symptomatic metastatic lesions and definitive radiation to central nervous system metastases are allowable.
5. Patient must have advanced disease, either stage IV or stage IIIB/C that is not amenable to definitive multi-modality therapy.
6. Patient must not have received prior targeted therapy for NSCLC. A subject may receive up to 2 cycles of standard cytotoxic chemotherapy for NSCLC prior to trial enrollment. For example, a cycle of carboplatin and pemetrexed is given once every 3 weeks.
7. Patient must have measurable disease as defined by RECIST v1.1.
8. Patient must have Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
9. Ability to understand a written informed consent document, and the willingness to sign it.

Inclusion Criteria Part 2

1\. Must have an actionable driver mutation for which an Food and Drug Administration (FDA) -approved and/or National Comprehensive Cancer Network (NCCN) -recommended front-line TKI is available.

Exclusion Criteria:

1. Anticipated prognosis \< 3 months.
2. Inability to swallow oral medications or history of GI abnormality that would impair absorption of oral medications.
3. Patients with prior or concurrent malignancy are eligible provided the investigator assesses this malignancy does not have potential to interfere with evaluation of the safety or efficacy of the study treatments.
4. Patient must not have any unresolved toxicities from prior cancer therapy greater than CTCAE grade 2 at time of study enrollment. Any grade alopecia is allowable.
5. Patient must not have medical contraindications, as determined by treating radiation oncologist, that would preclude safe delivery of radiation therapy.
6. Women must not be pregnant or breast-feeding. All females of childbearing potential must have negative blood or urine pregnancy testing within 14 days of study enrollment.
7. Women of childbearing potential and sexually active males must use effective methods of contraception for 14 days prior to study enrollment, while on study treatment, and for 4 months after the last targeted therapy treatment.

Where this trial is running

Milwaukee, Wisconsin

• Froedtert Hospital & the Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Jonathan Thompson, MD, MS — Medical College of Wisconsin
• Study coordinator: Medical College of Wisconsin Cancer Center Clinical Trials Office

Conditions Non Small Cell Lung Cancer; non-small cell lung cancer; radiation therapy; tyrosine kinase inhibitor