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

Phase 2

Not yet recruiting

• Conditions: Non Small Cell Lung Cancer
• Interventions: Device: Radiation Therapy; Drug: Targeted TKI therapy

• Registration Number: NCT06305715
• Lead Sponsor: Medical College of Wisconsin

Brief Summary

This prospective, two-part, single-arm, phase II trial is designed to evaluate whether the use of definitive radiation to the primary lung lesion prolongs progression-free survival (PFS) in treatment-naïve, metastatic, driver-mutated non-small cell lung cancers (NSCLC) patients who are subsequently placed on a tyrosine kinase inhibitor (TKI).

Detailed Description

This is a prospective, two-part, single-arm, phase II trial that will evaluate whether the use of definitive radiation to the primary lung lesion prolongs PFS in treatment-naïve, metastatic, driver-mutated NSCLC patients who are subsequently put on a TKI. Part 1 will enroll up to 34 patients who are are treatment-naïve and have metastatic NSCLC. Enrolled subjects will be given radiation doses, at the discretion of the treating physicians, that range from 24-60 Gy in 1-15 fractions with a minimum biologically effective dose (BED10) of 58 Gy.

Immediately following the completion of radiation therapy, patients who have an actionable driver mutation will be eligible to continue on to Part 2 of the study; those who do not meet the eligibility criteria for Part 2 will discontinue trial participation. Twenty-nine subjects will receive a standard-of-care targeted TKI therapy. The choice of TKI will be at the discretion of the treating oncologist, provided that their decision aligns with preferred TKIs per National Comprehensive Cancer Network (NCCN) guidelines. While on TKI therapy, patients will be assessed every three months for disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and survival.

Study Timeline

• Study First Submitted: 2024-03-05
• Study First Submitted QC: 2024-03-05
• Study First Posted: 2024-03-12
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-10
• Last Update Posted: 2024-05-13
• Study Start: 2024-07-15
• Primary Completion: 2027-06-15
• Study Completion: 2028-06-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiation therapy followed by mutation-matched TKI treatment	Radiation Therapy	Part 1 will enroll subjects who will be given radiation doses at the discretion of the treating physicians. Subjects with actionable driver mutation will continue to Part 2 and receive a standard-of-care TKI at the discretion of the treating oncologist.
Radiation therapy followed by mutation-matched TKI treatment	Targeted TKI therapy	Part 1 will enroll subjects who will be given radiation doses at the discretion of the treating physicians. Subjects with actionable driver mutation will continue to Part 2 and receive a standard-of-care TKI at the discretion of the treating oncologist.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	Start of TKI treatment to 18 months	The number of subjects without tumor progression based on RECIST v1.1 or death, whichever comes first. This will be measured from the start of TKI treatment until 18 months.

Trial Locations

Locations (1)

Froedtert Hospital & the Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States