Clinical trial NCT03176173: Radical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy
Official title: Radical RADiotherapy and Immunotherapy for Metastatic CAncer of the Lung (RRADICAL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Stage IV Non-Small Cell Lung Cancer
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2017-06-05
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well radical-dose image guided radiation therapy works in treating patients with non-small cell lung cancer that has spread to other places in the body who are undergoing immunotherapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radical-dose image guided radiation therapy to patients with non-small cell lung cancer may help to improve response to immunotherapy anti-cancer treatment.

Detailed description: PRIMARY OBJECTIVES:

I. Determine if progression-free survival at 24 weeks with this treatment combination is improved compared to historical controls who received immunotherapy without radiation therapy.

SECONDARY OBJECTIVES:

I. Assess acute (0-6 months) and late (\> 6 months) grade 3-5 toxicity. II. Assess overall survival. III. Correlate circulating tumor deoxyribonucleic acid (DNA) (ratio of post-radiation therapy \[RT\] to pre-RT level) with radiographic response.

IV. Correlate immune markers in peripheral blood with radiographic response.

TERTIARY OBJECTIVES:

I. Analyze progression-free survival with immune-related response criteria. II. Measure time to discontinuation of study immunotherapy agent. III. Assess patterns of progression.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while undergoing standard of care immunotherapy.

Arm II: Patients who decline to undergo radiation therapy receive standard of care immunotherapy.

After completion of study treatment, patients are followed up at 30 days and every 6 months thereafter.

Eligibility criteria: Inclusion Criteria:

1. Has stage IV non-small cell lung cancer, or initially stage I-III disease with distant metastatic recurrence
2. Age ≥ 18
3. Has been receiving anti-PD-1 or anti-PD-L1 immunotherapy for at least four weeks (refer to section 4.2.1)
4. Has had restaging imaging after initiation of immunotherapy, at least 4 weeks after pre-immunotherapy baseline imaging. CT or PET/CT of at least chest/upper abdomen must be performed within 4 weeks prior to registration. For patients with history of brain metastases, brain MRI or CT is required within 4 weeks of registration; for other patients brain MRI or CT is required within 12 weeks of registration. Diagnostic PET/CT performed as part of radiation simulation can be used as the restaging imaging.
5. Most recent imaging shows measurable disease as defined by RECIST 1.1
6. Evaluation by a Stanford medical oncologist must show:

   1. The patient is expected to continue on immunotherapy for at least three more months
   2. Imaging must show response, stable disease, or modest progression
   3. If there is modest progression, the patient must be clinically stable in terms of performance status and overall disease-related symptoms
7. Has at least one extracranial tumor safely treatable with radical-dose radiation therapy and that has not been previously treated with radiation
8. ECOG performance status 0-2
9. Has the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Untreated brain metastases, if not planned to be treated in this course of radiation therapy
* Pregnancy or women of childbearing potential not willing/able to use contraception during protocol treatment

Primary outcomes:
measure: Progression-free survival
timeFrame: At 24 weeks after study entry
Secondary outcomes:
measure: Change in circulating tumor deoxyribonucleic acid levels as measured using CAncer Personalized Profiling by deep Sequencing
timeFrame: Baseline up to 1 year after study entry
measure: Change in immune marker levels as measured from peripheral blood using flow cytometry performed by the Human Immune Monitoring Core at Stanford University
timeFrame: Baseline up to 1 year after study entry
measure: Incidence of acute (0-6 months) and late (> 6 months) grade 3-5 toxicity
timeFrame: Up to 4 years after study entry
measure: Overall survival
timeFrame: Time from study entry to death, assessed up to 4 years after study entry
Other outcomes:
measure: Patterns of response and progression
timeFrame: Up to 4 years
measure: Progression free survival
timeFrame: Up to 4 years
measure: Time to discontinuation of study immunotherapy agent
timeFrame: Up to 4 years
Locations:
city: Palo Alto
country: United States
facility: Stanford University, School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Michael Gensheimer
role: PRINCIPAL_INVESTIGATOR
References: