Trial Outcomes & Findings for Radical RADiotherapy and Immunotherapy for Metastatic CAncer of the Lung (RRADICAL) (NCT NCT03176173)

Last Updated: 2025-11-05

Results Overview

Defined as percentage of participants without disease progression or death at 24 weeks from date of study entry, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): ≥30% decrease in the sum of the longest diameter of target lesions Overall Response (OR): CR + PR

Recruitment status

COMPLETED

Study phase

Target enrollment

45 participants

Primary outcome timeframe

24 weeks from study entry

Results posted on

2025-11-05

Participant Flow

Although the 'Immunotherapy Alone (Regular Medical Care)' arm was included in the study design, no participants were enrolled or assigned to this arm

Participant milestones

Participant milestones
Measure	Immunotherapy Plus Image-guided Radiation Therapy Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.	Immunotherapy Alone (Regular Medical Care) Patients who decline to undergo radiation therapy will continue their prior treatment with the treating physician's choice of regular medical care immunotherapy. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Overall Study STARTED	45	0
Overall Study COMPLETED	44	0
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Radical RADiotherapy and Immunotherapy for Metastatic CAncer of the Lung (RRADICAL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Immunotherapy Plus Image-guided Radiation Therapy n=44 Participants Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.	Immunotherapy Alone (Regular Medical Care) Patients who decline to undergo radiation therapy will continue their prior treatment with the treating physician's choice of regular medical care immunotherapy. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.	Total n=44 Participants Total of all reporting groups
Age, Customized 30-39 years	2 Participants n=15 Participants	—	2 Participants n=100 Participants
Sex: Female, Male Male	25 Participants n=15 Participants	—	25 Participants n=100 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=15 Participants	—	1 Participants n=100 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=15 Participants	—	43 Participants n=100 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=15 Participants	—	2 Participants n=100 Participants
Age, Customized 40-49 years	3 Participants n=15 Participants	—	3 Participants n=100 Participants
Age, Customized 50-59 years	4 Participants n=15 Participants	—	4 Participants n=100 Participants
Age, Customized 60-69 years	10 Participants n=15 Participants	—	10 Participants n=100 Participants
Age, Customized 70-79 years	18 Participants n=15 Participants	—	18 Participants n=100 Participants
Age, Customized 80-89 years	7 Participants n=15 Participants	—	7 Participants n=100 Participants
Sex: Female, Male Female	19 Participants n=15 Participants	—	19 Participants n=100 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=15 Participants	—	0 Participants n=100 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=15 Participants	—	0 Participants n=100 Participants
Race (NIH/OMB) Asian	15 Participants n=15 Participants	—	15 Participants n=100 Participants
Race (NIH/OMB) Black or African American	0 Participants n=15 Participants	—	0 Participants n=100 Participants
Race (NIH/OMB) White	26 Participants n=15 Participants	—	26 Participants n=100 Participants
Race (NIH/OMB) More than one race	0 Participants n=15 Participants	—	0 Participants n=100 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=15 Participants	—	1 Participants n=100 Participants
Region of Enrollment United States	44 participants n=15 Participants	—	44 participants n=100 Participants

PRIMARY outcome

Timeframe: 24 weeks from study entry

Outcome measures

Outcome measures
Measure	Immunotherapy Plus Image-guided Radiation Therapy n=43 Participants Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Progression-free Survival	26 Participants

SECONDARY outcome

Timeframe: Baseline (pre-treatment)

Population: Blood samples were collected for this outcome measure, however, no laboratory analysis was conducted due to lack of funding. No future analyses are planned.

Will correlate with radiographic response. Plasma biomarkers (e.g. cell free deoxyribonucleic acid level) will be summarized using medians and interquartile ranges; changes in biomarkers will be assessed using the Wilcoxon signed rank test. Correlation of biomarkers with radiographic response will be evaluated using a Wilcoxon rank sum test on patients with and without the event of interest. If feasible, these analyses will be supplemented by more formal analyses with the Cox model.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-radiation (up to 14 days before RT) and post-radiation (up to 14 days after completion of RT)

Population: Peripheral blood samples were collected at the pre-specified time points, but immune marker levels were not analyzed due to lack of funding for laboratory processing. No future analyses are planned.

Change in immune marker levels was measured using flow cytometry performed by the Human Immune Monitoring Core at Stanford University. These changes will correlate with radiographic response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 4 years after study entry

This outcome measured the number of participants who experienced Grade 3-5 acute (0-6 months) and late (\>6 months) toxicities, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4, through up to 4 years after study entry.

Outcome measures

Outcome measures
Measure	Immunotherapy Plus Image-guided Radiation Therapy n=44 Participants Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Number of Participants With Acute (0-6 Months) and Late (> 6 Months) Grade 3-5 Toxicity	4 Participants

SECONDARY outcome

Timeframe: Time from study entry to death, assessed up to 4 years after study entry

The electronic medical record was monitored for patient deaths.

Outcome measures

Outcome measures
Measure	Immunotherapy Plus Image-guided Radiation Therapy n=44 Participants Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Overall Survival	27.4 months Interval 20.37 to The upper bound of the 95% confidence interval could not be estimated due to an insufficient number of events at later time points.

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4 years

Number of participants who experienced a tumor response, including abscopal responses, following image-guided radiation therapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Immunotherapy Plus Image-guided Radiation Therapy n=44 Participants Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Number of Participants With Tumor Response (Including Abscopal Responses)	26 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-radiation (up to 14 days before RT) and post-radiation (up to 14 days after completion of RT)

Population: Imaging data were collected for assessment of progression-free survival using immune-related response criteria (iRRC); however, these data were not analyzed because the outcome was deemed not scientifically relevant at the time of final analysis. No future analyses are planned.

Evaluated with immune-related Response Criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4 years

Time to discontinuation of study immunotherapy agent was measured.

Outcome measures

Outcome measures
Measure	Immunotherapy Plus Image-guided Radiation Therapy n=44 Participants Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Time to Discontinuation of Study Immunotherapy Agent	6.1 Months Interval 2.7 to 12.8

Adverse Events

Immunotherapy Plus Image-guided Radiation Therapy

Serious events: 6 serious events

Other events: 32 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Immunotherapy Plus Image-guided Radiation Therapy n=44 participants at risk Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Respiratory, thoracic and mediastinal disorders Other - Respiratory distress	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Syncope	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Metabolism and nutrition disorders Hypokalemia	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Cough	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.3% 1/44 • Number of events 2 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Abdominal pain	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Abdominal distension	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Sepsis	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Nervous system disorders Stroke	2.3% 1/44 • Number of events 2 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Vascular disorders Hypertension	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Injury, poisoning and procedural complications Fracture	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Cardiac disorders Palpitations	2.3% 1/44 • Number of events 2 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Fever	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Other adverse events

Other adverse events
Measure	Immunotherapy Plus Image-guided Radiation Therapy n=44 participants at risk Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Image-guided Radiation Therapy: Ablative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. Immunotherapy (physician's choice for standard of care immunotherapy): Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Metabolism and nutrition disorders Anorexia	22.7% 10/44 • Number of events 12 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Cough	45.5% 20/44 • Number of events 24 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Esophagitis	18.2% 8/44 • Number of events 9 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Injury, poisoning and procedural complications Dermatitis radiation	15.9% 7/44 • Number of events 8 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Gastrointestinal disorders Mucositis oral	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Infections and infestations Papulopustular rash	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Toothache	2.3% 1/44 • Number of events 1 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
General disorders Fatigue	56.8% 25/44 • Number of events 36 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	31.8% 14/44 • Number of events 17 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Musculoskeletal and connective tissue disorders Other - Musculoskeletal pain	31.8% 14/44 • Number of events 22 • 4 years Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Additional Information

Clinical Associate Professor, Radiation Oncology - Radiation Therapy

Stanford University

Phone: (650) 723-6171

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place