Personalized Radiotherapy for Individualized Treatment Strategies and Monitoring (PRISM)

NCT07139990 | Recruiting Phase 1 DMC

• 1 other identifier: 20251050
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

To characterize feasibility, safety, and/or preliminary efficacy of personalized strategies to adapt standard radiotherapy treatments to individual patient responses.

Conditions

Small Cell Lung Cancer Extensive Stage; Brain Metastases; Solid Tumor, Adult

Outcome Measures

Primary Outcomes (2)

• COHORT A-assess safety of addition of PULSAR radiotherapy to thoracic tumor in ES-SCLC alongside chemoimmunotherapy, while making preliminary/exploratory assessments of disease response and dosimetric benefit to PULSAR

  Primary objective will be to report safety of PULSAR with chemoimmunotherapy for extensive stage small cell lung cancer. Accrual goal will be 15 patients.Study is interested in precise estimates of safety as well as outcome variability that will aid in the planning of larger, sufficiently powered efficacy trial. Sample size of 15 patients will allow for relative precision in conclusions regarding safety outcome.Namely,if 4 out of 15 patients enrolled are observed as having grade 3+ cardiopulmonary acute toxicity,the 95% CI for that rate would be (7.95%-55.10%) using an Exact (Clopper-Pearson) binomial confidence interval. Descriptive statistics according to variable type (continuous, categorical) will be used for reporting the cohort characteristics. Primary endpoint of pre-defined high grade toxicities will be reported as a categorical percentage.Disease control(time to event variables) will be reported by Kaplan-Meier estimates.

  5 years

• COHORT B-assesses ability to de-escalate dose in good responders by imaging using rule-based imaging-response guided omission of 2nd "pulse" of PULSAR fractionated SRS (fSRS) for brain metastases

  Sample size comparing local control \& toxicity with prior PULSAR data(which didn't dose de-escalate based on response)to ensure high control rate is preserved.Using two-tailed test with alpha of 0.05 \& power of 0.8,estimated sample size to detect difference in 1-yr local failure rates between pSRT \& fSRT.Stats according to variable type(continuous,categorical)used for reporting primary endpoint of proportion of patients de-escalated \& endpoints.To evaluate local control \& toxicity(late CNS),competing risk regression \& calculated cumulative incidence,with death as competing risk will be performed.Gray's test will be used to assess statistical significance.OS analyzed using Kaplan-Meier method using survival,log-rank test employed to compare survival distributions.To account for clustered data,where patients may have multiple brain metastases treated,repeated analyses for CRR using crrSC(R package)will be performed.

  5 years

Study Arms (2)

COHORT A (ES-SCLC PULSAR Thoracic Tumor):

EXPERIMENTAL

PULSAR with online adaptive planning to 7-10 Gy per fraction for up to 3 pulses directed at the bulkiest sites of disease in the thorax before infusion days (window: D-1 to D-4; optimal D-1) of three cycles of chemoimmunotherapy. The first radiotherapy pulse must be delivered before chemoimmunotherapy cycle 4. The three "pulses" of radiotherapy ideally should be given with consecutive cycles of systemic therapy. Radiotherapy can be suspended if a complete clinical response is reached before all 3 pulses are delivered. Chemoimmunotherapy will be given per standard of care

Radiation: Cohort A: Extensive Stage Small Cell Lung Cancer (ES-SCLC) Thoracic Tumor PULSAR (Personalized ultrahypofractionated stereotactic ablative radiotherapy)

COHORT B (Brain metastasis PULSAR):

EXPERIMENTAL

PULSAR will be delivered in a 2 "pulse" strategy: 1: Deliver fSRT/SRS every other day (minimum 48 hour separation between treatments, minimum 1 treatment per week;begin and complete within 60 days of registration) for 3 fractions. Pulse 1 must begin and complete within 60 days of registration; 2) Repeat treatment planning MRI will be performed after 4 weeks (window: +/-1 weeks) after fraction 3 and volumetric response assessment made; 3) Pulse 2 is omitted in those with \>=25% volumetric size reduction response. In others, pulse 2 will deliver fSRT/SRS every other day (minimum 48 hour separation between treatments, minimum 1 treatment per week). Pulse 2 may deliver higher dose per fraction within Section 4.1.3.4 specifications (Table 6), rationale for this would be for addressing lesions that either due to large size or proximity to critical structures could only be treated to a lower dose range in pulse 1. Pulse 2 must begin 4 weeks (+/-1 weeks) after end of Pulse 1.

Radiation: Cohort B: Brain metastasis PULSAR (Personalized ultrahypofractionated stereotactic ablative radiotherapy)

Interventions

Cohort A: Extensive Stage Small Cell Lung Cancer (ES-SCLC) Thoracic Tumor PULSAR (Personalized ultrahypofractionated stereotactic ablative radiotherapy) RADIATION

Radiographic response-adapted thoracic tumor radiotherapy given as single doses ('pulses') before standard of care chemoimmunotherapy cycles. Adaptive Changes Allowed: Tumor target (size/shape), # of doses (reduction) Adaptive Changes Allowed: Tumor target (size/shape), # of doses (reduction)

COHORT A (ES-SCLC PULSAR Thoracic Tumor):

Cohort B: Brain metastasis PULSAR (Personalized ultrahypofractionated stereotactic ablative radiotherapy) RADIATION

Intervention: Fractionated stereotactic radiosurgery (SRS, 5 doses total) for brain metastasis given in two "pulses" (3 fractions + 2 fractions) with second pulse adapted to interim radiographic response Adaptive Changes Allowed: Omission of 2nd "pulse" in \>=25% responders or tumor target size/shape change in remainder

COHORT B (Brain metastasis PULSAR):

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort A:
• \>=18 years old
• Performance status ECOG 0-2
• Extensive stage small cell lung cancer diagnosed by tissue biopsy within 180 days of registration.
• Patient must be planned for or receiving standard of care chemoimmunotherapy.
• Patient must have received no more than 3 cycles by time of study enrollment.
• Able and indicated according to investigator to receive thoracic radiotherapy
• Cohort B:
• years old
• Diagnosis of solid tumor malignancy with MRI-defined brain metastasis lesions (1-5 lesions allowed) within 60 days of registration
• Each brain metastasis lesion enrolled must be 2 - 5 cm, except brainstem lesions which may be 1.5 - 5cm in size.

You may not qualify if:

• Cohort A:
• ⨀ Prior thoracic Radiotherapy
• Cohort B:
• Prior whole brain Radiotherapy
• Prior surgical resection or focal radiotherapy of a target brain metastasis
• Leptomeningeal disease

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

Ut Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• NEIL DESAI, MD, MHS

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

SARAH NEUFELD

CONTACT

214 648 1836; Sarah.Hardee@UTSouthwestern.edu

NEIL DESAI, MD, MHS

CONTACT

214 648 1836; Neil.Desai@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: n/a No radiotherapy will be given aside from standard of care. However, this study will focus on compressing the time frame in which said therapy is administered.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD MHS

Model Details: Cohort A: \>= 18 yo with extensive stage small cell lung cancer receiving standard chemoimmunotherapy and eligible for thoracic radiotherapy Cohort B: \>= 18 yo with solid tumor brain metastases (\<=5 total; size\>=2cm in brain or \>=1.5cm in brainstem) planned for fractionated stereotactic radiotherapy (fSRT)

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: August 24, 2025
• Study Start: October 28, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2030
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (1)