Personalized Radiotherapy for Individualized Treatment Strategies and Monitoring (PRISM)

NCT07139990 | Recruiting Phase 1 DMC

• 1 other identifier: 20251050
• Study Type: interventional
• Target: 105
• 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; Thoracic Cancer; Sarcoma,Soft Tissue; HNPCC

Outcome Measures

Primary Outcomes (4)

• 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

• COHORT C- assess the rate of MWC in a novel approach of immunotherapy with concurrent PULSAR.

  Descriptive analyses will summarize the number and proportion of patients with MWCs, exact 95% confidence intervals, timing of MWCs relative to surgery, severity, management required, attribution to treatment, and whether each event occurred within the irradiated field. Given the small sample size and feasibility-oriented objective, analyses will be primarily descriptive rather than powered for formal hypothesis testing. Exploratory outcomes, including progression-free survival, pathologic response, immune correlates, and other clinical endpoints, will be summarized descriptively to inform future study design.

  5 years

• COHORT D-assess the proportion of patients who proceed to curative intent resection following neoadjuvant therapy.

  The primary endpoint is feasibility of the neoadjuvant radiotherapy and immunotherapy paradigm, defined as the proportion of patients who proceed to curative-intent surgical resection. Feasibility will be evaluated separately for each treatment arm, with particular focus on the PULSAR-IO arm. For each arm, the observed proportion proceeding to surgery will be summarized along with Exact (Clopper-Pearson) binomial confidence intervals. Feasibility will be declared if at least 90% of patients in the treatment arm proceed to curative-intent surgery. No formal hypothesis testing or between-arm comparisons are planned for the primary feasibility endpoint.

  5 years

Study Arms (4)

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)

COHORT C (Sarcoma Pre-operative PULSAR)

EXPERIMENTAL

Patients will receive pembrolizumab infusion every 3 weeks for three doses starting the day after the first pulse of radiation and then synchronizing the day after the administration of each pulse of radiation. Adjuvant pembrolizumab may be given at physician discretion per standard of care. External beam radiation will be delivered to a dose of 24 Gy in pulses of 8 Gy each once every 3 weeks over a total of 9 weeks. Surgery will be performed 3-6 weeks after cycle 3 of immunotherapy.

Radiation: Cohort C: Sarcoma Pre-Operative PULSAR

COHORT D (Resectable HNSCC PULSAR/SAbR):

EXPERIMENTAL

Random PULSAR or SAbR,by site.PULSAR:Each pulse of radiotherapy(RT)(8Gy)given to primary tumor/involved nodes using online adaptive RT plan.RT given 1-7 days before each pembrolizumab cycle,total of 3 pulses,3 weeks apart.Before 3rd pulse,repeat MRI \& PET simulation done.SAbR:Each fraction of RT(8 Gy)given to primary tumor/nodes using online adaptive RT plan.Total of 3 fractions of RT over 2 weeks,then 3 cycles of pembrolizumab done every 3 weeks.Both arms:adjuvant RT determined on surgical pathology \& risks of recurrence.Factors in primary tumor for adjuvant RT:pathologic T3/T4,positive/close(defined as \<3 mm)margins,lymphovascular invasion/perineural invasion.Factors in neck for adjuvant RT: \>1 lymph node,lymph nodes \>3 cm. Independent decision to treat primary site/lymph(either primary site/lymph treated based on criteria.)For adjuvant RT,primary site dose:60Gy in 30 fractions.Involved nodals:60Gy in 30 fractions.Uninvolved nodals:54Gy in 30 fractions.

Radiation: Cohort D: Resectable Head & Neck Squamous Cell Carcinoma (HNSCC) PULSAR/SAbR

Interventions

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

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):

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 C: Sarcoma Pre-Operative PULSAR RADIATION

Pre-operative PULSAR with immunotherapy for localized soft tissue sarcoma Adaptive Changes Allowed: Tumor target (size/shape)

COHORT C (Sarcoma Pre-operative PULSAR)

Cohort D: Resectable Head & Neck Squamous Cell Carcinoma (HNSCC) PULSAR/SAbR RADIATION

Neoadjuvant immunotherapy \& radiation given as either PULSAR (3 "pulses") or SAbR (3 fractions) prior to resection for HNSCC Adaptive Changes Allowed: Tumor and nodal target (size/shape)

COHORT D (Resectable HNSCC PULSAR/SAbR):

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 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.
• Cohort C:
• \>=18 years old
• Performance status ECOG 0-2
• Histologically confirmed surgically resectable, high grade (FNCLCC grade 2 or 3), localized soft tissue sarcoma of the trunk or extremities that measures \>5 cm in any direction as assessed by imaging

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
• Cohort C:
• Unresectable or metastatic (nodal or distant) disease
• Synchronous malignancy requiring chemotherapy or other intensive treatment
• Locally recurrent soft tissue sarcoma
• Prior immunotherapy
• Pregnancy or breastfeeding
• Cohort D:
• Distant metastasis
• Inability to undergo PET-CT for baseline staging

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; Sarcoma

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

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: 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 (size\>=2cm in brain or \>=1.5cm in brainstem) planned for fractionated stereotactic radiotherapy (fSRT) Cohort C: \>=18 yo with non-metastatic, resectable soft tissue sarcoma of trunk or extremity eligible for preoperative radiotherapy with concurrent immunotherapy Cohort D: \>=18 yo with newly diagnosed, resectable, stage III/IVA head and neck squamous cell carcinoma \* Please note that only Cohort D will be randomized into two groups, twenty patients to receive PULSAR and twenty patients to receive SAbR. Cohorts A, B and C are single arms with no randomization.

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: August 24, 2025
• Study Start: October 28, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2032
• Last Updated: August 17, 2026

Record last verified: 2026-08

Locations

US (1)