Personalized Radiotherapy for Small Cell Lung Cancer and Brain Tumors

(PRISM Trial)

Overseen By NEIL DESAI, MD, MHS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Chemoimmunotherapy

Disqualifiers: Prior radiotherapy, Leptomeningeal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a personalized approach to radiotherapy for small cell lung cancer and brain tumors. The goal is to determine if tailoring radiotherapy to individual patient responses is safe and effective. Participants are divided into two groups: one for patients with small cell lung cancer in the chest and another for those with brain tumors. Suitable candidates include individuals with extensive-stage small cell lung cancer currently undergoing chemoimmunotherapy or those with 1-5 brain tumor spots detected by an MRI. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that personalized ultrahypofractionated stereotactic ablative radiotherapy is safe?

Previous studies have shown promising safety results for a new type of focused, high-dose radiation treatment for both lung tumors and brain metastases. While researchers continue to learn about its safety for lung tumors, it has been successfully used in some cases, particularly for tumors in central lung areas, with few serious side effects reported.

For brain metastases, early findings suggest that patients generally tolerate this treatment well, experiencing few severe side effects. The treatment targets tumors precisely, protecting healthy tissue. This precision reduces side effects and may improve treatment success.

As this is a new approach, ongoing research remains crucial to fully understand its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the personalized ultrahypofractionated stereotactic ablative radiotherapy (PULSAR) for small cell lung cancer and brain tumors because it offers a more tailored approach to treatment. Unlike traditional radiotherapy, which often involves a standard treatment plan, PULSAR uses online adaptive planning to customize doses specifically for the patient's tumor characteristics. This allows for higher precision in targeting the cancerous tissue, potentially leading to fewer side effects and better outcomes. Additionally, the ability to adapt the treatment based on the tumor's response means that therapy can be adjusted in real-time, making it more effective and efficient. Overall, PULSAR represents a significant advancement in personalizing cancer treatment.

What evidence suggests that personalized radiotherapy could be effective for small cell lung cancer and brain tumors?

Research has shown that a new type of personalized radiation therapy, called PULSAR, may effectively treat small cell lung cancer and brain tumors. In this trial, participants with small cell lung cancer will receive PULSAR targeting large tumor areas in the lung, especially when combined with chemoimmunotherapy. This approach quickly shrinks tumors with each treatment. Meanwhile, participants with brain tumors will receive PULSAR to control tumor growth, with early research indicating it can do so with few side effects. This personalized method aims to adjust treatments based on each patient's response, potentially making it safer and more effective. ^{1 4 6 7 8}

Who Is on the Research Team?

NEIL DESAI, MD, MHS

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

The PRISM trial is for adults with small cell lung cancer or brain tumors who are undergoing standard chemoimmunotherapy. They must have started treatment within three cycles, be able to receive thoracic radiotherapy, and have a performance status showing they can carry out daily activities. Brain tumor patients should have 1-5 lesions suitable in size.

Inclusion Criteria

I am planned for or currently receiving standard chemoimmunotherapy.

I am 18 years old or older.

I have 1-5 brain tumors identified by MRI in the last 60 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Cohort A

PULSAR radiotherapy with chemoimmunotherapy for ES-SCLC, with up to 3 pulses of radiotherapy before infusion days of three cycles of chemoimmunotherapy.

Approximately 12-18 weeks

Multiple visits for radiotherapy and chemoimmunotherapy cycles

Treatment - Cohort B

PULSAR radiotherapy for brain metastases with a 2 pulse strategy, including fSRT/SRS treatments and interim imaging for response assessment.

Up to 8 weeks

Multiple visits for radiotherapy and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Personalized ultrahypofractionated stereotactic ablative radiotherapy

Trial Overview This study tests personalized ultrahypofractionated stereotactic ablative radiotherapy (PULSAR) on two groups: one with extensive stage small cell lung cancer affecting the chest area, and another with brain metastasis. It aims to adapt radiation therapy based on individual patient responses.

How Is the Trial Designed?

Group I: COHORT B (Brain metastasis PULSAR): Experimental Treatment 1 Intervention

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.

Group II: COHORT A (ES-SCLC PULSAR Thoracic Tumor): Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06712745

Feasibility Study of Personalized Ultra-fractionated ... The objective of this study is to enhance the safety profile of SAbR in ultra-central tumors of the lung (primary or metastatic) without compromising its ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10502697/

Individualized Stereotactic Ablative Radiotherapy for Lung ... This nonrandomized controlled trial of patients diagnosed with non–small cell lung cancer assesses whether individualizing stereotactic ablative radiotherapy ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07139990

Personalized Radiotherapy for Individualized Treatment ... In seeking to address this, this study notes that small cell lung cancer generally shrinks rapidly with each cycle of chemoimmunotherapy. Delivering a "pulse" ...

4. utswmed.org utswmed.org/cancer/cancer-answers/pulsar-paradigm-for-effective-radiotherapy/

PULSAR: A Paradigm for Safer, More Effective ... A new approach to radiation therapy that abandons classic daily fractions is now being investigated in rectal, brain, and lung cancer ...

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2823972

Stereotactic vs Hypofractionated Radiotherapy for ... In this randomized clinical trial, SBRT resulted in acceptable tumor control compared with CRT with limited toxic effects.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9118536/

Safety and Efficacy of Stereotactic Ablative Radiotherapy for ... Stereotactic ablative radiotherapy (SABR) or stereotactic body radiotherapy (SBRT) obviously improved the clinical efficacy and survival of UCLC patients.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1556086419303156

Safety and Effectiveness of Stereotactic Ablative ... The safety and effectiveness of stereotactic ablative radiotherapy (SABR) in patients with ultra-central lung tumors is currently unclear.

8. redjournal.org redjournal.org/article/S0360-3016(24)00480-2/fulltext

Stereotactic Radiation for Ultra-Central Non-Small Cell ... The goals of this study were to determine the maximum tolerated dose (MTD) of SBRT and to assess treatment-related toxicity, oncologic outcomes, ...