Pulse Radiotherapy for Lung Cancer

(PROMISE Trial)

Not yet recruiting at 1 trial location

Overseen By Houda Bahig, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Houda Bahig

Must be taking: PD(L)-1 inhibitors

Disqualifiers: Pregnancy, Pneumonitis, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat lung cancer that has spread and resists current medicine. It combines a targeted radiation therapy, called Pulse Radiotherapy, with drugs that enhance the immune system's ability to fight cancer. The primary goal is to assess the safety and effectiveness of this approach in controlling cancer. Suitable candidates have non-small cell lung cancer that continues to grow despite treatment, affecting five or more areas in the body. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that if you are on additional systemic therapy agents like chemotherapy, these should be temporarily stopped during radiation treatment.

What prior data suggests that this treatment is safe?

Research has shown that pulsed low-dose rate radiation therapy, such as pulse radiotherapy, usually has low toxicity, making it generally safe for people. Although specific safety data remains limited, early studies suggest that patients tolerate this treatment well. Additionally, combining radiation with immunotherapy may effectively treat lung cancer. In some studies, this combination has shown promise in shrinking tumors without causing severe side effects. Overall, evidence suggests that pulse radiotherapy could be a safe option for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pulse Radiotherapy is unique because it combines pulsed radiotherapy with PD(L)-1 inhibitors to specifically target 2 to 5 progressive extracranial lesions per cycle. This approach differs from standard treatments like conventional radiotherapy or chemotherapy, which often affect a broader area and can lead to more side effects. Researchers are excited about this treatment because it promises a more precise attack on cancer cells, potentially leading to fewer side effects and better outcomes for patients with lung cancer. By harnessing the body's immune response with PD(L)-1 inhibitors, it offers a novel mechanism that could enhance the effectiveness of radiotherapy.

What evidence suggests that pulse radiotherapy might be an effective treatment for metastatic non-small cell lung cancer?

Research has shown that pulse radiotherapy combined with immunotherapy might help patients with advanced non-small cell lung cancer (NSCLC) live longer and slow disease progression. This trial will examine the effects of pulse radiotherapy with PD(L)-1 inhibitors. Early studies suggest this combination could improve both the time patients live without cancer progression and their overall survival. In one report, a patient's cancer completely disappeared after treatment with pulse radiotherapy and a specific immunotherapy drug. Another study found that adding chest radiotherapy can extend the lives of lung cancer patients. Although more research is needed, these findings suggest that pulse radiotherapy could be a promising treatment for those who do not respond to current therapies. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with advanced non-small cell lung cancer (NSCLC) that hasn't responded to immune checkpoint inhibitors. Participants should be adults who can handle repeated radiotherapy sessions and are willing to combine this treatment with immunotherapy.

Inclusion Criteria

Ability to provide written informed consent

I have brain metastasis and am receiving standard treatment for it.

I am able to get out of my bed or chair and move around.

Exclusion Criteria

Presence of an active autoimmune disease

Pregnant or breastfeeding individuals are excluded

I have never had pneumonitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy

Pulsed radiotherapy combined with PD(L)-1 inhibitors targeting 2 to 5 progressive extracranial lesions per cycle

Up to 3 cycles

Multiple visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pulse Radiotherapy

Trial Overview

The study tests adaptive pulsed radiotherapy alongside immunotherapy in patients whose NSCLC has resisted previous treatments. The main focus is on how safe the treatment is, but it will also look at how long patients live without their cancer getting worse, overall survival, and life quality.

How Is the Trial Designed?

Group I: Pulse Radiotherapy Experimental Treatment 1 Intervention

Pulsed radiotherapy combined with PD(L)-1 inhibitors targeting 2 to 5 progressive extracranial lesions per cycle

Who Is Running the Clinical Trial?

Houda Bahig

Lead Sponsor

Trials

2

Recruited

90+

Varian, a Siemens Healthineers Company

Industry Sponsor

Trials

35

Recruited

7,200+

Published Research Related to This Trial

In a review of 98 phase I radiation therapy trials involving 2994 patients, there were significant risks associated with treatment, including 33 treatment-related deaths and 1812 cases of acute grade 3/4 toxicities, resulting in a median toxicity ratio of 0.46.

Trials that included chemotherapy showed a notably higher toxicity ratio (0.60) compared to those without chemotherapy (0.08), indicating that combining chemotherapy with radiation therapy increases the risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trials involving radiation therapy, quantifying the risks. Lawrence, YR., Glass, C., Symon, Z., et al.[2013]

In a study of 1361 patients undergoing radiation therapy for locally advanced lung cancer, over half (53%) reported significant declines in their quality of life (QoL) by the end of treatment, indicating that treatment can have a substantial impact on patient well-being.

While clinician-reported adverse events (AEs) were linked to declines in QoL, the correlation was only moderate, suggesting that patient-reported outcomes (PROs) are crucial for understanding the full impact of treatment and may help identify when interventions are needed to improve patient experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Physician- and Patient-Reported Symptoms in Patients Treated With Definitive Radiation Therapy for Locally Advanced Lung Cancer in a Statewide Consortium. Wilkie, JR., Hochstedler, KA., Schipper, MJ., et al.[2022]

Concurrent chemoradiation is the standard treatment for locally advanced unresectable non-small-cell lung cancer, highlighting its efficacy as a major therapeutic option.

New radiotherapy techniques, such as respiratory gating and intensity-modulated radiotherapy, are being developed to improve treatment precision, while stereotactic and proton-beam therapies may offer better options for early-stage tumors in non-operable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy for non-small cell lung cancer]. Girard, N., Mornex, F.[2009]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06622174

Pulse Radiotherapy to Overcome Metastatic Immune ...

This phase I study aims to evaluate the safety and effectiveness of adaptive pulsed radiotherapy combined with immunotherapy in patients with metastatic non- ...

2.

withpower.com

withpower.com/trial/phase-1-metastatic-lung-cancer-3-2025-4f6ac

Pulse Radiotherapy for Lung Cancer (PROMISE Trial)

In a study of 1361 patients undergoing radiation therapy for locally advanced lung cancer, over half (53%) reported significant declines in their quality of ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12433100/

Survival outcomes of thoracic radiotherapy in addition to ...

Over half of the lung cancer patients present with metastasis at the initial diagnosis (2), among which 80–85% are histologically subclassified ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0169500225004672

Early experience with PEF in the setting of recalcitrant ...

This study suggests that PEF therapy may be associated with significantly improved PFS and OS in patients with progressive stage IV non-small cell lung cancer.

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frontiersin.org

frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.737425/full

Pulsed Radiation Therapy to Improve Systemic Control of ...

One case report of a patient with non-small cell lung cancer (NSCLC) who experienced a complete response to RT and CTLA4 blockade ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9582356/

Pulsed radiotherapy to mitigate high tumor burden and ...

Preclinical evidence suggests radiation and immunotherapies are synergistic in treating non-small cell lung cancer and other solid tumors (36, ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0167814022002341

Multi-institutional phase II study on the safety and efficacy ...

This study aimed to evaluate the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy (DTT-SBRT) for lung tumors.

8.

cco.amegroups.org

cco.amegroups.org/article/view/139535/html

Pulsed reduced dose rate radiotherapy: a narrative review - Atak

Notably, PRDR significantly reduced normal tissue toxicity, evidenced by less weight loss (25.69±1.27 vs. 20.94±1.68 g) and extended survival times (12 vs. 8 ...