Pulse Radiotherapy for Lung Cancer

(PROMISE Trial)

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

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I study aims to evaluate the safety and effectiveness of adaptive pulsed radiotherapy combined with immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) resistant to immune checkpoint inhibitors. The primary goal is to assess treatment-related toxicity, while secondary objectives include progression-free survival, overall survival, and quality of life. The study will enroll 32 patients.

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 data supports the effectiveness of the treatment Pulse Radiotherapy for lung cancer?

Research on similar treatments, like hypofractionated radiotherapy, shows that it can improve survival and quality of life for lung cancer patients, especially when the tumor is controlled effectively. Studies have shown that intensive radiotherapy schedules can lead to better tumor control and increased survival rates. ^{1 2 3 4 5}

Is Pulse Radiotherapy generally safe for humans?

Pulsed low-dose rate radiation therapy has shown low rates of toxicity in studies, suggesting it may be generally safe for humans, although specific safety data for lung cancer is limited. ^{6 7 8 9 10}

How is Pulse Radiotherapy different from other treatments for lung cancer?

Pulse Radiotherapy is unique because it may involve delivering radiation in short, intense bursts, potentially allowing for more precise targeting of the tumor while minimizing damage to surrounding healthy tissue. This approach could differ from conventional radiotherapy techniques that often involve continuous radiation exposure. ^{11 12 13 14 15}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Outcomes of Modestly Hypofractionated Radiation for Lung Tumors: Pre- and Mid-Treatment Positron Emission Tomography-Computed Tomography Metrics as Prognostic Factors. [2018]

2. Italy pubmed.ncbi.nlm.nih.gov

[Radiotherapy as a single local regional treatment of non-oat cell carcinoma of the lung]. [2008]

3. England pubmed.ncbi.nlm.nih.gov

Is control of the primary tumour worthwhile in non-oat cell carcinoma of the bronchus? [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Hypofractionation in Early Stage Non-Small Cell Lung Cancer. [2022]

5. China pubmed.ncbi.nlm.nih.gov

Observation of the short-term therapeutic effect of 3D conformal hypofractionated single high-dose radiotherapy on lung tumors. [2006]

6. United States 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer: An In Vivo Animal Study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Pelvic Reirradiation Utilizing Pulsed Low-dose Rate Radiation Therapy. [2021]

9. Australia pubmed.ncbi.nlm.nih.gov

Phase I trials involving radiation therapy, quantifying the risks. [2013]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Defects in medical care delivery to patients with lung and breast cancer undergoing radiotherapy]. [2007]

11. France pubmed.ncbi.nlm.nih.gov

[Radiotherapy for non-small cell lung cancer]. [2009]

12. France pubmed.ncbi.nlm.nih.gov

[New techniques and potential benefits for radiotherapy of lung cancer]. [2016]

13. England pubmed.ncbi.nlm.nih.gov

Accelerated radical radiotherapy for non-small cell lung cancer using two common regimens: a single-centre retrospective study of outcome. [2018]

14. China pubmed.ncbi.nlm.nih.gov

The radiation techniques of tomotherapy & intensity-modulated radiation therapy applied to lung cancer. [2020]

15. England pubmed.ncbi.nlm.nih.gov

Predictors of respiratory-induced lung tumour motion measured on four-dimensional computed tomography. [2015]