Genomic-Guided RT for Lung Cancer

Overseen By Thomas Dilliing, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants

Disqualifiers: Pregnancy, Brain metastases, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 30

Duration: 12 weeks

3 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to determine the feasibility of genomically guided radiation therapy (RT) with concurrent chemotherapy in the management of stage II and III non-small cell lung cancer (NSCLC).

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medication within 14 days before starting the study treatment, with some exceptions like certain steroids.

What data supports the effectiveness of the treatment Genomically Guided Radiation Therapy (RT) for lung cancer?

Research shows that consolidative radiotherapy (RT) can improve overall survival in patients with oligometastatic non-small cell lung cancer, suggesting that targeted radiation treatments like Genomically Guided RT may also be effective. ^{1 2 3 4 5}

Is genomic-guided radiation therapy generally safe for humans?

The safety of combining radiation therapy with immune treatments has been studied, showing some risks of side effects, but these studies focused on lung cancer and not specifically on genomic-guided radiation therapy. The available data suggest that combining these treatments can lead to adverse events, but more research is needed to understand the safety of genomic-guided radiation therapy specifically. ^{6 7 8 9 10}

How is Genomically Guided Radiation Therapy different from other treatments for lung cancer?

Genomically Guided Radiation Therapy for lung cancer is unique because it uses genetic information to tailor the radiation treatment specifically to the patient's tumor, potentially improving effectiveness and reducing side effects compared to standard radiation therapy. ^{1 2 11 12 13}

Research Team

Thomas Dilling, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

Adults diagnosed with stage II or III non-small cell lung cancer (NSCLC) who are in good physical condition (ECOG 0-1), have a life expectancy over 12 weeks, and can provide a fresh tumor biopsy. Prior treatments are allowed. Participants must not be pregnant, breastfeeding, or have had certain other cancers within the last two years. They should not be on immunosuppressive medications recently and must agree to use effective contraception.

Inclusion Criteria

I have recovered from recent surgery and my surgeon has cleared me.

My lung cancer is at Stage 2 or 3 and cannot be removed by surgery.

My lung cancer type has been confirmed with a recent biopsy.

Exclusion Criteria

I have recovered from any major surgery or significant injury at least 14 days before starting the study drug.

I have cancer that has spread to my brain or the lining around my brain.

I haven't taken strong immune-weakening medicines in the last 14 days, except for minor exceptions like nasal sprays or low-dose steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive genomically guided radiation therapy with concurrent chemotherapy

12 weeks

30 visits (in-person for radiation fractions)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term follow-up

Participants are monitored for overall survival and freedom from local regional progression

2 years

Treatment Details

Interventions

• Genomically Guided Radiation Therapy (RT)

Trial Overview The trial is testing personalized radiation therapy guided by genomic information alongside standard chemotherapy for patients with locally advanced NSCLC. The goal is to see if this tailored approach is feasible and beneficial compared to traditional methods.

Participant Groups

Group I: Arm C: unable to calculate RSI Experimental Treatment 1 Intervention

Participants in will receive standard RT dose of 60Gy in 30 fractions targeting the primary tumor and any involved regional lymph nodes.

Group II: Arm B: RSI predicts dose > 60 Gy Experimental Treatment 1 Intervention

Participants will receive treatment with RxRSI guided boost to the primary tumor up to 81Gy (2.7Gy/fraction).

Group III: Arm A: RSI predicts dose ≤ 60 Gy Experimental Treatment 1 Intervention

Participants will receive standard RT dose of 60Gy in 30 fractions targeting the primary tumor and any involved regional lymph nodes.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Findings from Research

In a study of 79 patients receiving both immune checkpoint inhibitors and thoracic radiation therapy, the rates of significant adverse events (Grade ≥2) such as pneumonitis, esophagitis, and dermatitis were found to be acceptable and consistent with expectations.

There was no significant difference in the rates of adverse events between patients receiving concurrent (within 1 month) versus sequential (up to 6 months apart) treatments, indicating that concurrent therapy may be a safe option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition. von Reibnitz, D., Chaft, JE., Wu, AJ., et al.[2022]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Evaluating single-institution resource costs of consolidative radiotherapy for oligometastatic non-small cell lung cancer using time-driven activity-based costing. [2022]

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

Radiotherapy alone versus radiochemotherapy in patients with stage IIIA adenocarcinoma (ADC) of the lung. [2021]

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

Radiotherapy alone vs. radiochemotherapy in patients with favorable prognosis of clinical stage IIIA non-small-cell lung cancer. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Sequential or concomitant chemotherapy in limited stage small-cell lung cancer. [2018]

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

Clinical Outcomes of the HIV Protease Inhibitor Nelfinavir With Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer: A Phase 1/2 Trial. [2022]

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

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition. [2022]

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

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Related to the Timing of Radiotherapy and Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer: A Single Institutional Experience. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Impact of EGFR mutations and KRAS amino acid substitution on the response to radiotherapy for brain metastasis of non-small-cell lung cancer. [2018]

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

Conventional radiographic follow-up in the irradiated lung. [2022]

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

Personalized Radiation Therapy (PRT) for Lung Cancer. [2016]

13. Ireland pubmed.ncbi.nlm.nih.gov

ICORG 06-35: a prospective evaluation of PET-CT scan in patients with non-operable or non-resectable non-small cell lung cancer treated by radical 3-dimensional conformal radiation therapy: a phase II study. [2020]