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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating stage II and III non-small cell lung cancer using genomically guided radiation therapy (RT) alongside chemotherapy. The researchers aim to determine if personalizing radiation doses based on tumor genetics can increase effectiveness. Participants will be divided into groups receiving varying radiation doses, depending on their tumor profile. Individuals diagnosed with stage II or III non-small cell lung cancer that cannot be surgically removed might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 prior data suggests that genomically guided radiation therapy is safe for lung cancer patients?

Research has shown that genomically guided radiation therapy (RT) is under study to tailor cancer treatment to a tumor's genetic details. However, because this trial is in its early stages, limited information exists about its safety for people.

Early clinical trials typically aim to determine safe dosage levels and identify side effects. While this method appears promising, its safety in humans remains under investigation. Participants in these trials play a crucial role in understanding how well people tolerate these new treatments and whether they might cause any negative effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about genomically guided radiation therapy (RT) for lung cancer because it personalizes treatment based on each patient's tumor genetics. Unlike traditional RT, which typically administers a fixed dose to all patients, this innovative approach uses a genomic tool called the Radiosensitivity Index (RSI) to tailor the radiation dose. Arm A participants receive the standard 60 Gy dose, while Arm B's RSI-guided boost can increase the radiation up to 81 Gy, potentially enhancing treatment effectiveness. This tailored method could improve outcomes by optimizing radiation delivery to the tumor, minimizing damage to healthy tissue, and possibly reducing side effects.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will explore genomically guided radiation therapy (RT) for stage II and III non-small cell lung cancer (NSCLC). Participants will join different arms based on their genomic profile. Arm A will receive a standard RT dose of 60Gy, while Arm B will receive a higher dose, up to 81Gy, guided by genomic information. Arm C will receive the standard RT dose if genomic calculations are not possible. Research suggests that tailoring the radiation dose using a patient's unique genetic information could better control the tumor while reducing side effects. The genomic-adjusted radiation dose (GARD) has shown better results than traditional radiation by predicting how the cancer will respond to treatment. This approach aims to effectively treat cancer while causing less harm to healthy tissues. Early findings suggest that personalizing treatment in this way might be more effective than standard methods. ^{1 2 6 7 8}

Who Is on the Research Team?

Thomas Dilling, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05873439

Genomically Guided Radiation Dose Personalization in ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12384496/

Narrative Review of the Use of Genomic-Adjusted Radiation ... In multivariable analyses, GARD outperformed both the physical radiation dose and the underlying RSI in predicting outcomes such as distant ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8549863/

Personalizing Radiotherapy Prescription Dose Using ... This model simultaneously optimizes tumor control and toxicity by personalizing RT dose using patient-specific genomics. Results: Using data from two ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500223000016

Radiogenomics in lung cancer: Where are we? This review aims to present the current status of radiogenomics in lung cancer, integrating results obtained in association studies of SNPs.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04299

Genomically Guided Radiation Therapy for the ... This early phase I trial tests the feasibility of genomically guided radiation therapy (RT) with standard chemotherapy in treating patients with stage II-III ...

6. nature.com nature.com/articles/s41420-024-02270-2

Genomic predictors of radiation response: recent progress ... Here, we provide an overview of key mechanisms implicated in BM radiation resistance, including intrinsic and acquired resistance and intratumoral ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10669735/

Moving the Needle Forward in Genomically-Guided ... This summary is intended to provide practicing radiation oncologists, radiation biologists, and cancer genetics researchers an overview of the genetic basis of ...

8. onclive.com onclive.com/view/genomically-guided-radiation-dosing-model-shows-promise-in-various-cancer-types

Genomically-Guided Radiation Dosing Model Shows ... The genomic-adjusted radiation dose (GARD) model was a predictor for time to first recurrence and overall survival (OS) in patients with cancer who received ...