PLDR + Chemotherapy for Lung Cancer

Overseen By Joshua E. Meyer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fox Chase Cancer Center

Must be taking: Carboplatin-Paclitaxel

Disqualifiers: Previous thorax radiotherapy, Radiation hypersensitivity, Scleroderma, others

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

Compensation: Varies

Number of Visits: 1

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation, called Pulsed Low Dose Radiation (PLDR), alongside chemotherapy for treating non-small cell lung cancer and esophageal cancer. The goal is to determine if PLDR can reduce the risk of severe esophagitis (painful swelling in the esophagus) that often occurs with standard treatments, while maintaining effectiveness against the cancer. This trial suits individuals who have not yet received treatment and have either Stage IIIA non-small cell lung cancer or localized esophageal cancer. Participants will receive PLDR radiation with the chemotherapy drugs Carboplatin and Paclitaxel. 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 protocol does not specify whether you need to stop taking your current medications. However, since the trial involves concurrent chemoradiation with Carboplatin-Paclitaxel, it's best to discuss your current medications with the trial team to ensure there are no interactions.

What prior data suggests that the Pulsed Low Dose Radiation technique is safe for use with chemotherapy?

Research has shown that Pulsed Low Dose Radiation (PLDR) might be safer than traditional radiation for some cancers. In a previous study, researchers used PLDR on patients who had already received radiation treatment. The study found PLDR to be safe for these patients, particularly concerning short-term side effects. However, because the study focused on patients with a short life expectancy, information on long-term safety remains limited.

Promising data also exist regarding the use of PLDR with the chemotherapy drugs carboplatin and paclitaxel. One study indicated that this combination could effectively treat advanced lung cancer. While the study does not provide detailed safety data, it suggests that the treatments are generally well-tolerated together.

Overall, PLDR and the chemotherapy drugs carboplatin and paclitaxel have shown potential for safety and effectiveness. However, as this trial is in the early stages, further research is needed to confirm long-term safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of Pulsed Low Dose Radiation (PLDR) with Carboplatin and Paclitaxel for lung cancer because it introduces a unique approach to treatment. Unlike traditional therapies that use continuous radiation, PLDR administers radiation in short bursts, potentially reducing damage to healthy tissue while effectively targeting cancer cells. This method could enhance the effectiveness of well-known chemotherapy agents like Carboplatin and Paclitaxel, offering a potentially safer and more efficient treatment option for lung cancer patients.

What evidence suggests that Pulsed Low Dose Radiation with chemotherapy could be effective for lung cancer?

Research has shown that Pulsed Low Dose Radiation (PLDR), administered alongside Carboplatin and Paclitaxel in this trial, can effectively control tumors with fewer side effects than traditional radiation. Studies have found that PLDR, when combined with common chemotherapy drugs like Carboplatin and Paclitaxel, remains effective in shrinking tumors. Experiments demonstrated that PLDR significantly slows tumor growth and improves survival in animal studies. Additionally, earlier research noted that PLDR reduces damage to healthy tissue, potentially leading to fewer side effects such as severe esophagitis, a painful swelling of the esophagus. This makes PLDR a promising method for treating cancers like non-small cell lung cancer while minimizing harm to patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Joshua E. Meyer

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with untreated non-small cell lung cancer (Stage IIIA) or localized esophageal cancer, who can undergo chemotherapy with Carboplatin-Paclitaxel followed by surgery. They must be in good physical condition (ECOG 0-1), able to read/write English for questionnaires, meet specific lab criteria for blood and organ function, use effective birth control, and consent to study procedures.

Inclusion Criteria

I am older than 18 years.

Patients must be able to read and write English to comply with the questionnaire portions of the protocol

I have untreated Stage IIIA non-small cell lung cancer or localized esophageal cancer.

Exclusion Criteria

You have a history of scleroderma or other ongoing connective tissue disease.

I have a history of extreme sensitivity to radiation or ataxia telangiectasia.

I am not pregnant, not breastfeeding, and if of childbearing age, have a recent negative pregnancy test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pulsed Low Dose Radiation concurrent with Carboplatin and Paclitaxel

3 months

Monthly visits for chemotherapy and radiation sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Surveys conducted at 1st, 2nd, 3rd, 6th, 9th, and up to 12th month

Long-term follow-up

Progression free survival will be evaluated from the day of first treatment until disease progression

1-5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pulsed Low Dose Radiation

Trial Overview This Phase I trial tests Pulsed Low Dose Radiation (PLDR) combined with chemotherapy (Carboplatin-Paclitaxel) against severe acute esophagitis in patients with lung or esophageal cancer. PLDR aims to reduce side effects compared to conventional radiation while maintaining treatment effectiveness.

How Is the Trial Designed?

Group I: Pulsed Low dose radiation with Carboplatin/Paclitaxel Experimental Treatment 3 Interventions

Pulsed Low Dose Radiation concurrent with Carboplatin and Paclitaxel

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

A phase II study involving 32 patients with advanced non-small cell lung cancer showed that combining paclitaxel with carboplatin and radiotherapy is feasible and has acceptable toxicity levels, with no grade 4 toxicities reported.

While some patients experienced grade 3 neutropenia and mucositis, the study indicates that this combined treatment approach could improve outcomes, and further research is needed to optimize dosages and treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease. Belani, CP., Aisner, J., Bahri, S., et al.[2015]

Induction chemotherapy with paclitaxel and carboplatin, followed by concurrent chemoradiation, showed a 55% response rate and a 1-year survival rate of 72% in patients with locally advanced non-small cell lung cancer, indicating promising efficacy.

The treatment regimen was well-tolerated, with mild myelotoxicity as the primary side effect from induction therapy and limited nonhematologic toxicity during concurrent therapy, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer. Langer, CJ.[2015]

In a Phase I trial involving 20 patients with inoperable non-small cell lung cancer (NSCLC), a weekly regimen of paclitaxel (up to 90 mg/m²) combined with carboplatin was found to be well tolerated, with no maximum-tolerated dose reached.

The treatment resulted in a response rate of 35% and a median survival of 11.1 months, indicating that this weekly schedule is a viable alternative to the standard every-3-week protocol for patients with untreated inoperable NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer: JCOG 9910-DI. Naoki, K., Kunikane, H., Fujii, T., et al.[2015]

In a Phase I/II clinical trial involving 41 patients with non-small cell lung cancer, pulsed low-dose paclitaxel combined with radiation achieved a remarkable 100% tumor response rate and an average tumor shrinkage of 83%.

The treatment demonstrated low toxicity, with only a few cases of grade 3 pneumonitis and esophagitis, making it a promising option for patients who may not tolerate standard chemoradiation regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II clinical study of pulsed paclitaxel radiosensitization for thoracic malignancy: a therapeutic approach on the basis of preclinical research of human cancer cell lines. Chen, Y., Pandya, K., Keng, PC., et al.[2015]

Combined chemotherapy with paclitaxel and carboplatin alongside thoracic radiation therapy has shown a clear survival benefit for patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), as demonstrated in randomized trials and meta-analyses.

Ongoing and planned multicenter studies aim to refine treatment regimens and improve both local and systemic control of NSCLC, highlighting the need for a multidisciplinary approach to effectively manage this systemic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. Belani, CP.[2015]

A combination treatment of paclitaxel, carboplatin, and oral etoposide was found to be highly effective and well tolerated in 117 patients with small-cell lung cancer, showing promising results in both extensive and limited stages of the disease.

The regimen can be safely administered alongside thoracic radiation therapy, with only a few patients experiencing esophagitis, indicating a favorable safety profile compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung cancer. Hainsworth, JD., Hopkins, LG., Thomas, M., et al.[2015]

In a phase I trial involving 10 patients with locally advanced non-small cell lung cancer, a combination of chemotherapy (paclitaxel and carboplatin) and thoracic irradiation showed a 57% response rate during the induction phase, indicating promising efficacy.

The study is assessing the maximum tolerated radiation dose, with initial results showing manageable toxicity; while some patients experienced grade 3 or 4 hematologic issues, no severe non-hematologic toxicities were reported, suggesting a favorable safety profile for the treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial. Socinski, MA., Clark, JA., Halle, J., et al.[2015]

In a phase II study involving 43 patients with locally advanced unresectable non-small cell lung cancer, the combination of weekly paclitaxel and carboplatin with hyperfractionated radiation therapy resulted in a high overall response rate of 78.6%, with 7.2% achieving a complete response.

The treatment was generally well-tolerated, although esophagitis was a significant side effect, affecting 26% of patients with grade 3 or 4 toxicity, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study). Choy, H., Devore, RF., Hande, KR., et al.[2019]

In a phase II study involving 23 previously untreated patients with stages IIIA or IIIB non-small cell lung cancer, the combination of paclitaxel, carboplatin, and concurrent radiation achieved a high overall response rate of 82%.

The treatment was associated with manageable toxicity, primarily esophagitis, affecting 45% of patients, but most recovered quickly, indicating that this regimen is a promising option for locally advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer. Choy, H., Akerley, W., Safran, H., et al.[2015]

In a phase 3 study involving 134 patients with locally advanced non-small cell lung cancer, low-dose pulsed paclitaxel combined with chemoradiotherapy significantly improved the tumor response rate (83.1% vs. 54.2%) compared to a higher weekly dose regimen.

Patients receiving the low-dose regimen also experienced better recurrence-free survival (14.6 months vs. 9.4 months) and had lower rates of severe hematologic toxicities, making it a safer option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Randomized Low-Dose Paclitaxel Chemoradiotherapy Study for Locally Advanced Non-Small Cell Lung Cancer. Lin, H., Chen, Y., Shi, A., et al.[2020]

In a phase II study involving 32 patients with locally advanced unresectable non-small cell lung cancer, the combination of weekly paclitaxel and carboplatin with hyperfractionated radiation therapy resulted in a high overall response rate of 77%, with 72.7% achieving a partial response.

The treatment was generally well-tolerated, although 35% of patients experienced severe esophagitis, indicating that while effective, the regimen does have notable side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary analysis of a phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small cell lung cancer. Choy, H., DeVore, RF., Hande, KR., et al.[2015]

Citations

1. foxchase.org foxchase.org/news/newer-radiation-technique-reduces-side-effects-while-maintaining-effectiveness

Newer Radiation Technique Reduces Side Effects While ... Researchers at Fox Chase Cancer Center have demonstrated that pulsed low dose rate (PLDR) chemoradiation therapy can significantly reduce ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4674173/

Local Tumor Control and Normal Tissue Toxicity of Pulsed ... Our experiments showed that the PLDR treatment was effective for the A549 tumors compared with conventional RT with standard dose rates, and the tumor growth ...

3. redjournal.org redjournal.org/article/S0360-3016(23)05690-0/fulltext

Impacts of Combining Pulsed Low Dose Rate ... PLDR combined with anti-PD-1 antibody can result in better tumor growth inhibition and significantly delay the survival time of mice.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03094884

NCT03094884 | Pulsed Low Dose Rate Radiation With ... Phase I study with the hypothesis that Pulsed Low Dose Radiation (PLDR) radiation delivery technique can significantly decrease the rate of severe acute ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35038688/

Pulsed low dose-rate radiotherapy: radiobiology and ... Preliminary results from early clinical studies have shown favorable outcomes for various treatment sites especially for recurrent cancers.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03094884

Pulsed Low Dose Rate Radiation With Concurrent ... Phase I study with the hypothesis that Pulsed Low Dose Radiation (PLDR) radiation delivery technique can significantly decrease the rate of severe acute ...

7. ascopost.com ascopost.com/news/october-2025/pulsed-low-dose-rate-chemoradiation-reduces-severe-esophagitis-in-esophageal-cancer-and-nsclc/

Pulsed Low-Dose–Rate Chemoradiation Reduces Severe ... Pulsed low-dose–rate radiation has been used to decrease toxicity, but there are no prospective data to date for safety of the technique in ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40575970/

Pulsed reduced dose rate radiotherapy: a narrative review Conclusions: PRDR radiotherapy shows promising efficacy and safety across various malignancies, especially in the re-irradiation setting. It is particularly ...

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

Pulsed reduced dose rate radiotherapy: a narrative review - Atak It is particularly effective for CNS tumors with manageable toxicity and shows potential in recurrent breast, head and neck, and gastrointestinal cancers.

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9007137/

Paclitaxel plus carboplatin and concurrent radiation ... Therapy with paclitaxel, carboplatin, and concurrent radiation is a promising treatment for patients with locally advanced non-small cell lung cancer.