PLDR Radiation for Pancreatic Cancer

Overseen By Meghann Hainsworth

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Fox Chase Cancer Center

Must be taking: Gemcitabine

Must not be taking: Non-study chemotherapy

Disqualifiers: Metastatic disease, Radiation hypersensitivity, Scleroderma, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new radiation treatment called pulsed low-dose rate (PLDR) radiation for pancreatic cancer patients. The researchers aim to determine if combining this radiation with the chemotherapy drug gemcitabine can treat pancreatic adenocarcinoma without damaging surrounding healthy tissue. It targets individuals with non-metastatic pancreatic cancer not yet ready for surgery, particularly if the cancer affects certain blood vessels or if immediate surgery is not feasible. Participants must have a diagnosis of pancreatic adenocarcinoma and a treatment plan that includes surgery following chemoradiation. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could potentially improve outcomes for future 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 if you have had chemotherapy before joining, you must have a 2-week period without it before starting the trial.

What prior data suggests that PLDR radiation is safe for pancreatic cancer treatment?

Research has shown that pulsed low-dose rate (PLDR) radiation reduces harm to healthy tissues by dividing the dose into smaller parts, allowing healthy cells time to heal. This method protects non-cancerous cells, making it a safer choice compared to standard radiation methods.

The chemotherapy drug gemcitabine is already used to treat pancreatic cancer, with its safety well-documented and side effects manageable when administered carefully. Combining PLDR radiation with gemcitabine aims to provide a more tolerable treatment for patients by minimizing damage to healthy tissues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for pancreatic cancer involve high-dose radiation, which can cause significant side effects. But PLDR (pulse-low-dose rate) radiation is unique because it delivers radiation in small, frequent doses, potentially reducing damage to healthy cells. This method is paired with gemcitabine chemotherapy, aiming to enhance treatment effectiveness while minimizing harm. Researchers are excited about PLDR because it could offer a gentler yet effective approach for patients, potentially leading to better quality of life during treatment.

What evidence suggests that PLDR radiation might be an effective treatment for pancreatic cancer?

Research has shown that a new type of radiation treatment, called pulsed low-dose-rate (PLDR) radiation, might be more effective and safer for treating pancreatic cancer than standard radiation. PLDR radiation delivers treatment in small bursts, allowing healthy cells to recover better while still targeting cancer cells. This method has improved outcomes for cancers in the abdomen and pelvis. Another study found that PLDR makes the area around the tumor less supportive of cancer growth. In this trial, participants will receive PLDR radiation combined with the chemotherapy drug gemcitabine, which could offer a promising treatment for pancreatic cancer. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with non-metastatic pancreatic cancer not ready for immediate surgery. They may have had prior chemo, but must have a washout period before joining. Participants need to be able to perform daily activities (ECOG status 0-2) and agree to use birth control. Excluded are those with previous radiation therapy for pancreatic cancer, uncontrolled illnesses, or certain conditions like scleroderma.

Inclusion Criteria

You are not physically able to have a major surgery right now.

Patients must have non-metastatic pancreatic cancer not appropriate for immediate surgical resection, as judged by the operating surgeon in conjunction with a radiologist prior to enrollment.

You need to have a way for the doctors to measure your disease using specific criteria.

Exclusion Criteria

Concurrent non-study chemotherapy or biologic therapy.

You have not received any treatment for pancreatic cancer, except for chemotherapy.

Uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements.

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-rate (PLDR) radiation and weekly gemcitabine chemotherapy

6-7 weeks

Weekly visits for radiation and chemotherapy

Surgery

Standard surgery to remove the cancer after consultation with a surgeon

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PLDR

Trial Overview

The study tests PLDR radiation combined with the chemotherapy drug gemcitabine in patients with pancreatic adenocarcinoma who can't immediately undergo surgery. The goal is to see if this new type of radiation causes less damage to healthy tissue compared to standard treatments.

How Is the Trial Designed?

Group I: PLDR Chemoradiation Experimental Treatment 1 Intervention

Patients will receive pulse-low-dose rate radiation, along with gemcitabine chemotherapy. 6 patients each will be accrued at two dose levels. PLDR radiation will be delivered as 10 fractions of 20 cGy, initiated once every 3 minutes. Dose levels will be selected as follows: Dose level 1: 56 Gy; Dose level 2: 66 Gy

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

Recent data indicate that pancreatic adenocarcinoma may not be as resistant to radiation as previously thought, suggesting that it could potentially be curable in some cases, which supports the use of pancreatic biopsy even when the disease is deemed unresectable.

Effective treatment with radiation for pancreatic cancer is dose-dependent, and advancements in precision treatment planning and delivery methods, such as interstitial implantation and intraoperative electron beam therapy, are being explored to enhance outcomes while minimizing damage to surrounding healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current radiotherapeutic approaches to pancreatic cancer. Dobelbower, RR.[2019]

Intraoperative radiation therapy (IORT) with electrons was administered to 52 patients with locally advanced pancreatic cancer, showing acceptable acute and chronic tolerance to the treatment.

Local progression of cancer was infrequent (7% in evaluable patients), but there was no significant improvement in median or long-term survival, likely due to the high rates of liver and peritoneal metastases associated with pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative and external beam irradiation +/- 5-FU for locally advanced pancreatic cancer. Gunderson, LL., Martin, JK., Kvols, LK., et al.[2019]

In a phase I trial involving 37 patients with advanced pancreatic cancer, the maximum-tolerated radiation dose concurrent with full-dose gemcitabine was determined to be 36 Gy, as higher doses (42 Gy) resulted in significant acute and late gastrointestinal toxicities.

The study suggests that while the highest radiation dose tested was not safe, the lower dose of 36 Gy is recommended for further investigation in a phase II trial due to better tolerance and promising survival data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. McGinn, CJ., Zalupski, MM., Shureiqi, I., et al.[2022]

In a study of 200 patients with locally advanced pancreatic cancer, those receiving dose-escalated intensity modulated radiation therapy (IMRT) with a biologically effective dose (BED) greater than 70 Gy showed significantly improved overall survival (OS) of 17.8 months compared to 15.0 months for those with lower doses.

The higher radiation dose also led to better local-regional recurrence-free survival (RFS) of 10.2 months versus 6.2 months, without increasing toxicity, indicating that dose escalation can be a safe and effective strategy in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation. Krishnan, S., Chadha, AS., Suh, Y., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04452357

Pulse-low-dose Rate (PLDR) Radiation in Pancreatic Cancer

Pulsed low-dose-rate (PLDR) radiation improves the safety of radiation through breaking it up into small pulses. This increases the repair of DNA damage in ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8435343/

Pulsed low-dose rate radiotherapy has an improved ...

Pulsed low-dose rate radiotherapy has an improved therapeutic effect on abdominal and pelvic malignancies.

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38293200/

Pulsed low-dose-rate radiation (PLDR) reduces the tumor ...

Our findings support the ongoing NCT04452357 clinical trial testing PLDR safety and TME normalization potential in pancreatic cancer patients.

4.

aacrjournals.org

aacrjournals.org/clincancerres/article/27/8_Supplement/PR-006/672034/Abstract-PR-006-Pulsed-low-dose-rate-radiation

Abstract PR-006: Pulsed low-dose-rate radiation (PLDR) limits ...

Pulsed low-dose-rate (PLDR) radiation improves the safety of radiation treatment as it allows time for DNA damage repair in non-tumorous cells/ ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.682

Pulsed low dose rate radiation to mitigate tumor-permissive ...

PLDR mitigates conventional CRT-based TNT-induced tumor-permissive responses, restoring the fibroblastic units' tumor-suppressive function.

6.

cco.amegroups.org

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

Pulsed reduced dose rate radiotherapy: a narrative review - Atak

Conclusions: PRDR radiotherapy shows promising efficacy and safety across various malignancies, especially in the re-irradiation setting. It is particularly ...

7.

withpower.com

withpower.com/trial/phase-pancreatic-neoplasms-2020-74a9b

PLDR Radiation for Pancreatic Cancer · Info for Participants

PLDR radiation therapy has been shown to reduce the risk of damage to normal tissues compared to other radiation techniques, which suggests it is generally safe ...