High-Dose Radiation Therapy for Pancreatic Cancer

(ABLATE Trial)

Overseen By Anna Dodd

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Anti-cancer treatments

Disqualifiers: Metastatic disease, Age<18, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether high-dose radiation therapy can improve outcomes for individuals with locally advanced pancreatic cancer following chemotherapy. The main goal is to determine if this approach can slow cancer progression, enhance quality of life, or extend survival. Participants will receive radiation treatment, provide blood samples, and complete quality of life surveys. Those whose pancreatic cancer has remained stable or shrunk after chemotherapy may be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires a washout period of at least 2 weeks from your first-line chemotherapy before starting the study treatment. If you are currently on any anti-cancer treatment, including chemotherapy, you will need to stop those medications to participate in the trial.

What prior data suggests that high-dose radiation therapy is safe for pancreatic cancer patients?

Studies have shown that many patients with pancreatic cancer tolerate high-dose radiation therapy well. Research suggests that this treatment can improve survival rates when surgery cannot completely remove the cancer.

Some patients experience side effects, but these are often manageable. Common side effects include fatigue and nausea. However, not everyone experiences these, and medical teams closely monitor patients to manage any issues.

This trial is in Phase 2, indicating that some evidence already supports the treatment's safety, but researchers are still gathering more information. This phase helps confirm how well patients tolerate the treatment and its potential benefits. Consulting a healthcare professional about any concerns is always advisable to understand what to expect in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

High-dose radiation therapy is unique because it delivers a more concentrated dose of radiation directly to the pancreatic cancer cells, which could potentially improve the effectiveness of treatment with fewer sessions. Unlike standard radiation therapy, which typically involves lower doses over a longer period, this approach aims to minimize the exposure of healthy tissues to radiation, thereby reducing side effects. Researchers are excited because it could lead to quicker and more powerful results, offering new hope for patients with this challenging cancer.

What evidence suggests that high-dose radiation therapy might be an effective treatment for pancreatic cancer?

Research has shown that high-dose radiation therapy can effectively treat advanced pancreatic cancer. One study found that this method can relieve symptoms and extend the time patients live without cancer progression. Another study suggested that high doses of radiation might control cancer as effectively as surgery in some patients. New data indicate that increasing the radiation dose can better control the tumor and may improve survival rates. These findings offer hope that high-dose radiation therapy could enhance treatment outcomes for patients with advanced pancreatic cancer. ^{3 5 6 7 8}

Who Is on the Research Team?

Erica Tsang, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults with locally advanced pancreatic cancer smaller than 8 cm, who've had a positive response to initial chemotherapy. They must be fit enough for a biopsy, not pregnant or breastfeeding, have normal organ and marrow function, and an ECOG performance status ≤1. Life expectancy should be over 6 months.

Inclusion Criteria

My diagnosis of locally advanced pancreatic cancer was confirmed by tests.

My organs and bone marrow are functioning normally.

I am eligible for chemotherapy with FFX or GnP.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive standard of care induction chemotherapy to assess response

Varies

Radiation Therapy

Participants are treated with high dose radiation therapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• High Dose Radiation Therapy

Trial Overview The study tests high-dose radiation therapy's effectiveness on improving treatment outcomes and survival rates in patients whose pancreatic cancer has responded well to initial chemo. It includes optional biopsies, quality of life surveys, and blood sample donations for research.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

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 study of 68 pancreatic cancer patients undergoing hypofractionated radiotherapy, dosimetric parameters, particularly the absolute volume of the duodenum receiving radiation (aV45), were identified as significant predictors of gastrointestinal (GI) toxicity, with 18 patients experiencing grade II and 2 patients grade III toxicity.

To minimize the risk of GI toxicity during treatment, it is crucial to reduce the irradiated volume of the duodenum, as an aV45 of 0.5 cm³ was found to be the optimal threshold for predicting higher grades of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive dosimetric parameters for gastrointestinal toxicity with hypofractioned radiotherapy in pancreatic adenocarcinoma. Liu, X., Ren, G., Li, L., et al.[2020]

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 497 patients with locally advanced pancreatic cancer, those receiving a higher radiotherapy dose (≥61Gy) experienced significantly improved overall survival (OS), progression-free survival (PFS), and local failure-free rate (LFFR) compared to those receiving lower doses (<61Gy).

Importantly, the increased dose did not lead to higher rates of severe toxicity, suggesting that dose-escalated chemoradiotherapy can be a safe and effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy. Chung, SY., Chang, JS., Lee, BM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12511844/

Impact of Different Modalities of Radiotherapy in Locally ... Despite advances in oncological therapies, pancreatic cancer mortality has not substantially improved over the last decade, with a 5‐year mortality rate of 9%– ...

2. pfmjournal.org pfmjournal.org/journal/view.php?doi=10.23838/pfm.2024.00100

Redefining the role of radiation therapy in pancreatic ... Thus, RT can alleviate symptoms caused by gross tumor lesions, increase PFS, and improve long-term OS. However, to ensure the safety of the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1053429625000645

Review Article Intraoperative Radiation for Pancreatic Cancer Emerging data in PDAC suggest that improved local control and favorable survival can be achieved with radiation dose escalation. However, adjacent ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2777063

Association of Ablative Radiation Therapy With Survival ... This cohort study examines the use of hypofractionated ablative radiation therapy for patients with locally advanced pancreatic cancer ...

5. mskcc.org mskcc.org/news/high-dose-radiation-offers-hope-people-inoperable-pancreatic

High-Dose Radiation Offers Hope for People with ... A new MSK study suggests that in certain patients, high doses of radiation could control pancreatic cancer as well as surgery.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11795264/

Safety and efficacy of intraoperative radiation therapy using a ... Pancreatic cancer is associated with poor clinical outcomes and has a 5-year survival rate below 13%. Surgical resection remains the primary ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0167814025052144

Long-Term outcomes of ablative stereotactic body radiation ... Pancreatic cancer (PC) is one of the most lethal malignancies, with a 5-year survival rate of approximately 13 %[1]. Most patients present with ...

8. nrgoncology.org nrgoncology.org/GI011

NRG-GI011: Testing Higher Dose RT for Locally Advanced ... Researchers want to know if a higher dose of radiation is better, worse, or the same as the usual treatment for people with locally advanced pancreatic cancer.