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

Trial Summary

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 data supports the effectiveness of high-dose radiation therapy for pancreatic cancer?

Research shows that combining high-dose radiation with the drug 5-fluorouracil (5-FU) significantly improves survival rates for patients with pancreatic cancer compared to radiation alone. Additionally, high-dose radiation therapy can help control local tumor growth and provide pain relief in some patients. ^{1 2 3 4 5}

Is high-dose radiation therapy generally safe for humans?

High-dose radiation therapy for pancreatic cancer has been studied, and while it can cause gastrointestinal side effects like nausea and digestive issues, these are often mild to moderate. Some patients may experience more severe side effects, but these are less common. ^{6 7 8 9 10}

How does high-dose radiation therapy differ from other treatments for pancreatic cancer?

High-dose radiation therapy for pancreatic cancer is unique because it involves delivering very high doses of radiation directly to the tumor, which requires precise targeting to avoid damaging nearby healthy tissues. This approach can be combined with other treatments like chemotherapy to improve local tumor control, although it does not significantly improve overall survival due to the high rate of distant metastases. ^{3 5 8 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to test the effect of high-dose radiation therapy after initial chemotherapy in patients with locally advanced pancreatic cancer. The main question it aims to answer is: • For patients with locally advanced pancreatic cancer that responded to initial chemotherapy (stayed stable or decreased in size), will high-dose RT (radiation therapy) contribute to improving treatment outcomes, enhancing quality of life, or increasing overall survival rates? Participants will: * Undergo an optional tumor biopsy. * Be treated with high dose radiation therapy. * Complete quality of life questionnaires. * Donate research blood samples.

Research Team

Erica Tsang, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

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

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

Treatment Details

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+

Findings from Research

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]

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 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]

References

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

Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Change of 5-fluorouracil penetration in blood-pancreatic barrier of rats after high-dose radiotherapy]. [2013]

3. France pubmed.ncbi.nlm.nih.gov

[Role and results of radiotherapy in the treatment of pancreatic adenocarcinoma]. [2009]

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

The role of intraoperative radiation therapy in patients with pancreatic cancer. [2014]

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

Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations. [2016]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Predictive dosimetric parameters for gastrointestinal toxicity with hypofractioned radiotherapy in pancreatic adenocarcinoma. [2020]

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

Pancreatic Cancer: Feasibility and Outcome After Radiochemotherapy with High Dose External Radiotherapy for Non-resected and R1 Resected Patients. [2022]

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

Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. [2022]

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

Intraoperative and external beam irradiation +/- 5-FU for locally advanced pancreatic cancer. [2019]

10. Ireland pubmed.ncbi.nlm.nih.gov

Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Combined isodose curves of high-dose rate interstitial brachytherapy with external-beam radiation therapy in pancreatic carcinoma. [2016]

12. Germany pubmed.ncbi.nlm.nih.gov

[Intraoperative and percutaneous radiotherapy of pancreatic carcinoma]. [2019]