Radiation for Pancreatic Cancer

Overseen By Ethan Ludmir, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Metastatic effusion, Leptomeningeal disease, Peritoneal carcinomatosis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding targeted radiation (Metastasis-Directed Therapy) to standard treatment benefits people with a specific type of pancreatic cancer that has spread to a few other areas. The main goal is to determine if this approach can extend the time patients live without disease progression and improve overall survival. Suitable candidates for this trial have pancreatic ductal adenocarcinoma that has spread to one to five other locations and can receive radiation or other local treatments for all visible cancer. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to access potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that radiation therapy, like the kind studied in this trial, is generally well-tolerated by patients with pancreatic cancer. Studies have found that this treatment can help manage the disease by directly targeting cancer cells.

Patients who previously received radiation therapy reported few serious side effects. For instance, one study found that most patients did not experience severe stomach or digestive problems after treatment. This finding is encouraging as it suggests the treatment is manageable for many people.

Additionally, radiation therapy is commonly used to control tumor growth in various cancers and is often part of standard care. Doctors have extensive experience using it safely. While some side effects may occur, they are usually mild and manageable with assistance from the healthcare team.

Overall, evidence suggests that radiation therapy is a safe option for many people. It can play an important role in improving quality of life by helping to control cancer growth. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about consolidative radiation for pancreatic cancer because it offers a new approach by directly targeting metastatic sites with precise radiation, known as Metastasis-Directed Therapy (MDT). Unlike standard treatments like chemotherapy, which affect the entire body, MDT focuses on specific areas where cancer has spread, potentially reducing side effects and improving the patient's quality of life. Additionally, MDT might enhance the effectiveness of systemic therapies by controlling tumor growth more effectively, offering hope for better outcomes in a cancer type that's notoriously difficult to treat.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that adding targeted radiation therapy to chemotherapy for pancreatic cancer can greatly improve patient outcomes. Specifically, studies have found that this combination can increase the time patients live without the cancer worsening by more than four times. This trial will compare two approaches: one group will receive Metastasis-Directed Therapy (MDT), which includes consolidative radiation, while the other group will receive systemic therapy alone. Radiation therapy helps control the local spread of cancer, but its effect on overall survival varies. Overall, these findings suggest that radiation therapy could be a promising option for those with pancreatic cancer, especially in extending the time without disease progression. ^{6 7 8 9 10}

Who Is on the Research Team?

Ethan Ludmir, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

The EXPAND trial is for individuals with a specific type of pancreatic cancer (PDAC) that has spread to a limited number of other areas in the body. Details on who can join are not fully provided, but typically participants would need to meet certain health standards and have oligometastatic disease.

Inclusion Criteria

I am a man who can father children and will use birth control.

My scans show a few cancer spread spots, as per RECIST criteria.

I can perform all self-care but may not be able to do heavy physical work.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

I have another cancer that significantly threatens my life.

Known psychiatric or substance abuse disorder/s interfering with trial participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Metastasis-Directed Therapy (MDT) or systemic therapy alone

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Consolidative Radiation

Trial Overview This study tests whether using Consolidative Radiation improves survival times for patients with PDAC and limited metastasis. It's a phase III trial, meaning it's one of the final steps before potential approval for widespread use if successful.

How Is the Trial Designed?

Group I: System Therapy (control) Experimental Treatment 1 Intervention

Patients will be randomized 1:1 to (a) MDT or (b) systemic therapy alone (no MDT).

Group II: MDT (Metastasis-Directed Therapy) Experimental Treatment 1 Intervention

Patients will be randomized 1:1 to (a) MDT or (b) systemic therapy alone (no MDT).

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 14 patients who underwent surgery for pancreatic cancer, high-dose chemoradiation combined with 5-fluorouracil (5-FU) was well tolerated, with no patients requiring treatment breaks and only limited grade 3 acute toxicity observed.

The approach showed a 3-year survival rate of 21%, suggesting that dose escalation of postoperative therapy is feasible and safe, warranting further investigation in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of dose escalation using concurrent radiation and 5-fluorouracil therapy following pancreaticoduodenectomy for pancreatic carcinoma. Regine, WF., John, WJ., McGrath, P., et al.[2019]

Chemoradiation may improve survival in localized pancreatic cancer, but recent trials suggest that chemotherapy alone might be more effective, especially due to challenges in patient selection and staging.

A combined treatment strategy of initial chemotherapy followed by chemoradiation is proposed to maximize patient outcomes, with ongoing research into new radiation techniques and neoadjuvant approaches for better targeting of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The integration of chemoradiation in the care of patient with localized pancreatic cancer. Crane, CH., Varadhachary, G., Settle, SH., et al.[2023]

In a pilot study involving 12 patients with non-resectable pancreatic adenocarcinomas, the combination of chemotherapy and radiotherapy showed a 25% response rate, with some patients experiencing complete responses lasting up to 16 months.

While the treatment demonstrated some efficacy, it also resulted in significant toxicity, including digestive issues and severe blood cell reductions, leading researchers to suggest exploring less toxic treatment combinations before larger randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination radiotherapy and chemotherapy in the treatment of locally advanced adenocarcinoma of the pancreas. Experiences of the Gustave Roussy Institute]. Eschwege, F., Rougier, P., Delanian, S., et al.[2013]

Intensity-modulated radiation therapy (IMRT) significantly reduces treatment-related toxicities such as nausea, vomiting, diarrhea, and late gastrointestinal issues in pancreatic cancer patients compared to traditional 3D-conformal radiation therapy (3D-CRT).

Despite the reduction in toxicities with IMRT, there was no significant difference in overall treatment outcomes between IMRT and 3D-CRT, suggesting that while IMRT may be safer, it does not necessarily improve effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of toxicity after IMRT and 3D-conformal radiotherapy for patients with pancreatic cancer - a systematic review. Bittner, MI., Grosu, AL., Brunner, TB.[2022]

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]

In a study of 22 patients with locally advanced pancreatic cancer (LAPC) who received radiotherapy after chemotherapy, advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) showed improved progression-free survival (PFS) compared to conventional radiotherapy, with median PFS of 7.1 months versus 2.6 months (P = 0.029).

No severe toxicities (grade III or IV) were reported, indicating that these modern radiotherapy techniques are not only effective but also safe for patients, particularly those who had prolonged chemotherapy before radiation, which correlated with better overall survival (19.0 months vs. 8.5 months for PRCT < 9 months, P = 0.049).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated and image-guided radiotherapy in patients with locally advanced inoperable pancreatic cancer after preradiation chemotherapy. Sinn, M., Ganeshan, R., Graf, R., et al.[2018]

Neoadjuvant chemoradiation for locally advanced pancreatic cancer can lead to secondary resectability in many patients, significantly improving their overall prognosis, making it a valuable option in treatment planning.

Modern radiation techniques, such as intensity-modulated and stereotactic body radiation therapy, enhance treatment effectiveness while reducing toxicity, highlighting the importance of ongoing research into optimal treatment strategies and patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant radiotherapeutic strategies in pancreatic cancer. Roeder, F.[2022]

In a study of 33 patients with pancreatic tumors, optimizing patient positioning (supine vs. prone) during radiation therapy significantly reduced the radiation dose to critical organs like the duodenum and stomach while maintaining the prescribed dose to the tumor.

By carefully selecting patient positioning for each beam angle, the study achieved reductions in radiation exposure to the duodenum and stomach by up to 6.4Gy and improved the dose coverage of the tumor and planning target volume by up to 6.9%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of patient positioning on carbon-ion therapy planned dose distribution to pancreatic tumors and organs at risk. Miki, K., Fukahori, M., Kumagai, M., et al.[2017]

In a study of 44 patients with unresectable pancreatic tumors receiving stereotactic body radiotherapy (SBRT), it was found that keeping the duodenal dose below 31.4Gy can maintain a 10% risk threshold for severe complications, such as hemorrhage or stricture.

The research established that a D1cc (the maximum dose to 1 cubic centimeter of tissue) of 25.3Gy is associated with a low risk (4.7%) of serious duodenal complications, while a higher dose of 37.4Gy significantly increases the risk to 20%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Volume Histogram Analysis of Stereotactic Body Radiotherapy Treatment of Pancreatic Cancer: A Focus on Duodenal Dose Constraints. Goldsmith, C., Price, P., Cross, T., et al.[2018]

Radiotherapy is not typically used before surgery for resectable pancreatic tumors but can be beneficial after surgery, especially if there are close or positive margins, to improve outcomes.

For borderline resectable tumors, pre-operative radiation has been shown to enhance surgical outcomes by reducing the rates of positive margins and nodal positivity, indicating its potential role in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for Pancreatic Adenocarcinoma: Recent Developments and Advances on the Horizon. Salamekh, S., Gottumukkala, S., Park, C., et al.[2023]

In a study involving 13 patients with unresectable pancreatic cancer, both double scattering (DS) and pencil beam scanning (PBS) proton therapy were found to significantly reduce low-dose radiation exposure to critical organs like the stomach and duodenum compared to intensity-modulated radiation therapy (IMRT).

However, proton therapy did not decrease the high-dose radiation exposure to these organs, indicating that while it may help limit low to intermediate doses, its overall impact on high-dose regions needs further investigation to assess clinical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas. Thompson, RF., Mayekar, SU., Zhai, H., et al.[2022]

Pancreatic adenocarcinoma (PAC) has poor clinical outcomes, with high rates of local recurrences and low overall survival compared to other solid tumors, indicating a need for improved treatment strategies.

The role of radiation therapy in treating PAC is under scrutiny due to conflicting results from clinical trials, highlighting the necessity for modern techniques and novel therapies to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy for pancreatic adenocarcinoma, a treatment option that must be considered in the management of a devastating malignancy. Hall, WA., Goodman, KA.[2020]

Surgery is the primary treatment for pancreatic cancer, but it rarely leads to long-term cures, emphasizing the need for additional therapies like radiation.

Recent advancements in radiation therapy techniques have improved the ability to deliver higher doses while reducing side effects, which may enhance treatment outcomes for patients with unresectable pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curative radiation therapy for pancreatic malignancies. Cooke, EW., Hazard, L.[2022]

Citations

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Survival benefit of local consolidative therapy for patients ... Notably, 31 patients who underwent surgery in combination with radiotherapy had the best survival outcomes than those who received surgery or ...

2. healio.com healio.com/news/hematology-oncology/20240823/metastasisdirected-radiation-therapy-may-be-paradigm-shift-in-advanced-pancreatic-cancer

Metastasis-directed radiation therapy may be 'paradigm ... Researchers observed a more than fourfold improvement in PFS with the addition of metastasis-directed therapy to chemotherapy.

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radiation therapy boosts progression-free survival in ... Approach achieves some of the longest progression-free survival times reported in a clinical trial for metastatic pancreatic cancer.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625001622

A Critical Review of Radiation Therapy for Locally ... Randomized trials have demonstrated a local control (LC) benefit of adding RT to chemotherapy but did not demonstrate an OS benefit.5,6 While RT can offer ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12468599/

Radiotherapy for Locally Advanced Pancreatic Cancer in ... The median OS rates at 1-, 2-, and 3-year were 71% (range: 24–95%), 29% (0–71%), and 13% (0–49%), respectively. According to RT techniques, the ...

7. 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 ...

8. dmr.amegroups.org dmr.amegroups.org/article/view/8812/html

The role of radiotherapy in metastatic pancreatic cancer Radiation therapy can play an important role in palliation of local tumor invasion, with the potential for benefit as metastasis-directed therapy.

9. 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 ...

10. thegreenjournal.com thegreenjournal.com/article/S0167-8140(23)09371-4/fulltext

Stereotactic MR-guided on-table adaptive radiation therapy ... Long-term outcomes include 2-year overall survival from diagnosis and SMART of 53.6 % and 40.5 %, respectively, and minimal late grade ≥ 3 GI ...