High-Dose Radiation + Chemotherapy for Pancreatic Cancer

(MAIBE Trial)

Recruiting at 9 trial locations

Overseen By Christopher Crane, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: FOLFIRINOX, Gemcitabine, Nab-paclitaxel

Disqualifiers: Pregnancy, Heart failure, Angina, 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

47 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 2 weeks or 5 half-lives for any investigational (experimental) agents before starting radiation therapy. For other medications, the protocol does not specify if you need to stop taking them.

What data supports the effectiveness of the treatment High-Dose Radiation + Chemotherapy for Pancreatic Cancer?

Research shows that combining high-dose radiation with chemotherapy, like 5-FU or capecitabine, improves survival rates in pancreatic cancer patients compared to radiation alone. In one study, 40% of patients receiving combined treatment were alive after one year, compared to only 10% with radiation alone. ^{1 2 3 4 5}

Is the combination of high-dose radiation and chemotherapy safe for pancreatic cancer patients?

Studies have shown that using high-dose radiation (IMRT) with chemotherapy drugs like capecitabine is generally safe for patients with pancreatic cancer, though it can have side effects. Researchers have tested these treatments to find the safest doses and monitor any toxic effects. ^{2 4 5 6 7}

How is the treatment of high-dose radiation and capecitabine unique for pancreatic cancer?

This treatment combines high-dose radiation with capecitabine (a chemotherapy drug) using a method called hypofractionated ablative IMRT, which allows for higher doses of radiation to be delivered more precisely to the tumor while minimizing damage to surrounding healthy tissue. This approach is unique because it aims to improve local control of the cancer by overcoming the limitations of traditional radiation therapy. ^{2 5 6 7 8}

What is the purpose of this trial?

This study is being done to test whether receiving a dose of radiation that is higher than the standard dose, in combination with chemotherapy, improves the chance of becoming a candidate for surgery and improves the chance of extending the patient's life.

Research Team

Marsha Reyngold, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with advanced pancreatic cancer who've completed at least 3 months of standard chemotherapy without distant metastasis. They must have good organ function, no prior abdominal radiotherapy, and not be pregnant or breastfeeding. Men and women must agree to use contraception.

Inclusion Criteria

Your platelet count is higher than 75,000 per microliter.

My cancer is a type of pancreatic cancer confirmed by a biopsy.

My cancer has not spread to distant parts of my body after initial chemotherapy.

Exclusion Criteria

I cannot undergo surgery due to other health issues.

My cancer is at a stage where surgery might be possible.

I do not have any uncontrolled illnesses like infections or heart problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive HFA-IMRT to a total dose of 67.5 Gy in 15 fractions or 75 Gy in 25 fractions with concurrent capecitabine

3-5 weeks

Assessment

Cross-sectional imaging is repeated to assess for resectability

4-6 weeks after the end of CRT

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Capecitabine
• Hypofractionated ablative IMRT (HFA-IMRT)

Trial Overview The study tests if high-dose radiation therapy combined with capecitabine (a chemotherapy drug) can make patients eligible for surgery and extend their lives compared to the standard treatment.

Participant Groups

Group I: HFA-IMRT Experimental Treatment 2 Interventions

Eligible patients will receive HFA-IMRT to a total dose of 67.5 Gy in 15 fractions or 75Gy in 25 fractions to areas of gross tumor with concurrent capecitabine. Cross-sectional imaging will be repeated 4-6 weeks after the end of CRT to assess for resectability.

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

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In a pilot study involving 10 patients with unresectable pancreatic adenocarcinoma, hypofractionated intensity modulated radiotherapy (H-IMRT) demonstrated a high local control rate, with tumor response observed in 9 out of 10 patients.

The treatment was associated with manageable gastrointestinal toxicity, which correlated with the dose received by the duodenum, and resulted in promising 1-year overall and disease-free survival rates of 83.3% and 68.6%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated intensity-modulated radiotherapy in locally advanced unresectable pancreatic cancer: A pilot study. De Felice, F., Benevento, I., Bulzonetti, N., et al.[2020]

In a study involving 15 patients with locally advanced pancreatic cancer, capecitabine combined with radiotherapy was found to be feasible, with a recommended dose of 800 mg/m2 bid for further evaluation.

While some patients experienced side effects like grade 3 diarrhea, the treatment showed potential efficacy with 20% achieving a partial response, suggesting that capecitabine could serve as a simpler alternative to intravenous fluorouracil for enhancing the effects of radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: expression analysis of genes related to outcome. Saif, MW., Eloubeidi, MA., Russo, S., et al.[2015]

In a phase I study involving 25 patients with localized, inoperable pancreatic adenocarcinoma, capecitabine was found to be well tolerated when given concurrently with radiotherapy, with a recommended dose of 825 mg/m².

The study identified only mild dose-limiting toxicities, such as grade 3 vomiting and fatigue, and no significant hematological toxicities, indicating a favorable safety profile for this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer. Roxburgh, P., Lumsden, GR., Paul, J., et al.[2022]

In a study involving 9 patients with locally advanced pancreatic cancer, hypofractionated radiotherapy at 45 Gy in 15 fractions was well-tolerated, with no dose-limiting toxicities observed, allowing for timely initiation of full-dose gemcitabine chemotherapy.

However, the lower dose of 40 Gy in 8 fractions resulted in significant side effects, preventing timely chemotherapy initiation in most patients, indicating that this regimen is not feasible for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of hypofractionated radiotherapy followed by systemic chemotherapy with full-dose gemcitabine in patients with unresectable locally advanced pancreatic cancer. Furuse, J., Ishii, H., Kawashima, M., et al.[2022]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Dose escalation of concurrent hypofractionated radiotherapy and continuous infusion 5-FU-chemotherapy in advanced adenocarcinoma of the pancreas. [2018]

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

Intensity-modulated radiotherapy (IMRT) and concurrent capecitabine for pancreatic cancer. [2022]

3. 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]

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

Induction Chemotherapy Followed by Concurrent Full-dose Gemcitabine and Intensity-modulated Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma. [2022]

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

Hypofractionated intensity-modulated radiotherapy in locally advanced unresectable pancreatic cancer: A pilot study. [2020]

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

Phase I study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: expression analysis of genes related to outcome. [2015]

7. Germany pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

A phase I study of hypofractionated radiotherapy followed by systemic chemotherapy with full-dose gemcitabine in patients with unresectable locally advanced pancreatic cancer. [2022]