Adaptive radiation therapy for locally advanced, unresectable pancreatic cancer.

Adaptive Radiation for Locally Advanced Unresectable Pancreatic Cancer: Phase I Dose Escalation Study

This trial will try adaptive radiation therapy to better target tumor cells and reduce side effects for people with locally advanced, unresectable pancreatic cancer.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fox Chase Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06984562 on ClinicalTrials.gov

What this trial studies

This single-center interventional study uses adaptive radiation therapy (ART) to personalize radiation delivery for patients with locally advanced, unresectable pancreatic ductal adenocarcinoma. Participants will undergo CT-based planning with possible placement of 1–3 small markers, a tumor biopsy, and serial blood draws, then receive five radiation treatments given every other day over two weeks. The protocol aims to adjust radiation targeting to concentrate dose on aggressive tumor areas while sparing surrounding healthy organs. Safety, feasibility, and preliminary signals of improved targeting and reduced toxicity will be recorded.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically or cytologically confirmed, locally advanced unresectable pancreatic ductal adenocarcinoma who have been reviewed by a multidisciplinary team and have received or are ineligible for induction chemotherapy.

Not a fit: Patients with metastatic disease, clearly resectable tumors, or those unable to undergo CT planning, marker placement, biopsy, or the prescribed radiation schedule are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, ART could improve tumor control while decreasing radiation damage to nearby organs, potentially reducing treatment-related side effects.

How similar studies have performed: Adaptive radiation has shown promise in other tumor sites, but its application specifically to locally advanced pancreatic cancer is relatively new and supported only by limited early data.

Eligibility criteria

Inclusion Criteria

1. Patients must have histologically or cytologically-confirmed PDA.
2. Patients must have locally advanced unresectable PDA.

   • This includes the following- per NCCN criteria\*: 2.1 Unreconstructible involvement with the superior mesenteric vein or portal vein due to tumor or bland thrombus OR 2.2 Solid tumor contact with greater than 180 degrees of the superior mesenteric artery or celiac artery OR 2.3. Solid tumor contact with the aorta OR 2.4. Patients with non-metastatic disease that is inoperable by virtue of the operation posing excessive risk to the patient

   \*All patients must have been reviewed in the multidisciplinary conference and determined to have unresectable disease by a pancreatic surgeon and to have received or be ineligible for induction chemotherapy based on medical oncology assessment. Documentation of this review in EPIC meeting minutes will satisfy this requirement.
3. Patients enrolled onto the dose escalation arm may have started chemotherapy prior to initiation of radiation therapy and the last dose of chemotherapy must occur at least 2 weeks before start of ART.
4. Eastern Cooperative Oncology Group, or ECOG, performance status 0-2.
5. Adequate bone marrow, hepatic, renal function:

   * ANC ≥ 1,500/µl and PLT ≥ 100,000/µl
   * Bilirubin less than 1.5 ULN
   * AST and ALT \< 3X ULN
   * Serum Creatinine \<1.5X ULN
6. Women of childbearing potential must not be pregnant (negative pregnancy test within 72 hours prior to registration). Postmenopausal woman must have been amenorrheal and non-lactating for at least 12 months to be considered of non-childbearing potential. Men and women of childbearing potential must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for at least 6 months after therapy is completed.
7. Age ≥ 18 years
8. Participants must sign a written informed consent and HIPAA consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment, tissue sample collections, and follow-up.

Exclusion Criteria

1. Radiologically or cytologically confirmed metastatic disease.
2. Patients who have had any prior radiation therapy for pancreatic cancer.
3. Patients who have had prior chemoradiation to an overlapping volume.
4. Patients with adenosquamous carcinoma of the pancreas.
5. Subjects who have had chemotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier to \< Grade 2. Patients who received previous immunotherapy or other antibody therapy, within 28 days (immune related toxicities must have resolved to \<= Grade 2 prior to starting treatment). Study treatment may be started within these washout periods or with continuing toxicities if considered by the Sponsor-Investigator to be safe and within the best interest of the patient.
6. Concurrent non-study chemotherapy or biologic therapy.
7. A history of ataxia telangiectasia or other documented history of radiation hypersensitivity.

   • Includes both bi- and mono-allelic likely pathogenic or pathogenic ATM mutations (VUS is acceptable).
8. Serious, active infections requiring treatment with IV antibiotics

Where this trial is running

Philadelphia, Pennsylvania

• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Joshua Meyer, MD — Fox Chase Cancer Center
• Study coordinator: Joshua Meyer, MD

Conditions Locally Advanced Pancreatic Ductal Adenocarcinoma; Adaptive Radiation Therapy; Pancreatic Ductal Adenocarcinoma; Locally advanced unresectable PDA