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This phase Ib/II study is a prospective, open-label, single arm, nonrandomized study of PEP503(radio-enhancer).
There are 2 portions in this study.
The target population is composed by patients who have confirmed adenocarcinoma of the rectum which is T3-4, N any, or locally unresectable, with tumor distal margin within 10 cm of the anal verge, with no evidence of distant metastatic disease, ECOG performance 0-1, and adequate bone marrow, renal and hepatic function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PEP503+5-FU/capecitabine+Radiotherapy | Experimental | Patients will receive PEP503 given as intratumor injection on Day 1, followed by preoperative radiation therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PEP503 | Drug | The volume of PEP503 to be administered is based on the baseline tumor volume of each patient. There will be 4 dose levels in Phase Ib. |
|
| Measure | Description | Time Frame |
|---|---|---|
| safety profile /the Dose Limiting Toxicity (DLT) | Safety as assess the safety profile and determine the Dose Limiting Toxicity (DLT) of PEP503 given as intratumor injection and activated by external beam radiation, with concurrent chemotherapy in patients with unresectable rectal cancer | up to 36 months |
| the recommended volume (dose) | recommended volume (dose) of PEP503 examined by given as intratumor injection and activated by external beam radiation. with concurrent chemotherapy in patients with unresectable rectal cancer | up to 36 months |
| anti-tumor activity | Anti-tumor activity as assessed by response rate (RR, as per RECIST 1.1) of PEP503 at the recommended volume given as intratumor injection and activated by external beam radiation, with concurrent chemotherapy in patients with unresectable rectal cancer | up to 36 months |
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Inclusion Criteria
Histologically proven adenocarcinoma of the rectum which is T3-4, N any, or locally unresectable disease , without evidence of distant metastases (M0)
Distant border of the tumor must be located ≤ 10 cm from the anal verge
Staging with MRI, transrectal ultrasound or CT-scan to confirm stage and resectability
ECOG performance 0 - 1
Age: 20 - 80 years old
Adequate bone marrow, renal, and hepatic function as:
All female patients of childbearing potential must have negative urine pregnancy test within the 7 days prior study treatment with PEP503. Patients must agree to use effective contraception during the study
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jwa-Yuan Wang, phD | Kaohsiung Municipal United Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kaohsiung Medical University Hospital | Kaohsiung City | Taiwan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 2425199 | Background | Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986 Jun 28;1(8496):1479-82. doi: 10.1016/s0140-6736(86)91510-2. | |
| 11684209 | Background | Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet. 2001 Oct 20;358(9290):1291-304. doi: 10.1016/S0140-6736(01)06409-1. |
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| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
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| ID | Term |
|---|---|
| D005472 | Fluorouracil |
| D000069287 | Capecitabine |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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|
| 5-fluorouracil | Drug | 225 mg/m2 a day, 5 days/week for 5 weeks during radiotherapy period |
|
|
| capecitabine | Drug | 825 mg/m2 BID 5 days/week for 5 weeks during the radiotherapy period |
|
|
| surgical resection | Procedure | Approximately 8 weeks after the completion of chemoradiotherapy, surgical resection of the tumor (total mesorectal excision, TME) will be performed once the tumor become resectable. |
|
| Radiotherapy | Radiation | Intensity-modulated radiation therapy (IMRT) or intensity modulated arc therapy (IMAT) of 5,000 cGy in 25 fractions (200 cGy/fraction, 5 times/week) to gross tumor and involved nodes and 4,500 cGy in 25 fractions (180 cGy/fraction, 5 times/week) to pelvis, starting at 24 hours after PEP503 injection. |
|
| 25732387 | Background | Lubowski DZ. Rectal cancer: the evolving role of adjuvant radiotherapy. ANZ J Surg. 2015 Mar;85(3):99-100. doi: 10.1111/ans.12916. No abstract available. |
| 24218281 | Background | Tural D, Selcukbiricik F, Yildiz O, Elcin O, Erdamar S, Guney S, Demireli F, Buyukunal E, Serdengecti S. Preoperative versus postoperative chemoradiotherapy in stage T3, N0 rectal cancer. Int J Clin Oncol. 2014 Oct;19(5):889-96. doi: 10.1007/s10147-013-0636-4. Epub 2013 Nov 12. |
| 19525947 | Result | Nel AE, Madler L, Velegol D, Xia T, Hoek EM, Somasundaran P, Klaessig F, Castranova V, Thompson M. Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater. 2009 Jul;8(7):543-57. doi: 10.1038/nmat2442. Epub 2009 Jun 14. |
| 40255171 | Derived | Huang CW, Hu HM, Hsu WH, Chen CY, Huang MY, Chen CP, Wei PL, Shen BN, Chang TK, Wang JY. Results of phase Ib/II trial of PEP503 (NBTXR3, radioenhancer) with chemoradiotherapy in patients with rectal cancer. Nanomedicine (Lond). 2025 May;20(9):929-941. doi: 10.1080/17435889.2025.2487411. Epub 2025 Apr 21. |
| 37166053 | Derived | Huang CW, Hu HM, Hsu WH, Chen CY, Huang MY, Chen CP, Wei PL, Shen BN, Wang JY. A phase Ib/II trial of PEP503 (NBTXR3, radioenhancer) with radiotherapy and chemotherapy in patients with rectal cancer. Nanomedicine (Lond). 2023 Mar;18(6):511-524. doi: 10.2217/nnm-2022-0186. Epub 2023 May 11. |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006571 |
| Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D013812 | Therapeutics |