A Study of PEP503(Radio-enhancer) With Radiotherapy and Chemotherapy for Patients With Rectal Cancer

NCT02465593 | Terminated Phase 1 DMC

• 1 other identifier: PEP503-RC-1001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

• Escalation phase (Part Ib): A 3 + 3 dose escalation study design will be adopted in this phase to identify the recommended injection volume of PEP503 for intratumor injection.
• Expansion phase (Part II): Following the confirmation of the recommended volume of intratumor injection, 18 additional patients will be enrolled at the recommended volume level to evaluate for efficacy.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

PEP503+5-FU/capecitabine+Radiotherapy

EXPERIMENTAL

Patients will receive PEP503 given as intratumor injection on Day 1, followed by preoperative radiation therapy.

Drug: PEP503; Drug: 5-fluorouracil; Drug: capecitabine; Procedure: surgical resection; Radiation: Radiotherapy

Interventions

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.

Also known as: NBTXR3

PEP503+5-FU/capecitabine+Radiotherapy

5-fluorouracil DRUG

225 mg/m2 a day, 5 days/week for 5 weeks during radiotherapy period

Also known as: 5-FU

PEP503+5-FU/capecitabine+Radiotherapy

capecitabine DRUG

825 mg/m2 BID 5 days/week for 5 weeks during the radiotherapy period

Also known as: Xeloda

PEP503+5-FU/capecitabine+Radiotherapy

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.

PEP503+5-FU/capecitabine+Radiotherapy

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.

PEP503+5-FU/capecitabine+Radiotherapy

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• absolute neutrophil count (ANC) ≥ 1,500/mm3
• platelet count ≥ 100,000/mm3
• total bilirubin ≤ 1.5x the upper limit of normal (ULN)
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN
• alkaline phosphatase (ALP) ≤ 2.5 x ULN
• calculated creatinine clearance ≥ 50 mL/min, or creatinine within normal range
• 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

You may not qualify if:

• Prior history of pelvic radiation therapy
• Hypersensitivity to fluoropyrimidine
• Uncontrolled serious medical or psychiatric illness
• Myocardial infarction or uncontrolled angor pectoris (angina) within the prior 6 months
• No more than 4 weeks since prior participation in any investigational drug study
• Major surgery within 28 days
• Other malignancy within the past 3 years except effectively treated squamous cell or basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum
• Cardiovascular disease that would preclude study treatment or follow-up
• Informed consent not duly signed and dated to participate in the study

Sponsors & Collaborators

• PharmaEngine: lead

Study Sites (1)

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

Location

Related Publications (7)

• 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.

  PMID: 2425199 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.

  PMID: 11684209 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.

  PMID: 25732387 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.

  PMID: 24218281 BACKGROUND

• 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.

  PMID: 19525947 RESULT

• 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.

  PMID: 40255171 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.

  PMID: 37166053 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Fluorouracil; Capecitabine; Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Jwa-Yuan Wang, phD

  Kaohsiung Municipal United Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2015
• First Posted: June 8, 2015
• Study Start: June 1, 2015
• Primary Completion: July 28, 2021
• Study Completion: July 28, 2021
• Last Updated: January 11, 2022

Record last verified: 2021-12

Locations

TW (1)