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

A Phase Ib/II Study of PEP503 (Radioenhancer) With Radiotherapy, in Combination With Concurrent Chemotherapy for Patients With Locally Advanced or Unresectable Rectal Cancer

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.

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.

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:

  • 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

Exclusion Criteria:

• 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