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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02465593
Recruitment Status : Recruiting
First Posted : June 8, 2015
Last Update Posted : March 10, 2021
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Rectal Cancer Drug: PEP503 Drug: 5-fluorouracil Drug: capecitabine Procedure: surgical resection Radiation: Radiotherapy Phase 1 Phase 2

Detailed Description:
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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of PEP503 (Radioenhancer) With Radiotherapy, in Combination With Concurrent Chemotherapy for Patients With Locally Advanced or Unresectable Rectal Cancer
Study Start Date : June 2015
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: PEP503+5-FU/capecitabine+Radiotherapy
Patients will receive PEP503 given as intratumor injection on Day 1, followed by preoperative radiation therapy.
Drug: PEP503
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.
Other Name: NBTXR3

Drug: 5-fluorouracil
225 mg/m2 a day, 5 days/week for 5 weeks during radiotherapy period
Other Name: 5-FU

Drug: capecitabine
825 mg/m2 BID 5 days/week for 5 weeks during the radiotherapy period
Other Name: Xeloda

Procedure: surgical resection
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.

Radiation: Radiotherapy
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.

Primary Outcome Measures :
  1. safety profile /the Dose Limiting Toxicity (DLT) [ Time Frame: up to 36 months ]
    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

  2. the recommended volume (dose) [ Time Frame: up to 36 months ]
    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

  3. anti-tumor activity [ Time Frame: up to 36 months ]
    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

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02465593

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Contact: Jwa-Yuan Wang, phD 886-7-3121101 ext 5575

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Kaohsiung Medical University Hospital Recruiting
Kaohsiung City, Taiwan
Sponsors and Collaborators
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Principal Investigator: Jwa-Yuan Wang, phD Kaohsiung Municipal United Hospital
Publications of Results:
Other Publications:
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Responsible Party: PharmaEngine Identifier: NCT02465593    
Other Study ID Numbers: PEP503-RC-1001
First Posted: June 8, 2015    Key Record Dates
Last Update Posted: March 10, 2021
Last Verified: March 2021
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs