Rectal CancerPhase 1/2NCT02465593
A Study of PEP503(Radio-enhancer) With Radiotherapy and Chemotherapy for Patients With Rectal Cancer
A Phase 1/2 study testing PEP503, 5-fluorouracil and capecitabine in people with Rectal Cancer, run by PharmaEngine at 1 site in Taiwan.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- PEP503, 5-fluorouracil and capecitabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteTaiwan
- Study dates
- Jun 2015to 28 Jul 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Rectal Cancer
- Being tested
- PEP503, 5-fluorouracil, capecitabine, surgical resection, Radiotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEP503Drug
Also called NBTXR3
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.
5-fluorouracilDrug
Also called 5-FU
225 mg/m2 a day, 5 days/week for 5 weeks during radiotherapy period
capecitabineDrug
Also called Xeloda
825 mg/m2 BID 5 days/week for 5 weeks during the radiotherapy period
surgical resectionProcedure or surgery
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.
RadiotherapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| PEP503+5-FU/capecitabine+Radiotherapy | Experimental | Patients will receive PEP503 given as intratumor injection on Day 1, followed by preoperative radiation therapy. Receives: Drug: PEP503; Drug: 5-fluorouracil; Drug: capecitabine; Procedure: surgical resection; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2015 (estimated)
- Study startJun 2015
- Primary completion28 Jul 2021
- Study completion28 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaEngine
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jwa-Yuan Wang, phD, Principal investigator, Kaohsiung Municipal United Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02465593
- Sponsor's protocol ID
- PEP503-RC-1001
- Status last verified
- Dec 2021
- First submitted
- 1 Jun 2015
- Last updated
- 11 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 2425199Colorectal 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.
PubMed 11684209Lubowski 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.
PubMed 25732387Tural 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.
PubMed 24218281Nel 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.
PubMed 19525947Huang 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.
PubMed 40255171Huang 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.
PubMed 37166053
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02465593
- Acronym / sponsor ID
- PEP503-RC-1001
- Conditions
- Rectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 32 participants (actual)
- Lead sponsor
- PharmaEngineIndustry (pharma, biotech, devices)
- Study start
- Jun 2015
- Primary completion
- 28 Jul 2021 (actual)
- Study completion
- 28 Jul 2021 (actual)
- First posted
- 8 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PEP503+5-FU/capecitabine+Radiotherapy | Experimental | Drug: PEP503, Drug: 5-fluorouracil, Drug: capecitabine, Procedure: surgical resection, Radiation: RadiotherapyPatients will receive PEP503 given as intratumor injection on Day 1, followed by preoperative radiation therapy. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEP503Also: NBTXR3The 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. | Drug | PEP503+5-FU/capecitabine+Radiotherapy |
| 5-fluorouracilAlso: 5-FU225 mg/m2 a day, 5 days/week for 5 weeks during radiotherapy period | Drug | PEP503+5-FU/capecitabine+Radiotherapy |
| capecitabineAlso: Xeloda825 mg/m2 BID 5 days/week for 5 weeks during the radiotherapy period | Drug | PEP503+5-FU/capecitabine+Radiotherapy |
| surgical resectionApproximately 8 weeks after the completion of chemoradiotherapy, surgical resection of the tumor (total mesorectal excision, TME) will be performed once the tumor become resectable. | Procedure or surgery | PEP503+5-FU/capecitabine+Radiotherapy |
| RadiotherapyIntensity-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. | Radiation | PEP503+5-FU/capecitabine+Radiotherapy |
Primary outcome
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
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
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
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2022.
- Background: PubMed 2425199Heald 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.
- Background: PubMed 11684209Colorectal 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.
- Background: PubMed 25732387Lubowski 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.
- Background: PubMed 24218281Tural 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.
- Results publication: PubMed 19525947Nel 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.
- Derived from this study: PubMed 40255171Huang 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.
- Derived from this study: PubMed 37166053Huang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jwa-Yuan Wang, phD principal investigator
Kaohsiung Municipal United Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PEP503, 5-fluorouracil and capecitabine in people with Rectal Cancer, run by PharmaEngine at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety profile /the Dose Limiting Toxicity (DLT) (time frame: up to 36 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02465593, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.