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

Primary Purpose

Rectal Cancer

Status

Terminated

Phase

Phase 1

Locations

Taiwan

Study Type

Interventional

Intervention

PEP503

5-fluorouracil

capecitabine

surgical resection

Radiotherapy

About this trial

This is an interventional treatment trial for Rectal Cancer

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Kaohsiung Medical University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PEP503+5-FU/capecitabine+Radiotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

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

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

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02465593

First Posted

June 1, 2015

Last Updated

December 17, 2021

Sponsor

PharmaEngine

1. Study Identification

Unique Protocol Identification Number

NCT02465593

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Terminated

Study Start Date

June 2015 (undefined)

Primary Completion Date

July 28, 2021 (Actual)

Study Completion Date

July 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PharmaEngine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PEP503+5-FU/capecitabine+Radiotherapy

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

PEP503

Other Intervention Name(s)

NBTXR3

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

5-fluorouracil

Other Intervention Name(s)

5-FU

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

capecitabine

Other Intervention Name(s)

Xeloda

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

surgical resection

Intervention Description

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.

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Description

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 Measure Information:

Title

safety profile /the Dose Limiting Toxicity (DLT)

Description

Time Frame

up to 36 months

Title

the recommended volume (dose)

Description

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

Time Frame

up to 36 months

Title

anti-tumor activity

Description

Time Frame

up to 36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jwa-Yuan Wang, phD

Organizational Affiliation

Kaohsiung Municipal United Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Kaohsiung Medical University Hospital

City

Kaohsiung City

Country

Taiwan

12. IPD Sharing Statement

Citations:

PubMed Identifier

2425199

Citation

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.

Results Reference

background

PubMed Identifier

11684209

Citation

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.

Results Reference

background

PubMed Identifier

25732387

Citation

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.

Results Reference

background

PubMed Identifier

24218281

Citation

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.

Results Reference

background

PubMed Identifier

19525947

Citation

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.

Results Reference

result

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

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