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

Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02465593
• Other study ID #: PEP503-RC-1001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 2015
• Est. completion date: July 28, 2021

Study information

• Verified date: December 2021
• Source: PharmaEngine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: July 28, 2021
• Est. primary completion date: July 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

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.
• 5-fluorouracil
225 mg/m2 a day, 5 days/week for 5 weeks during radiotherapy period
• capecitabine
825 mg/m2 BID 5 days/week for 5 weeks during the radiotherapy period

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.

Locations

Country	Name	City	State
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung City

Sponsors (1)

Lead Sponsor	Collaborator
PharmaEngine

Country where clinical trial is conducted

Taiwan, 

References & Publications (5)

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. — View Citation

Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986 Jun 28;1(8496):1479-82. — View 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. — View Citation

Nel AE, Mädler 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. Review. — View Citation

Tural D, Selcukbiricik F, Yildiz Ö, Elcin O, Erdamar S, Güney S, Demireli F, Büyükünal E, Serdengeçti 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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