Clinical trial NCT02465593: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Rectal Cancer
Lead sponsor: PharmaEngine
Sponsor class: INDUSTRY
First posted: 2015-06-08
Enrollment: 32
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: safety profile /the Dose Limiting Toxicity (DLT)
timeFrame: up to 36 months
measure: the recommended volume (dose)
timeFrame: up to 36 months
measure: anti-tumor activity
timeFrame: up to 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Hospital
Study officials:
affiliation: Kaohsiung Municipal United Hospital
name: Jwa-Yuan Wang, phD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.