Rectal Cancer
Conditions
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.
Interventions
DRUGPEP503
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.
DRUG5-fluorouracil
225 mg/m2 a day, 5 days/week for 5 weeks during radiotherapy period
DRUGcapecitabine
825 mg/m2 BID 5 days/week for 5 weeks during the radiotherapy period
PROCEDUREsurgical 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.
RADIATIONRadiotherapy
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.
Sponsors
PharmaEngine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| safety profile /the Dose Limiting Toxicity (DLT) | 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) | 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 | 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 |
Countries
Taiwan
Outcome results
None listed