Locally-Advanced Rectal Adenocarcinoma Locally Advanced Rectal Cancer
Conditions
Interventions
Visit 1
1. Informed consent
2. Baseline laboratory tests including free T4, TSH, Hepatitis B virus surface antigen, and Hepatitis C virus antibodies
3. Tissue blocks or at least 7 slides of the base
Day 1-5)
1. SCRT will be administered for 5 days from day 1 (D1) to D5 during week 1 (Either 3D conformal or in intensity-modulated radiotherapy (IMRT) treatment planning may be used. The daily dose w
Day 10)
2. Sigmoidoscopy will be performed and a biopsy taken
3. Slides of the corresponding specimen will be provided
4. PD-L1 expression on tumor cells and TILs will be assessed by the pathologist
Day 15+)
1. mFOLFOX-6 chemotherapy plus avelumab will be administered every 2 weeks for 6 cycles.
Visits 2-6
Visit 7
Visits 8-13
Visit 13
Visit 14
Sponsors
American University of Beirut
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1) Signed informed consent form. 2) Patients aged =18 years. 3) Locally-advanced rectal cancer cT2 N1-3, cT3 N0-3 4) < 12 cm from anal verge. 5) Histologically proven rectal adenocarcinoma. 6) ECOG performance score = 1. 7) Have adequate organ function by meeting the following: • Absolute neutrophil count (ANC) = 1.5 × 109/L; • Platelet count = 100 × 109/L; • Hemoglobin = 9 g/dL; • Total bilirubin level = 1.5 × the upper limit of normal (ULN) range; • AST and ALT levels = 2.5 × ULN or AST and ALT levels = 5 x ULN (for subjects with documented metastatic disease to the liver); • Estimated creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method). 8) Negative serum or urine pregnancy test at screening for women of childbearing potential.
Exclusion criteria
Exclusion criteria: Exclusion Criteria 1) Distant metastasis (M1). 2) Patients with T2 N0 or T4. 3) Recurrent rectal cancer. 4) Symptoms or history of peripheral neuropathy. 5) Prior radiotherapy or chemotherapy. 6) Current use of immunosuppressive medication except for the following: - Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); - Systemic corticosteroids at physiologic doses = 10 mg/day of prednisone or equivalent; - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 7) Concurrent treatment with a non-permitted drug. 8) Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. 9) Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines. 10) Active infection requiring systemic therapy. 11) Known history of testing positive for the human immunodeficiency virus or known acquired immunodeficiency syndrome. 12) Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive). 13) Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade = 3). 14) Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke ( 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable. 16) Prior organ transplantation including allogenic stem-cell transplantation. 17) Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: The primary efficacy endpoint is the proportion of patients who achieve a pathological complete response, defined as no viable tumor cells on the resected specimen.;Timepoints: The primary efficacy endpoint is the proportion of patients who achieve a pathological complete response, defined as no viable tumor cells on the resected specimen.;Measure: The primary efficacy endpoint is the proportion of patients who achieve a pathological complete response, defined as no viable tumor cells on the resected specimen. | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: The secondary efficacy endpoints are: 1) PFS at 3 years will be estimated with the Kaplan-Meier method and presented with the 95% CI. 2) Evaluation of response by obtaining TRG just after surgery (week 16 or 17 ± 3 days).;Timepoints: The secondary efficacy endpoints are: 1) PFS at 3 years will be estimated with the Kaplan-Meier method and presented with the 95% CI. 2) Evaluation of response by obtaining TRG just after surgery (week 16 or 17 ± 3 days).;Measure: The secondary efficacy endpoints are: 1) PFS at 3 years will be estimated with the Kaplan-Meier method and presented with the 95% CI. 2) Evaluation of response by obtaining TRG just after surgery (week 16 or 17 ± 3 days). | — |
Countries
Jordan, Lebanon
Contacts
Public ContactAli Shamseddine
American University of Beirut Medical Center
Outcome results
None listed