Trial of Chemoradiation and Pembrolizumab in Patients With Rectal Cancer

Rectal Cancer Clinical Trial

Official title: A Phase II Trial of Neoadjuvant Chemoradiation (CRT) and Pembrolizumab in Patients With Rectal Cancer: Hoosier Cancer Research Network GI15-213

Status Withdrawn

Clinical Trial Summary

This is a phase II, prospective open label multi-center study in which subjects with stage II-III rectal cancer will be accrued in order to determine the pathological complete response rate of neoadjuvant pembrolizumab in combination with chemoradiation treatment (CRT). Subjects must have a diagnosis of rectal cancer, stage II (T3-4, N0) or stage III (any T, N1-2). Subjects must have received no prior treatments (chemotherapy, pelvic radiation or surgery) for their rectal cancer.

Eligible subjects will receive standard chemoradiation with pembrolizumab administered every 3 weeks on days 1, 22, and 43 of the neoadjuvant interval. In all subjects, restaging endorectal or pelvic MRI with chest and abdominal CT will be performed at 6-8 weeks after completion of neoadjuvant treatment to determine resectability and to rule out any evidence of metastases. Subjects who have resectable disease will undergo surgery within 2-4 weeks of imaging; 8-12 weeks after completion of chemoradiation. Subjects who are found to have unresectable or metastatic disease post treatment with the combination of CRT+ pembrolizumab should receive standard of care definitive treatment per the discretion of their treating physician.

Clinical Trial Description

OUTLINE: This is a multi-center study.

NEOADJUVANT TREATMENT:

All subjects will receive concurrent chemoradiation and pembrolizumab neoadjuvant treatment for 6 weeks:

• Pembrolizumab 200 mg Intravenously (IV) Days 1, 22 and 43

• Capecitabine 825 mg/m2 PO (by mouth) in twice daily doses (daily total 1650 mg/m2) on 5 consecutive days / week Monday-Friday given on the radiation days for 28 days

• Radiation 50.4 Gy (Gray) in daily fractions of 1.8 Gy over a 6 week interval,excludes weekends

POST NEOADJUVANT TREATMENT:

• End of treatment (EOT) 6-8 weeks after last dose of neoadjuvant treatment, all subjects will be assessed to determine resectability. Those with resectable disease will undergo surgery within 2-4 weeks of imaging, 8-12 weeks after completion of chemoradiation. Subjects who are found to have unresectable or metastatic disease post treatment with the combination of CRT+ pembrolizumab should receive standard of care definitive treatment per the discretion of their treating physician.

• Surgical Resection ( 2-4 weeks after restaging imaging and 8-12 weeks after completion of chemoradiation)

• Follow Up

• Post Operative Visit (4-6 weeks after surgery)

• Disease Follow Up -Years 1-2 (per site investigator discretion; suggested every 3-6 months)

• Survival Follow Up - Years 3-5

To demonstrate adequate organ function, all screening labs should be performed within 7 days of treatment initiation:

Hematological:

• Absolute neutrophil count (ANC) ≥1,500 /mcL

• Platelets ≥100,000 / mcL

• Hemoglobin ≥9 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)

Renal:

• Serum creatinine ≤1.5 X upper limit of normal (ULN) OR

• Measured or calculated creatinine clearance ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl

Hepatic:

• Serum total bilirubin ≤ 1.5 X ULN

• Aspartate transaminase (AST) / Serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 X ULN

• Alanine aminotransferase (ALT) / Serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 X ULN

• Albumin ≥2.5 mg/dL

Coagulation:

• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants)

• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy (as long as PT or PTT is within therapeutic range of intended use of anticoagulants) ;

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasm
• Rectal Neoplasms

• NCT number: NCT02586610
• Study type: Interventional
• Source: Hoosier Cancer Research Network
• Status: Withdrawn
• Phase: Phase 2
• Start date: October 2016
• Completion date: December 2020