NCT02586610

Trial of Chemoradiation and Pembrolizumab in Patients With Rectal Cancer

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

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Osama Rahma, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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)

Conditions

• Rectal Cancer
• Rectal Neoplasm

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab 200 mg IV Days 1, 22 and 43
DRUG	Capecitabine	Capecitabine 825 mg/m2 PO twice a day (daily total 1650 mg/m2) on 5 consecutive days / week M-F given on the radiation days for 28 days
RADIATION	Radiation Therapy	Radiation 50.4 GY in daily fractions of 1.8 Gy over a 6 week interval (excludes weekends)

Timeline

• Start date: 2016-10-01
• Primary completion: 2018-06-01
• Completion: 2020-12-01
• First posted: 2015-10-26
• Last updated: 2017-01-20