Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Active, not recruiting; Phase 2

Conditions: Rectal Cancer

Treatments: Drug: Capecitabine (Xeloda®); Drug: Leucovorin; Drug: 5-Fluorouracil (5-FU); Behavioral: Quality of Life Questionnaires; Radiation: intensity modulated radiotherapy (IMRT); Procedure: DRE-Endoscopy; Drug: Oxaliplatin (OXAL)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02008656

13-213

Details and patient eligibility

About

The study is designed to test the hypothesis that patients with Locally advanced rectal cancer ( LARC) treated with Total neoadjuvant therapy (TNT) and Total mesorectal excision (TME) or Non-operative management (NOM) will have an improved 3-year disease-free survival (DFS) compared to patients with similar tumors treated with Chemoradiation therapy (CRT), Total mesorectal excision (TME) and Adjuvant chemotherapy (ACT).

Enrollment: 358 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed diagnosis of adenocarcinoma of the rectum
• Clinical Stage II (T3-4, N-) or Stage III (any T, N+) based on MRI
• Rectal tumor at baseline which would be considered to require complete TME
• No evidence of distant metastases
• No prior pelvic radiation therapy
• No prior chemotherapy or surgery for rectal cancer
• Age ≥ 18 years The minimum legal age of consent for select Canadian provinces is 19
• No active infections requiring systemic antibiotic treatment (oral antibiotics are acceptable at the discretion of the treating physician)
• ECOG Performance status 0-2
• Women with childbearing potential (WOCBP) who are negative for pregnancy test (urine or blood) and who agree to use effective contraceptive method. A woman of childbearing potential is defined of one who is biologically capable of becoming pregnant. Reliable contraception should be used from trial screening and must be continued throughout the study.
• Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Patients who do not read or understand English are eligible and may be consented according to institutional and federal regulations.
• ANC > 1.5 cells/mm3, HGB > 8.0 gm/dl, PLT > 150,000/mm3 total bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's Syndrome who must have total bilirubin ≤ 3.0 x ULN), AST≤ 3 x ULN, ALT ≤ 3 x ULN.

Exclusion criteria

• Recurrent rectal cancer
• Primary unresectable rectal cancer. A tumor is considered unresectable when invading adjacent organs and an en block resection will not achieve negative margins.
• Creatinine level greater than 1.5 times the upper limit of normal.
• Patients who have received prior pelvic radiotherapy.
• Patients who are unable to undergo an MRI.
• Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
• Patients with a history of venous thrombotic episodes such as deep venous thrombosis, pulmonary embolus occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Similarly, patients who are anticoagulated for atrial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy.
• Other Anticancer or Experimental Therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
• WOCBP who are unwilling or unable to use an acceptable method of avoiding pregnancy for the entire study period.
• Women who are pregnant or breast-feeding.
• Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment, would make them inappropriate candidates for entry into this study.
• Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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358 participants in 2 patient groups

INCT

Experimental group

Description:

Arm 1 will receive chemotherapy before chemoradiation. This is called induction neoadjuvant chemotherapy arm (INCT). The neoadjuvant chemotherapy regimen is prescribed specifically as 8 cycles of FOLFOX or 5 cycles of CapeOX over a period of approximately 15-16 weeks. Endoscopic exam (2-4 wks) after chemotherapy. If stable or response then pt will have radiation with either 5-FU or capecitabine.

Treatment:

Drug: Oxaliplatin (OXAL)

Procedure: DRE-Endoscopy

Behavioral: Quality of Life Questionnaires

Radiation: intensity modulated radiotherapy (IMRT)

Drug: Capecitabine (Xeloda®)

Drug: Leucovorin

Drug: 5-Fluorouracil (5-FU)

CNCT

Experimental group

Description:

Arm 2 will receive chemoradiation before chemotherapy This is called the consolidation neoadjuvant chemotherapy arm (CNCT). Pt will have 6 weeks of chemoradiation therapy. Along with the radiation the pt will receive either 5-FU or capecitabine. 2-4 weeks after pt will have endoscopic exam and if stable or response pt will have will have 8 cycles of FOLFOX or 6 cycles of CapeOX.

Treatment:

Drug: Oxaliplatin (OXAL)

Procedure: DRE-Endoscopy

Behavioral: Quality of Life Questionnaires

Radiation: intensity modulated radiotherapy (IMRT)

Drug: Capecitabine (Xeloda®)

Drug: Leucovorin

Drug: 5-Fluorouracil (5-FU)