Complete Neoadjuvant Treatment for REctal Cancer (CONTRE)

Phase 2

Completed

Conditions: Colon Cancer
Rectal Cancer

Interventions: Drug: FOLFOX6
Radiation: RT with concurrent chemotherapy
Procedure: Surgery

Registration Number: NCT01363843

Lead Sponsor: William Sikov MD

Brief Summary: The purpose of this study is to find out how well patients with cancer of the rectum do if they get all of their other treatment - chemotherapy by itself followed by chemotherapy and radiation together - before surgery. Patients have recently been diagnosed with rectal cancer, and the doctors have recommended neo-adjuvant chemo treatment to try to shrink the cancer before removing it.

Detailed Description: The goals of treatment of locally advanced (T3-4 or N1-2) rectal cancer are to eliminate the primary tumor and any involved adjacent lymph nodes, minimize the risk of distant recurrence, and, when possible, preserve anal sphincter function. Standard treatment consists of surgery, concurrent chemotherapy and radiation (RT) and adjuvant chemotherapy. As the present time, the chemoradiation portion of the treatment is often administered before, as opposed to following, surgical resection. This approach has been associated with tumor down-staging, leading to higher rates of tumor resectability and an increase in the ability to perform sphincter-saving surgeries. (1). However, while advances in treatment of the primary tumor and regional nodes, specifically administration of preoperative chemoradiation and more aggressive surgical approaches, such as total mesorectal excision (TME), have been shown to improve locoregional disease control, toxicities and complications of these treatments may result in delay or omission of adjuvant chemotherapy, which could increase the risk of distant recurrence. In this pilot study, standard adjuvant chemotherapy (8 cycles of modified FOLFOX6) will be administered prior to chemoradiation and definitive surgery, eliminating the need for post-operative systemic therapy. The investigators will evaluate the ability of patients to tolerate this treatment and its impact on achievement of pathologic complete responses (pCRs), negative surgical margins and sphincter preservation.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 39

Inclusion Criteria

Not provided

Exclusion Criteria

Evidence of metastatic disease.
Rectal cancers other than adenocarcinoma, i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, cloacogenic carcinoma, etc.
Pregnancy or lactation at the time of proposed randomization. Eligible patients of reproductive potential (both sexes) must agree to use adequate contraception.
Any therapy for this cancer prior to randomization.
Synchronous invasive colon cancer.
Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient from receiving any chemotherapy treatment option or would prevent required follow-up.
Patients with active inflammatory bowel disease, abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0 or other serious medical illness which might limit the ability of the patient to receive protocol therapy.
Prior pelvic irradiation for any indication.
Known hypersensitivity to 5-fluorouracil or oxaliplatin
Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment	FOLFOX6	Induction therapy - Modified FOLFOX6 - Oxaliplatin 85 mg/m2 + Leucovorin 400 mg/m2 IV, followed by 5-FU 400 mg/m2 IV, followed 5-FU 2400 mg/m2 IV by continuous infusion over 46 hours - Repeat q14 days x 8 cycles Concurrent Chemoradiation 50.4 Gy Radiation in 28 fractions (45 Gy IMRT, 5.4 Gy 3D conformal boost) Surgery
treatment	RT with concurrent chemotherapy	Induction therapy - Modified FOLFOX6 - Oxaliplatin 85 mg/m2 + Leucovorin 400 mg/m2 IV, followed by 5-FU 400 mg/m2 IV, followed 5-FU 2400 mg/m2 IV by continuous infusion over 46 hours - Repeat q14 days x 8 cycles Concurrent Chemoradiation 50.4 Gy Radiation in 28 fractions (45 Gy IMRT, 5.4 Gy 3D conformal boost) Surgery
treatment	Surgery	Induction therapy - Modified FOLFOX6 - Oxaliplatin 85 mg/m2 + Leucovorin 400 mg/m2 IV, followed by 5-FU 400 mg/m2 IV, followed 5-FU 2400 mg/m2 IV by continuous infusion over 46 hours - Repeat q14 days x 8 cycles Concurrent Chemoradiation 50.4 Gy Radiation in 28 fractions (45 Gy IMRT, 5.4 Gy 3D conformal boost) Surgery

Primary Outcome Measures

Name	Time	Method
Incidence of Complete Resection	approx 6 months	The primary objective of this study is to determine the incidence of pCRs and complete (R0) resections at surgery after induction chemotherapy with 8 cycles of modified FOLFOX6 followed by standard chemoradiation with IMRT with concurrent infusional 5-FU or capecitabine

Secondary Outcome Measures

Name	Time	Method
Evaluate the Toxicity of Study Therapy	approx 1 year	Evaluate the toxicity of induction FOLFOX and subsequent infusional 5-FU or capecitabine/radiation. Results show number of patients who experienced a SAE. This does not mean all SAEs were deemed related to treatment. •Secondary efficacy measures include the clinical response rate, as measured endorectal ultrasound or pelvic MRI, and incidence and severity of toxicities seen during the various phases of study treatment, including treatment delays, bleeding and post-op complications. Each visit will have a toxicity assessment completed

Trial Locations

Locations (3): Memorial Hospital
🇺🇸
Pawtucket, Rhode Island, United States
The Miriam Hospital
🇺🇸
Providence, Rhode Island, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States