Complete Neoadjuvant Treatment for REctal Cancer (CONTRE)

This study has been completed.
Sponsor:
Collaborators:
Memorial Hospital of Rhode Island
Rhode Island Hospital
The Miriam Hospital
Information provided by (Responsible Party):
William Sikov, Brown University
ClinicalTrials.gov Identifier:
NCT01363843
First received: May 26, 2011
Last updated: April 21, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Rectal Cancer
Drug: Study Arm only (modified FOLFOX6)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Complete Neoadjuvant Treatment for REctal Cancer (CONTRE)

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • Incidence of complete resection [ Time Frame: approx 6 months ] [ Designated as safety issue: No ]
    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:
  • Evaluate the toxicity of study therapy [ Time Frame: approx 1 year ] [ Designated as safety issue: Yes ]

    Evaluate the toxicity of induction FOLFOX and subsequent infusional 5-FU or capecitabine/radiation.

    •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



Enrollment: 39
Study Start Date: May 2010
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: study arm only

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 with either continuous infusion 5-FU or capecitabine (MD choice)

  1. 5-FU 225 mg/m2 by continuous infusion starting the morning of the first dose of radiation and ending the morning after the last dose of radiation
  2. Capecitabine 825 mg/m2 PO BID

50.4 Gy Radiation in 28 fractions (45 Gy IMRT, 5.4 Gy 3D conformal boost)

Drug: Study Arm only (modified FOLFOX6)

Induction;FOLFOX6 - Oxaliplatin 85 mg/m2 + Leucovorin 400 mg/m2 IV 5-FU 400 mg/m2 IV followed 5-FU 2400 mg/m2 IV by continuous over 46 hours q 14 days x 8 cycles Concurrent Chemoradiation with either continuous infusion 5-FU or capecitabine (MD choice)

  1. 5-FU 225 mg/m2 by continuous infusion(typical week of treatment is Monday AM thru Saturday AM = 1125 mg/m2/week)
  2. Capecitabine 825 mg/m2 PO BID (typical week of treatment is Sunday PM thru Friday AM = 10 doses) 50.4 Gy Radiation in 28 fractions (45 Gy IMRT, 5.4 Gy 3D conformal boost)

Surgery

Other Names:
  • Eloxatin
  • Calcium Leucovorin
  • Citrovorum Factor
  • Folinic Acid
  • Adrucil
  • Carac
  • Efudix
  • Efudex
  • fluoroplex

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patients must have histologically proven adenocarcinoma of the rectum with no evidence of distant metastases.
  • The tumor must be clinically Stage II (T3-4 N0 with N0 being defined as all imaged lymph nodes are < 1.0cm) or III (T1-4 N1-2 with the definition of a clinically positive node being any node > 1.0cm). Stage of the tumor may be determined by CT scan, endorectal ultrasound or MRI.
  • Patients must have no evidence of distant metastases including liver metastases, peritoneal seeding, or inguinal lymphadenopathy.
  • Patients must not have received prior chemotherapy or pelvic radiation for rectal cancer, or prior pelvic radiation for any other malignancy that would prevent the patient from receiving the required radiation treatments for this study.
  • Patients must have a life expectancy of 5 years, excluding their diagnosis of cancer (as determined by the investigator).
  • Patients must not have an active concurrent invasive malignancy. Patients with prior malignancies, including invasive colon cancer, are eligible if they are deemed by their physician to be at low risk for recurrence. Patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 5 years prior to randomization.
  • Patients must be > 18 years of age, ECOG performance status 0-1.
  • ANC > 1,500/µl, platelets > 100,000/µl, total bilirubin < 2.0 mg/dl or direct bilirubin < 1.0 mg/dl, alkaline phosphatase < 3xULN, ALT < 3xULN, creatinine < 1.5xULN.
  • The patient must have been evaluated by a surgeon, radiation oncologist and medical oncologist and all must concur that the patient is appropriate for this study.
  • Signed informed consent; able to comply with study and/or follow- up procedures
  • Peripheral neuropathy < grade 1

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01363843

Locations
United States, Rhode Island
Memorial Hospital
Pawtucket, Rhode Island, United States, 02860
Rhode Island Hospital
Providence, Rhode Island, United States, 02906
The Miriam Hospital
Providence, Rhode Island, United States, 02903
Sponsors and Collaborators
William Sikov
Memorial Hospital of Rhode Island
Rhode Island Hospital
The Miriam Hospital
Investigators
Principal Investigator: William Sikov, md Brown University
  More Information

No publications provided

Responsible Party: William Sikov, Priniciple Investigator, Brown University
ClinicalTrials.gov Identifier: NCT01363843     History of Changes
Other Study ID Numbers: BrUOG 224
Study First Received: May 26, 2011
Last Updated: April 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Brown University:
neoadjuvant
chemo/radiation
rectal cancer
rectum cancer
colon cancer
colorectal cancer

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Levoleucovorin
Capecitabine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antidotes
Protective Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014