Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

January 24, 2017 updated by: Washington University School of Medicine

A Phase II Evaluation of Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

To determine if short course radiotherapy followed by chemotherapy can maintain morbidity at or below levels reported with concurrent 5FU, oxaliplatin, and radiotherapy, while maintaining response rates comparable to what would be expected with radiotherapy and concurrent chemotherapy.

Study Overview

Detailed Description

Our principal objectives in this trial will be to determine if short course radiotherapy followed by chemotherapy can maintain morbidity at or below levels reported with concurrent 5FU (oral capecitabine if 5FU is unavailable), oxaliplatin, and radiotherapy, while maintaining response rates comparable to what would be expected with radiotherapy and concurrent chemotherapy. If we can establish a T stage downstaging rate that is significantly better than 50% and if acute tolerance is acceptable, then we would consider this study as having provided sufficient pilot data to support including this approach as an arm in a multi-institution phase III trial. The long-term goal is improved overall control of disease by delivering better chemotherapy earlier.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Biopsy proven adenocarcinoma of the rectum
  • Patient evaluated by surgeon and found to be a potential surgical candidate. Since the primary objectives are response to chemoradiation and acute toxicity, lesions which are initially unresectable are eligible-provided the surgeon feels that, if there is sufficient response, surgery could become feasible.
  • Clinical evidence of T3 or T4 disease. This can be by imaging studies (see or by physical findings (tethering on palpation for T3 lesions or invasion of a neighboring organ for T4 lesions)
  • Karnofsky Performance Status at >60
  • Laboratory criteria:
  • Absolute neutrophil count >= 1.5 K
  • Platelets >= 100 K
  • Total Bilirubin <= 2.0;
  • SGOT and Alkaline Phosphatase <= 2 x upper limit of normal
  • Creatinine < 2.0
  • Hemoglobin >= 8.0
  • Informed consent signed
  • Tumor measurable in at least one dimension. This may be, e.g. length and/or width measured endoscopically or on digital rectal examination, and maximum rectal wall thickness determined by imaging studies.
  • Estimated longevity at least 12 months
  • Patients with distant metastatic disease will be eligible if they satisfy all other conditions

Exclusion Criteria:

  • Pregnant women, children < 18 years, or patients unable to give informed consent
  • Patients with a past history of pelvic radiotherapy.
  • Patients with any other malignancy within the past 5 years except: skin cancer or in-situ cervical cancer
  • Patients with known allergy/intolerance to 5FU, Leucovorin, Oxaliplatin, Capecitabine
  • Prior chemotherapy for colorectal cancer.
  • Grade >= 2 peripheral neuropathy
  • Any condition which, in the opinion of the treating medical oncologist, renders the patient unfit for 5FU (oral capecitabine if 5FU is unavailable), Leucovorin, Oxaliplatin chemotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant radiation followed by FOLFOX

Radiation - 20 Gy in 5 fractions to regional nodes. 25 Gy in the same 5 fractions to macroscopic disease. This is given over 1 week.

FOLFOX Chemotherapy - after two weeks rest - oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 IV/2 hours followed sequentially by 5FU 400 mg/m2 IV push and 5FU 2400 mg/m2 over 46 hour CIVI. Repeat ever other week for a total of 4 courses (this equals 6 weeks).

If 5-FU is unavailable -- oral capecitabine can be given as 1000 mg/m2 BID on days 1-7 every 14 days.

Other Names:
  • Eloxatin
Other Names:
  • Xeloda
Other Names:
  • Fluorouracil
  • Efudex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of T Stage Downstaging
Time Frame: Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)
T stage downstaging is defined as clinical pretreatment American Joint Committee on Cancer T stage (cT) being greater than pathologic T stage at surgery (ypT).
Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)
Preoperative Gastrointestinal Morbidity
Time Frame: Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)
As measured by participants who experience grade 3 or higher gastrointestinal morbidity
Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Any Late Grade 3 or Higher Morbidity
Time Frame: Preoperative (mean time from start of radiation to surgery 17.3 weeks (SD +/- 2.9 weeks)
Preoperative (mean time from start of radiation to surgery 17.3 weeks (SD +/- 2.9 weeks)
Incidence of Post Chemoradiotherapy Grade 3 or Higher Morbidity
Time Frame: 1 year (completion of all treatment)
1 year (completion of all treatment)
Local Control
Time Frame: 30 months
  • Kaplan-Meier projections
  • Local control = control of primary tumor
30 months
Rate of Overall Control
Time Frame: 1 year
1 year
Rate of Locoregional Control
Time Frame: 1 year
1 year
Freedom From Disease Relapse
Time Frame: 30 months
Kaplan-Meier projections.
30 months
Determine Quality of Anorectal Function
Time Frame: Up to 1 year
Anorectal function was measured by the participant's response to the FACT-C questionnaire question "I have control of my bowels". The answers ranged from 0=not at all to 4=very much.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2009

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

January 28, 2010

First Submitted That Met QC Criteria

January 29, 2010

First Posted (Estimate)

February 1, 2010

Study Record Updates

Last Update Posted (Actual)

March 8, 2017

Last Update Submitted That Met QC Criteria

January 24, 2017

Last Verified

January 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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