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

Primary Purpose

Rectal Neoplasms

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

External beam radiation

Oxaliplatin

Leucovorin

5-FU

Capecitabine

About this trial

This is an interventional treatment trial for Rectal Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant radiation followed by FOLFOX

Arm Description

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.

Outcomes

Primary Outcome Measures

Rate of T Stage Downstaging

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).

Preoperative Gastrointestinal Morbidity

As measured by participants who experience grade 3 or higher gastrointestinal morbidity

Secondary Outcome Measures

Incidence of Any Late Grade 3 or Higher Morbidity

Incidence of Post Chemoradiotherapy Grade 3 or Higher Morbidity

Local Control

Kaplan-Meier projections Local control = control of primary tumor

Rate of Overall Control

Rate of Locoregional Control

Freedom From Disease Relapse

Kaplan-Meier projections.

Determine Quality of Anorectal Function

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.

Full Information

NCT ID

NCT01060007

First Posted

January 28, 2010

Last Updated

January 24, 2017

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT01060007

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

April 2013 (Actual)

Study Completion Date

September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

80 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant radiation followed by FOLFOX

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

External beam radiation

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Other Intervention Name(s)

Eloxatin

Intervention Type

Drug

Intervention Name(s)

Leucovorin

Intervention Type

Drug

Intervention Name(s)

5-FU

Other Intervention Name(s)

Fluorouracil, Efudex

Intervention Type

Drug

Intervention Name(s)

Capecitabine

Other Intervention Name(s)

Xeloda

Primary Outcome Measure Information:

Title

Rate of T Stage Downstaging

Description

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).

Time Frame

Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)

Title

Preoperative Gastrointestinal Morbidity

Description

As measured by participants who experience grade 3 or higher gastrointestinal morbidity

Time Frame

Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)

Secondary Outcome Measure Information:

Title

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)

Title

Incidence of Post Chemoradiotherapy Grade 3 or Higher Morbidity

Time Frame

1 year (completion of all treatment)

Title

Local Control

Description

Kaplan-Meier projections Local control = control of primary tumor

Time Frame

30 months

Title

Rate of Overall Control

Time Frame

1 year

Title

Rate of Locoregional Control

Time Frame

1 year

Title

Freedom From Disease Relapse

Description

Kaplan-Meier projections.

Time Frame

30 months

Title

Determine Quality of Anorectal Function

Description

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.

Time Frame

Up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Parag Parikh, M.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.siteman.wustl.edu

Description

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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