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

• ClinicalTrials.gov Identifier: NCT01060007
• Recruitment Status: Completed
• First Posted: February 1, 2010
• Results First Posted: February 10, 2015
• Last Update Posted: March 8, 2017
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

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.

Condition or disease	Intervention/treatment	Phase
Rectal Neoplasms	Radiation: External beam radiation; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-FU; Drug: Capecitabine	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer
• Study Start Date: November 2009
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: September 2014

Arms and Interventions

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.

Radiation: External beam radiation; Drug: Oxaliplatin; Other Name: Eloxatin; Drug: Leucovorin; Drug: 5-FU; Other Names: Fluorouracil; Efudex; Drug: Capecitabine; Other Name: Xeloda

Outcome Measures

Primary Outcome Measures :

1. 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).
2. 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

Secondary Outcome Measures :

1. 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) ]
2. Incidence of Post Chemoradiotherapy Grade 3 or Higher Morbidity [ Time Frame: 1 year (completion of all treatment) ]
3. Local Control [ Time Frame: 30 months ]
   • Kaplan-Meier projections
   • Local control = control of primary tumor
4. Rate of Overall Control [ Time Frame: 1 year ]
5. Rate of Locoregional Control [ Time Frame: 1 year ]
6. Freedom From Disease Relapse [ Time Frame: 30 months ]
   Kaplan-Meier projections.
7. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

St. Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Investigators

• Principal Investigator: Parag Parikh, M.D.; Washington University School of Medicine

More Information

Additional Information:

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

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01060007
• Other Study ID Numbers: 09-0696 / 201106272
• First Posted: February 1, 2010
• Results First Posted: February 10, 2015
• Last Update Posted: March 8, 2017
• Last Verified: January 2017

Additional relevant MeSH terms:

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Leucovorin; Fluorouracil; Capecitabine; Oxaliplatin; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antidotes; Protective Agents; Vitamin B Complex; Vitamins; Micronutrients