Altered Chemotherapy Sequencing During Neoadjuvant Therapy for Patients With Stage II or III Rectal Adenocarcinoma

NCT01302613 | Withdrawn Phase 1 DMC

• 1 other identifier: STU 082010-335
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the pilot portion of this study is to establish the safety and tolerability of an extended treatment break period in patients who have undergone neoadjuvant chemoradiotherapy as well as use of systemic therapy during this break.

Conditions

Stage II Rectal Cancer; Stage III Rectal Cancer

Keywords

rectal cancer

Outcome Measures

Primary Outcomes (1)

• The primary study endpoint for the phase I portion of this study is to assess surgical complications through the Clavien grading system.

  The adverse events will be followed prospectively from the date of surgery for 90 days. Dose-limiting toxicity (DLT) will be defined as \> grade 3 anastomotic stricture or leak, infection (including pelvic abscess or wound infection), small bowel obstruction, or fistualization. Any other post-operative complication thought related directly to the surgical intervention that is a grade 3 or higher Clavien complication will also be considered dose-limiting toxicity.

  90 days

Secondary Outcomes (1)

• The primary endpoint of the phase II portion of the study is complete pathologic response.

  9 to 11 weeks

Study Arms (1)

arm one

OTHER

RT + Chemo + surgery

Drug: Capecitabine; Drug: 5-FU; Drug: Leucovorin; Drug: Oxaliplatin; Radiation: radiation; Procedure: total mesorectal excision

Interventions

Capecitabine DRUG

Capecitabine will be delivered concurrently with the radiation therapy, at a dose of 1650 mg/m2 divided in even BID doses. It will only be taken on the days of radiation treatment (Monday-Friday, except for holidays). The A.M. dose of the capecitabine must be taken at least one hour prior to the radiation treatment.

arm one

5-FU DRUG

5-FU 400 mg/m2, iv bolus on day 1 followed by 2400 mg/m2 iv over 46 hours of each cycle. A cycle is delivered every two weeks. Three cycles will be given prior to the surgery. Five additional cycles will be given after surgery.

arm one

Leucovorin DRUG

Leucovorin 400 mg/m2, IV, over 2 hours before 5-FU on day 1 of each cycle. A cycle is delivered every two weeks. Three cycles will be given prior to the surgery. Five additional cycles will be given after surgery.

arm one

Oxaliplatin DRUG

Oxaliplatin 85mg/m2 IV on day 1 of each cycle. A cycle is delivered every two weeks. Three cycles will be given prior to the surgery. Five additional cycles will be given after surgery.

arm one

radiation RADIATION

28-30 fractions of radiation, given once a day, five days per week (Monday-Friday, except for holidays). The prescribed fraction dose is 180 cGy; the total radiation dose is thus 5040-5400 cGy. The primary treatment fields will be treated with 25 fractions of 180 cGy/fraction with a "boost" of 3-5 fractions of 180 cGy subsequently delivered.

arm one

total mesorectal excision PROCEDURE

Optimal surgical technique involving use of total mesorectal excision (TME) is mandated. The type of surgery, either low anterior resection with sparing of the sphincter mechanism or sphincter-eliminating abdominoperineal resection (APR), will be at the discretion of the attending surgeon.

arm one

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed study-specific informed consent form
• Age \> 18 years old
• Zubrod performance status 0-1
• Biopsy proven primary malignancy
• AJCC Stage II or III disease (T3-4 and/or N1-2 disease) as determined by endoscopic ultrasound and/or MRI staging
• Pretreatment rectal endoscopic ultrasound and pelvic MRI, colonoscopy, CT of chest, abdomen, and pelvis, and laboratory values as discussed below

You may not qualify if:

• History of inflammatory bowel disease
• Previous pelvic radiotherapy
• A major psychiatric illness which would limit understanding of the proposed protocol treatment and consent process.
• Men and women of reproductive potential must agree to use an effective contraception method
• Pregnant or lactating women
• Severe, active co-morbidity, defined as
• Unstable angina and/or CHF requiring hospitalization within the last six months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Presence of metastatic disease, including liver metastases
• Laboratory values out of range

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Fluorouracil; Leucovorin; Oxaliplatin; Radiation

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Physical Phenomena

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2011
• First Posted: February 24, 2011
• Study Start: March 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: August 20, 2020

Record last verified: 2019-02

Locations

US (1)