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

Stage III Rectal Cancer Clinical Trial

Official title:

A Pilot and Phase II Study of Altered Chemotherapy Sequencing During Neoadjuvant Therapy for Patients With Stage II or III Rectal Adenocarcinoma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01302613
• Other study ID #: STU 082010-335
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: March 2011
• Est. completion date: November 2012

Study information

• Verified date: February 2019
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The proposed protocol aims to continue tumor-directed therapy during the typical "break period" in an effort to improve on both local tumor response as well as distant disease control. First, the duration from completion of chemoradiotherapy would increase from 6-8 weeks to 9-11 weeks. As noted above, this may allow for further cell death with resultant pathologic downstaging. Secondly, the protocol calls for continued systemic therapy during the 9-11 week period, thus allowing continuation of therapies directed towards both the primary as well as distant sites of disease. The primary aim of this pilot study would be to establish the feasibility of this intensified neoadjuvant approach, especially with respect to tolerability of the subsequent pelvic surgery. A subsequent phase II portion will evaluate the efficacy of this treatment approach.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed study-specific informed consent form

2. Age > 18 years old

3. Zubrod performance status 0-1

4. Biopsy proven primary malignancy

5. AJCC Stage II or III disease (T3-4 and/or N1-2 disease) as determined by endoscopic ultrasound and/or MRI staging

6. Pretreatment rectal endoscopic ultrasound and pelvic MRI, colonoscopy, CT of chest, abdomen, and pelvis, and laboratory values as discussed below

Exclusion Criteria:

1. History of inflammatory bowel disease

2. Previous pelvic radiotherapy

3. A major psychiatric illness which would limit understanding of the proposed protocol treatment and consent process.

4. Men and women of reproductive potential must agree to use an effective contraception method

5. Pregnant or lactating women

6. 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

7. Presence of metastatic disease, including liver metastases

8. Laboratory values out of range

Related Conditions & MeSH terms

• Adenocarcinoma
• Rectal Neoplasms
• Stage II Rectal Cancer
• Stage III Rectal Cancer

Intervention

Drug:
• Capecitabine
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.
• 5-FU
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.
• Leucovorin
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.
• Oxaliplatin
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.

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.

Procedure:
• total mesorectal excision
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.

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The primary endpoint of the phase II portion of the study is complete pathologic response.	9 to 11 weeks after the completion of the initial chemoradiotherapy.	9 to 11 weeks