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

This study has been terminated.
(Drug shortage)
Sponsor:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01302613
First received: February 21, 2011
Last updated: November 1, 2012
Last verified: October 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Stage II Rectal Cancer
Stage III Rectal Cancer
 Drug: Capecitabine
Drug: 5-FU
Drug: Leucovorin
Drug: Oxaliplatin
Radiation: radiation
Procedure: total mesorectal excision
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot and Phase II Study of Altered Chemotherapy Sequencing During Neoadjuvant Therapy for Patients With Stage II or III Rectal Adenocarcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • The primary study endpoint for the phase I portion of this study is to assess surgical complications through the Clavien grading system. [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • The primary endpoint of the phase II portion of the study is complete pathologic response. [ Time Frame: 9 to 11 weeks ] [ Designated as safety issue: No ]
    9 to 11 weeks after the completion of the initial chemoradiotherapy.


Enrollment: 2
Study Start Date: March 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
arm one
RT + Chemo + surgery
 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.
Drug: 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.
Drug: 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.
Drug: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01302613

Locations
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Jeffrey Meyer, MD UT Southwestern Medical Center Dallas
  More Information

No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01302613     History of Changes
Other Study ID Numbers: STU 082010-335
Study First Received: February 21, 2011
Last Updated: November 1, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
rectal cancer

Additional relevant MeSH terms:
Adenocarcinoma
Adenocarcinoma, Mucinous
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
 Intestinal Diseases
Rectal Diseases
Leucovorin
Levoleucovorin
Oxaliplatin
Capecitabine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antidotes
Protective Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 23, 2013