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A Phase II Study for Short Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy (IMRT) in Combination With Capecitabine in Patients With Resectable Rectal Carcinoma

Phase 2
18 Years
75 Years
Open (Enrolling)

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Trial Information

A Phase II Study for Short Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy (IMRT) in Combination With Capecitabine in Patients With Resectable Rectal Carcinoma

Preoperative chemoradiotherapy has become a standard part of treatment protocols in stage II
and III rectal cancer. Compared to postoperative chemoradiotherapy, the advantage of
preoperative application of chemotherapeutics and irradiation includes improved compliance,
reduced toxicity, and downstaging of the tumor in a substantial number of patients. The
latter may enhance the rate of curative surgery, permit sphincter preservation in patients
with low-sited tumors, and have a positive impact on the quality of life of these patients
(Sauer et al, 2004).

The most widely used chemotherapeutic agent in colorectal cancer has been 5-fluorouracil
(5-FU), and numerous attempts have been made to improve its efficacy, including
biomodulation and protracted infusion. It has been demonstrated that biomodulation with
leucovorin or levamisole was not effective in rectal cancer (Tepper et al, 2002), and
protracted infusion of 5-FU was superior to bolus injection (O'Connell et al, 1994). New
oral chemotherapeutic agents including capecitabine have been introduced and tried in
colorectal cancer. Capecitabine is a tumor-selective fluoropyrimidine carbamate designed to
achieve a higher intratumoral 5-FU level with lower systemic toxicity than intravenous
administration of 5-FU (Shimma et al, 2000). It passes intact through the intestinal mucosa
and is converted to 5-FU, preferentially in tumor tissue by thymidine phosphorylase
(Schuller et al, 2000 ; Ishikawa et al, 1998 ; Miwa et al, 1998). Theoretically, oral
capecitabine mimics the effect of protracted infusion of 5-FU without complications
accompanying intravenous delivery (Liu et al, 1997). Moreover, experimental data using human
cancer xenografts demonstrated up-regulation of thymidine phosphorylase by radiation (Sawada
et al, 1999), constituting a synergistic effect. In two randomized Phase III trials,
capecitabine showed a superior overall response rate and safety profile compared with
5-FU/lecovorinin for metastatic colorectal cancer (Van Cutsem et al, 2001; Hoff et al, 2001;
Twelves, 2002). Intensity modulated radiotherapy (IMRT)-based radiation therapy that
delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause
less damage to normal tissue. (Ballonoff et al, 2008)

With such encouraging outcomes, investigators initiated a prospective study to evaluate the
efficacy and toxicity of short course preoperative chemoradiotherapy utilizing Intensity
Modulated Radiation Therapy (IMRT) in combination with capecitabine in patients with
resectable rectal carcinoma.

Inclusion Criteria:

- Pathologically confirmed diagnosis of adenocarcinoma of the rectum by biopsy
technique that does not completely excise the lesion (e.g., fine needle aspiration,
core needle biopsy)

- Located up to 15 cm from the anal verge with no extension of malignant disease into
the anal canal

- Stage IIIB-IIIC disease (T3-T4, N0-2, M0)(i.e., without evidence of distant
metastases) tumor as determined by the following assessments:Colonoscopy and biopsy
within the past 8 weeks; History/physical examination (including medication history
screen for contraindications) within the past 8 weeks; Contrast-enhanced imaging of
the abdomen and pelvis either by CT, MRI, or PET-CT (whole body preferred) within the
past 8 weeks

- Chest x-ray (or CT) of the chest within the past 8 weeks to exclude distant
metastases (except for patients who have had whole body PET-CT)

- Transrectal ultrasound (TRUS) within the past 8 weeks required to establish tumor

- TRUS not required if clinical exam, CT of the pelvis, and/or MRI demonstrates T4

- No synchronous primary colon carcinoma

- No evidence of distant metastases (M1)

- ANC ≥ 1,800/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve hemoglobin ≥ 8.0
g/dL allowed)

- AST < 2.5 times upper limit of normal (ULN)

- Alkaline phosphatase < 2.5 times ULN

- Bilirubin ≤ 1.5 times ULN

- Creatinine clearance > 50 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior invasive malignancy except nonmelanoma skin cancer unless disease free for a
minimum of 3 years

Exclusion Criteria:

- Severe, active comorbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within the
past 12 months

- Transmural myocardial infarction within the past 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within the past 30 days

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects


- Evidence of uncontrolled seizures, central nervous system disorders, or psychiatric
disability judged by the investigator to be clinically significant, precluding
informed consent, or interfering with compliance of oral drug intake

- Known, existing uncontrolled coagulopathy, unless clinically stable on
anticoagulation therapy for ≥ 2 weeks

- Evidence of peripheral neuropathy ≥ grade 2

- Prior allergic reaction to capecitabine

- Lack of physical integrity of the gastrointestinal tract (i.e., severe Crohn disease
that results in malabsorption; significant bowel resection that would make one
concerned about the absorption of capecitabine) or malabsorption syndrome that would
preclude feasibility of oral chemotherapy (i.e., capecitabine)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate if downstaging of tumor is observed after preoperative chemoradiotherapy: pathological T stage of disease in surgical specimen will be compared with preoperative T stage.

Outcome Time Frame:

Every 21 days

Safety Issue:


Principal Investigator

Weiguo Cao, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ruijin Hospital


China: Food and Drug Administration

Study ID:




Start Date:

July 2009

Completion Date:

July 2012

Related Keywords:

  • Chemoradiotherapy
  • Intensity Modulated Radiation Therapy
  • Capecitabine
  • Resectable Rectal Carcinoma
  • Carcinoma
  • Rectal Neoplasms